Roxanne Nelson, RN, BSN

Another survey has shown that Americans are largely unaware of the link between alcohol consumption and cancer.

The new findings, from a nationally representative survey that included responses from 3,865 adults, show a low awareness of the cancer risk from alcohol, and also that the risk varies by type of drink. Just under a third (31.2%) of respondents thought that consuming liquor/spirits was associated with a risk of cancer, but this fell to 24.9% for drinking beer and even further, to 20.3%, for drinking wine.

In fact, some respondents though the opposite – that drinking alcohol has health benefits; 10.3% of respondents thought that drinking wine was associated with a decreased cancer risk, while 2.25% thought the same for drinking beer, and 1.7% thought that for drinking liquor.

Most U.S. adults (> 50%) reported not knowing how these beverages affected cancer risk, the authors report.

“This study’s findings underscore the need to develop interventions for educating the public about the cancer risks of alcohol use, particularly in the prevailing context of national dialogue about the purported heart health benefits of wine,” commented senior author William M. P. Klein, PhD, associate director of the National Cancer Institute’s Behavioral Research Program, in a statement.

“All types of alcoholic beverages, including wine, increase cancer risk,” Dr. Klein said.

The findings were published online in Cancer Epidemiology, Biomarkers & Prevention.

The results echo the findings of a previous national survey that also found that the majority of Americans are not aware that alcohol consumption is associated with an increased risk of developing a variety of cancers.

In contrast, within the scientific community, there is long-standing and increasing awareness of alcohol consumption as a leading modifiable risk factor for cancer, and there is a growing movement calling for more public health awareness of the link.

Recently, there has been some public support for adding written warnings about the cancer risk from alcohol. A Citizen Petition was filed in 2021, and in August 2022, The New England Journal of Medicine issued a call for new labeling.

Several cancer organizations are petitioning for warnings to be added to alcoholic beverages. The petition is supported by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations. Proposed labeling would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

Dr. Klein and colleagues suggest that public health interventions, including mass media campaigns, cancer warning labels, and patient-provider communications, could help disseminate information about cancer and alcohol. “Educating the public about how alcohol increases cancer risk will not only empower consumers to make more informed decisions but may also prevent and reduce excessive alcohol use, as well as cancer morbidity and mortality,” Dr. Klein said.

The study was supported by the Division of Cancer Control and Population Sciences at the National Cancer Institute. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Another survey has shown that Americans are largely unaware of the link between alcohol consumption and cancer.

The new findings, from a nationally representative survey that included responses from 3,865 adults, show a low awareness of the cancer risk from alcohol, and also that the risk varies by type of drink. Just under a third (31.2%) of respondents thought that consuming liquor/spirits was associated with a risk of cancer, but this fell to 24.9% for drinking beer and even further, to 20.3%, for drinking wine.

In fact, some respondents though the opposite – that drinking alcohol has health benefits; 10.3% of respondents thought that drinking wine was associated with a decreased cancer risk, while 2.25% thought the same for drinking beer, and 1.7% thought that for drinking liquor.

Most U.S. adults (> 50%) reported not knowing how these beverages affected cancer risk, the authors report.

“This study’s findings underscore the need to develop interventions for educating the public about the cancer risks of alcohol use, particularly in the prevailing context of national dialogue about the purported heart health benefits of wine,” commented senior author William M. P. Klein, PhD, associate director of the National Cancer Institute’s Behavioral Research Program, in a statement.

“All types of alcoholic beverages, including wine, increase cancer risk,” Dr. Klein said.

The findings were published online in Cancer Epidemiology, Biomarkers & Prevention.

The results echo the findings of a previous national survey that also found that the majority of Americans are not aware that alcohol consumption is associated with an increased risk of developing a variety of cancers.

In contrast, within the scientific community, there is long-standing and increasing awareness of alcohol consumption as a leading modifiable risk factor for cancer, and there is a growing movement calling for more public health awareness of the link.

Recently, there has been some public support for adding written warnings about the cancer risk from alcohol. A Citizen Petition was filed in 2021, and in August 2022, The New England Journal of Medicine issued a call for new labeling.

Several cancer organizations are petitioning for warnings to be added to alcoholic beverages. The petition is supported by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations. Proposed labeling would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

Dr. Klein and colleagues suggest that public health interventions, including mass media campaigns, cancer warning labels, and patient-provider communications, could help disseminate information about cancer and alcohol. “Educating the public about how alcohol increases cancer risk will not only empower consumers to make more informed decisions but may also prevent and reduce excessive alcohol use, as well as cancer morbidity and mortality,” Dr. Klein said.

The study was supported by the Division of Cancer Control and Population Sciences at the National Cancer Institute. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Another survey has shown that Americans are largely unaware of the link between alcohol consumption and cancer.

The new findings, from a nationally representative survey that included responses from 3,865 adults, show a low awareness of the cancer risk from alcohol, and also that the risk varies by type of drink. Just under a third (31.2%) of respondents thought that consuming liquor/spirits was associated with a risk of cancer, but this fell to 24.9% for drinking beer and even further, to 20.3%, for drinking wine.

In fact, some respondents though the opposite – that drinking alcohol has health benefits; 10.3% of respondents thought that drinking wine was associated with a decreased cancer risk, while 2.25% thought the same for drinking beer, and 1.7% thought that for drinking liquor.

Most U.S. adults (> 50%) reported not knowing how these beverages affected cancer risk, the authors report.

“This study’s findings underscore the need to develop interventions for educating the public about the cancer risks of alcohol use, particularly in the prevailing context of national dialogue about the purported heart health benefits of wine,” commented senior author William M. P. Klein, PhD, associate director of the National Cancer Institute’s Behavioral Research Program, in a statement.

“All types of alcoholic beverages, including wine, increase cancer risk,” Dr. Klein said.

The findings were published online in Cancer Epidemiology, Biomarkers & Prevention.

The results echo the findings of a previous national survey that also found that the majority of Americans are not aware that alcohol consumption is associated with an increased risk of developing a variety of cancers.

In contrast, within the scientific community, there is long-standing and increasing awareness of alcohol consumption as a leading modifiable risk factor for cancer, and there is a growing movement calling for more public health awareness of the link.

Recently, there has been some public support for adding written warnings about the cancer risk from alcohol. A Citizen Petition was filed in 2021, and in August 2022, The New England Journal of Medicine issued a call for new labeling.

Several cancer organizations are petitioning for warnings to be added to alcoholic beverages. The petition is supported by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations. Proposed labeling would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

Dr. Klein and colleagues suggest that public health interventions, including mass media campaigns, cancer warning labels, and patient-provider communications, could help disseminate information about cancer and alcohol. “Educating the public about how alcohol increases cancer risk will not only empower consumers to make more informed decisions but may also prevent and reduce excessive alcohol use, as well as cancer morbidity and mortality,” Dr. Klein said.

The study was supported by the Division of Cancer Control and Population Sciences at the National Cancer Institute. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Individuals with a primary melanoma may be more likely to develop a second primary melanoma if they have certain characteristics, a new study suggests.

In a cohort study of more than 38,000 patients, those diagnosed with a second primary melanoma were significantly more likely to have a “nevus-prone” phenotype and a high polygenic risk score for melanoma.

Notably, the researchers also found only limited evidence that elevated levels of sun exposure contributed to second melanoma risk.

Overall, the findings suggest that “within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanoma,” Catherine M. Olsen, PhD, of the University of Queensland, Australia, and colleagues concluded.

The study was published online in JAMA Dermatology.

People with melanoma are believed to be at high risk for developing subsequent tumors, yet most never do. Population-based studies indicate that only about 8%-18% of patients are diagnosed with a second primary melanoma.

Previous studies using modified case-control design have identified several factors associated with developing multiple primary melanomas, including older age, male sex, a family history of melanoma, high nevus counts or presence of atypical nevi, higher ambient UV radiation and personal sun exposure, as well as certain inherited genetic variants.

However, these studies aren’t equipped to assess the magnitude of risk of developing multiple melanomas among those who have not yet had melanoma.

In the current analysis, Dr. Olsen and colleagues set out to understand the level of risk using a prospective cohort study design. The cohort comprised participants in the QSkin Sun and Health Study and included 38,845 patients with a baseline median age of 56 years, followed for a median of 7.4 years. Among these participants, 1,212 (3.1%) had only one primary melanoma diagnosis, and 245 (0.6%) had two or more primary melanomas. Of those with more primary melanomas, 59 had synchronous primary melanoma, meaning first and second primary melanomas were diagnosed on the same day.

The investigators compared the clinical characteristics of patients with first and second melanomas, looking at demographic, phenotypic, sun exposure, and genetic factors. The team found that the median time between first and second melanoma, excluding cases of synchronous primary melanoma, was 18.4 months.

Those who developed second melanomas were older at baseline than those who developed only one (59.3 years vs. 58.2 years, respectively; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for nonmelanoma skin cancers, and a high polygenic risk score for melanoma. Among people who developed second primary melanomas, the second melanomas were more likely to be in situ and of the lentigo maligna subtype.

Notably, factors including age, sex, sunburn tendency, and family history of melanoma had similarly elevated effect sizes among those diagnosed with first and second melanomas. The authors also found similar associations with baseline measures for personal sun exposure – including sunburns and cumulative sun exposure; however, the number of past skin cancer excisions was more strongly associated with second primaries (P = .05).

The team did identify two factors associated with a higher risk of developing a second primary melanoma. A nevus phenotype was more strongly associated with developing a second primary melanoma (hazard ratio, 6.36) than the initial one (HR, 3.46). And second primary melanomas had stronger associations with high melanoma polygenic risk scores than first primary melanomas (HR, 3.28 vs HR, 2.06; P = .03).

The authors noted several limitations to the study, including the generalizability of the findings outside of Australia and the relatively small number of people with second primary melanomas.

Still, the investigators note that the data “offer unique insights that differ from earlier efforts.” Namely, the “findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second [rather] than first primary melanomas.”

This work was supported by grants from the National Health and Medical Research Council of Australia. Dr. Olsen reports no relevant financial relationships. Coauthor Rachel Neale, PhD, reported grants from Viatris and the National Health and Medical Research Council of Australia outside the submitted work. Coauthor David Whiteman, MBBS, PhD, reported personal fees from Pierre Fabre (speaker fees for conference presentation) outside the submitted work. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

Individuals with a primary melanoma may be more likely to develop a second primary melanoma if they have certain characteristics, a new study suggests.

In a cohort study of more than 38,000 patients, those diagnosed with a second primary melanoma were significantly more likely to have a “nevus-prone” phenotype and a high polygenic risk score for melanoma.

Notably, the researchers also found only limited evidence that elevated levels of sun exposure contributed to second melanoma risk.

Overall, the findings suggest that “within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanoma,” Catherine M. Olsen, PhD, of the University of Queensland, Australia, and colleagues concluded.

The study was published online in JAMA Dermatology.

People with melanoma are believed to be at high risk for developing subsequent tumors, yet most never do. Population-based studies indicate that only about 8%-18% of patients are diagnosed with a second primary melanoma.

Previous studies using modified case-control design have identified several factors associated with developing multiple primary melanomas, including older age, male sex, a family history of melanoma, high nevus counts or presence of atypical nevi, higher ambient UV radiation and personal sun exposure, as well as certain inherited genetic variants.

However, these studies aren’t equipped to assess the magnitude of risk of developing multiple melanomas among those who have not yet had melanoma.

In the current analysis, Dr. Olsen and colleagues set out to understand the level of risk using a prospective cohort study design. The cohort comprised participants in the QSkin Sun and Health Study and included 38,845 patients with a baseline median age of 56 years, followed for a median of 7.4 years. Among these participants, 1,212 (3.1%) had only one primary melanoma diagnosis, and 245 (0.6%) had two or more primary melanomas. Of those with more primary melanomas, 59 had synchronous primary melanoma, meaning first and second primary melanomas were diagnosed on the same day.

The investigators compared the clinical characteristics of patients with first and second melanomas, looking at demographic, phenotypic, sun exposure, and genetic factors. The team found that the median time between first and second melanoma, excluding cases of synchronous primary melanoma, was 18.4 months.

Those who developed second melanomas were older at baseline than those who developed only one (59.3 years vs. 58.2 years, respectively; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for nonmelanoma skin cancers, and a high polygenic risk score for melanoma. Among people who developed second primary melanomas, the second melanomas were more likely to be in situ and of the lentigo maligna subtype.

Notably, factors including age, sex, sunburn tendency, and family history of melanoma had similarly elevated effect sizes among those diagnosed with first and second melanomas. The authors also found similar associations with baseline measures for personal sun exposure – including sunburns and cumulative sun exposure; however, the number of past skin cancer excisions was more strongly associated with second primaries (P = .05).

The team did identify two factors associated with a higher risk of developing a second primary melanoma. A nevus phenotype was more strongly associated with developing a second primary melanoma (hazard ratio, 6.36) than the initial one (HR, 3.46). And second primary melanomas had stronger associations with high melanoma polygenic risk scores than first primary melanomas (HR, 3.28 vs HR, 2.06; P = .03).

The authors noted several limitations to the study, including the generalizability of the findings outside of Australia and the relatively small number of people with second primary melanomas.

Still, the investigators note that the data “offer unique insights that differ from earlier efforts.” Namely, the “findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second [rather] than first primary melanomas.”

This work was supported by grants from the National Health and Medical Research Council of Australia. Dr. Olsen reports no relevant financial relationships. Coauthor Rachel Neale, PhD, reported grants from Viatris and the National Health and Medical Research Council of Australia outside the submitted work. Coauthor David Whiteman, MBBS, PhD, reported personal fees from Pierre Fabre (speaker fees for conference presentation) outside the submitted work. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

Individuals with a primary melanoma may be more likely to develop a second primary melanoma if they have certain characteristics, a new study suggests.

In a cohort study of more than 38,000 patients, those diagnosed with a second primary melanoma were significantly more likely to have a “nevus-prone” phenotype and a high polygenic risk score for melanoma.

Notably, the researchers also found only limited evidence that elevated levels of sun exposure contributed to second melanoma risk.

Overall, the findings suggest that “within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanoma,” Catherine M. Olsen, PhD, of the University of Queensland, Australia, and colleagues concluded.

The study was published online in JAMA Dermatology.

People with melanoma are believed to be at high risk for developing subsequent tumors, yet most never do. Population-based studies indicate that only about 8%-18% of patients are diagnosed with a second primary melanoma.

Previous studies using modified case-control design have identified several factors associated with developing multiple primary melanomas, including older age, male sex, a family history of melanoma, high nevus counts or presence of atypical nevi, higher ambient UV radiation and personal sun exposure, as well as certain inherited genetic variants.

However, these studies aren’t equipped to assess the magnitude of risk of developing multiple melanomas among those who have not yet had melanoma.

In the current analysis, Dr. Olsen and colleagues set out to understand the level of risk using a prospective cohort study design. The cohort comprised participants in the QSkin Sun and Health Study and included 38,845 patients with a baseline median age of 56 years, followed for a median of 7.4 years. Among these participants, 1,212 (3.1%) had only one primary melanoma diagnosis, and 245 (0.6%) had two or more primary melanomas. Of those with more primary melanomas, 59 had synchronous primary melanoma, meaning first and second primary melanomas were diagnosed on the same day.

The investigators compared the clinical characteristics of patients with first and second melanomas, looking at demographic, phenotypic, sun exposure, and genetic factors. The team found that the median time between first and second melanoma, excluding cases of synchronous primary melanoma, was 18.4 months.

Those who developed second melanomas were older at baseline than those who developed only one (59.3 years vs. 58.2 years, respectively; P < .001), and were more likely to have a sun-sensitive phenotype, a self-reported history of excisions for nonmelanoma skin cancers, and a high polygenic risk score for melanoma. Among people who developed second primary melanomas, the second melanomas were more likely to be in situ and of the lentigo maligna subtype.

Notably, factors including age, sex, sunburn tendency, and family history of melanoma had similarly elevated effect sizes among those diagnosed with first and second melanomas. The authors also found similar associations with baseline measures for personal sun exposure – including sunburns and cumulative sun exposure; however, the number of past skin cancer excisions was more strongly associated with second primaries (P = .05).

The team did identify two factors associated with a higher risk of developing a second primary melanoma. A nevus phenotype was more strongly associated with developing a second primary melanoma (hazard ratio, 6.36) than the initial one (HR, 3.46). And second primary melanomas had stronger associations with high melanoma polygenic risk scores than first primary melanomas (HR, 3.28 vs HR, 2.06; P = .03).

The authors noted several limitations to the study, including the generalizability of the findings outside of Australia and the relatively small number of people with second primary melanomas.

Still, the investigators note that the data “offer unique insights that differ from earlier efforts.” Namely, the “findings showed that many of the classic phenotypic risk factors for melanoma were similarly associated with risk of first and second melanomas; however, high numbers of nevi and high genetic predisposition were more strongly associated with second [rather] than first primary melanomas.”

This work was supported by grants from the National Health and Medical Research Council of Australia. Dr. Olsen reports no relevant financial relationships. Coauthor Rachel Neale, PhD, reported grants from Viatris and the National Health and Medical Research Council of Australia outside the submitted work. Coauthor David Whiteman, MBBS, PhD, reported personal fees from Pierre Fabre (speaker fees for conference presentation) outside the submitted work. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

A novel approach in which two products were co-administered achieved a 99% complete response rate in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (B-ALL).

In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.

The results showed that 192 of 194 patients (99%) achieved a complete remission.

The combined overall 12-month event-free survival was 73.5%.

The study was published online in the Journal of Clinical Oncology.

These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.

“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.

He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).

“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.

These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”

Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
 

Strategy of dual targeting

Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.

About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.

With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.

Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.

They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.
 

Achieved 99% remission

Dr. Pui and colleagues conducted a phase 2 trial that included 225 evaluable patients aged 20 years or younger who were being treated at five urban hospitals in and near Shanghai, China. Of this group, 194 had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

A safety run-in stage to determine the recommended dose was initially conducted. An interim analysis of the first 30 patients who were treated (27 at the recommended dose) showed that the approach was safe and effective. Additional patients were then enrolled.

The 192 patients (of 194) who achieved complete remission attained negative minimal residual disease status.

At a median follow-up of 11 months, 43 patients experienced relapse (24 with CD191/CD221 relapse, 16 with CD19– /CD221, one with CD19– /CD22– , and two unknown), for a cumulative risk of 22.2%.
 

Transplant and relapse options

In an interview, Dr. Pui noted that various treatment options were available for the children who experienced relapse. “For patients who were in good clinical condition, we will treat them with molecular therapeutics, allogeneic CAR T cells from donor, or even repeated humanized CD19 and/or CD22 CAR T cells with or without CD20 CAR T cells in an attempt to induce a remission for allogeneic transplantation,” he said.

The site-specific 12-month event-free survival rate in the trial was 69.2% for patients who did not receive a transplant, 95% for those children who had an isolated relapse to the testicles, and 68.6% for those who had an isolated central nervous system relapse.

After censoring 78 patients for consolidative transplantation, the 12-month overall survival was 87.7%.

Consolidative transplantation was performed in 24 of the 37 patients with KMT2A-rearranged or ZNF384-rearranged ALL and in 54 patients because of parental request. The reason for this was that patients with these two genetic subtypes of leukemia (KMT2A-rearranged and ZNF384-rearranged), under the pressure of phenotype-specific treatment (such as CAR T cells or blinatumomab) are at risk of lineage switch and development of secondary acute myeloid leukemia, explained Dr. Pui. “That is an even more resistant form of leukemia, and up to 5%-10% of the patients have been reported to develop this complication.

“We performed consolidation transplantation in these patients to avoid the risk of lineage switch but would accept the parental request not to perform allogeneic transplant after they were clearly informed of the risk,” he told this news organization.

He also suggested that this approach of co-administration of two types of CAR T cells would be especially suitable for “patients with extramedullary involvement, because most of them will be spared of local irradiation so that they can preserve their neurocognitive function and fertility and avoid radiation-induced second cancer, such as brain tumor,” he said.
 

Lower toxicity

With regard to toxicity, the majority of patients (n = 98, 88%) developed cytokine release syndrome, which was grade ≥3 in 64 (28.4%) patients and fatal in one. Neurotoxicity occurred in 47 (20.9%) patients, was of grade ≥3 in 9 (4.0%) patients, and was fatal in 2 patients who received 12 x 106 and 5.6 x 106 CAR T cells/kg.

In addition, grade 3 or 4 seizure developed in 14.2% of the patients; it was more common in those who had presented with isolated or combined CNS leukemia. Grade 3 or 4 hypotension occurred in 40.9% of the patients. About three-quarters of the patients were treated with tocilizumab (n = 67, 74.2%), and 79 (35.1%) were treated with corticosteroids.

“In general, CD19 and CD22 CAR T cells were less toxic than CD19 CAR T cells, the historical controls, in our experience,” said Dr. Pui. “There were three fatal complications, a rate not excessive considering a large number of patients were treated.”
 

Future studies needed

The researchers note that in this trial, the CD22 CAR T cells did not expand as robustly or persist as long as did the CD19 CAR T cells, and they hope that future studies will elucidate whether enhancing CD22 CAR T-cell persistence and activity would further improve outcomes.

The study was supported in part by the National Natural Science Foundation of China, the Shanghai Collaborative Innovation Center for Translational Medicine, the Research Programs of Shanghai Science, the Technology Commission Foundation, the U.S. National Cancer Institute, the VIVA China Children’s Cancer Foundation, and the American Lebanese Syrian Associated Charities.

A version of this article first appeared on Medscape.com.

A novel approach in which two products were co-administered achieved a 99% complete response rate in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (B-ALL).

In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.

The results showed that 192 of 194 patients (99%) achieved a complete remission.

The combined overall 12-month event-free survival was 73.5%.

The study was published online in the Journal of Clinical Oncology.

These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.

“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.

He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).

“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.

These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”

Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
 

Strategy of dual targeting

Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.

About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.

With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.

Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.

They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.
 

Achieved 99% remission

Dr. Pui and colleagues conducted a phase 2 trial that included 225 evaluable patients aged 20 years or younger who were being treated at five urban hospitals in and near Shanghai, China. Of this group, 194 had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

A safety run-in stage to determine the recommended dose was initially conducted. An interim analysis of the first 30 patients who were treated (27 at the recommended dose) showed that the approach was safe and effective. Additional patients were then enrolled.

The 192 patients (of 194) who achieved complete remission attained negative minimal residual disease status.

At a median follow-up of 11 months, 43 patients experienced relapse (24 with CD191/CD221 relapse, 16 with CD19– /CD221, one with CD19– /CD22– , and two unknown), for a cumulative risk of 22.2%.
 

Transplant and relapse options

In an interview, Dr. Pui noted that various treatment options were available for the children who experienced relapse. “For patients who were in good clinical condition, we will treat them with molecular therapeutics, allogeneic CAR T cells from donor, or even repeated humanized CD19 and/or CD22 CAR T cells with or without CD20 CAR T cells in an attempt to induce a remission for allogeneic transplantation,” he said.

The site-specific 12-month event-free survival rate in the trial was 69.2% for patients who did not receive a transplant, 95% for those children who had an isolated relapse to the testicles, and 68.6% for those who had an isolated central nervous system relapse.

After censoring 78 patients for consolidative transplantation, the 12-month overall survival was 87.7%.

Consolidative transplantation was performed in 24 of the 37 patients with KMT2A-rearranged or ZNF384-rearranged ALL and in 54 patients because of parental request. The reason for this was that patients with these two genetic subtypes of leukemia (KMT2A-rearranged and ZNF384-rearranged), under the pressure of phenotype-specific treatment (such as CAR T cells or blinatumomab) are at risk of lineage switch and development of secondary acute myeloid leukemia, explained Dr. Pui. “That is an even more resistant form of leukemia, and up to 5%-10% of the patients have been reported to develop this complication.

“We performed consolidation transplantation in these patients to avoid the risk of lineage switch but would accept the parental request not to perform allogeneic transplant after they were clearly informed of the risk,” he told this news organization.

He also suggested that this approach of co-administration of two types of CAR T cells would be especially suitable for “patients with extramedullary involvement, because most of them will be spared of local irradiation so that they can preserve their neurocognitive function and fertility and avoid radiation-induced second cancer, such as brain tumor,” he said.
 

Lower toxicity

With regard to toxicity, the majority of patients (n = 98, 88%) developed cytokine release syndrome, which was grade ≥3 in 64 (28.4%) patients and fatal in one. Neurotoxicity occurred in 47 (20.9%) patients, was of grade ≥3 in 9 (4.0%) patients, and was fatal in 2 patients who received 12 x 106 and 5.6 x 106 CAR T cells/kg.

In addition, grade 3 or 4 seizure developed in 14.2% of the patients; it was more common in those who had presented with isolated or combined CNS leukemia. Grade 3 or 4 hypotension occurred in 40.9% of the patients. About three-quarters of the patients were treated with tocilizumab (n = 67, 74.2%), and 79 (35.1%) were treated with corticosteroids.

“In general, CD19 and CD22 CAR T cells were less toxic than CD19 CAR T cells, the historical controls, in our experience,” said Dr. Pui. “There were three fatal complications, a rate not excessive considering a large number of patients were treated.”
 

Future studies needed

The researchers note that in this trial, the CD22 CAR T cells did not expand as robustly or persist as long as did the CD19 CAR T cells, and they hope that future studies will elucidate whether enhancing CD22 CAR T-cell persistence and activity would further improve outcomes.

The study was supported in part by the National Natural Science Foundation of China, the Shanghai Collaborative Innovation Center for Translational Medicine, the Research Programs of Shanghai Science, the Technology Commission Foundation, the U.S. National Cancer Institute, the VIVA China Children’s Cancer Foundation, and the American Lebanese Syrian Associated Charities.

A version of this article first appeared on Medscape.com.

A novel approach in which two products were co-administered achieved a 99% complete response rate in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (B-ALL).

In this trial, the largest study to date of a CAR T-cell therapy for such patients, the researchers co-administered two CAR T-cell therapies, one targeting CD19 and the other targeting CD22.

The results showed that 192 of 194 patients (99%) achieved a complete remission.

The combined overall 12-month event-free survival was 73.5%.

The study was published online in the Journal of Clinical Oncology.

These results are better than what has been reported for CAR T cells that are already on the market. These products, which target CD19, have achieved complete remission in 85.5% of cases and a 12-month event-free survival of 52.4% in children with B-ALL.

“We do believe [this approach] will become standard of care,” said study author Ching-Hon Pui, MD, of the departments of oncology, pathology, and global pediatric medicine, St. Jude Children’s Research Hospital, Memphis.

He noted that this work builds on the huge success that has already been achieved in this field with CAR T-cell products directed at CD19. The first of these products to reach the market was tisagenlecleucel-T (Novartis).

“To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones,” he said.

These new results are very impressive, said Stephen P. Hunger, MD, an expert commenting for the American Society of Clinical Oncology, which highlighted the research in a press release. “They were also able to treat almost 200 patients in a relatively short time.”

Hunger pointed out that dual administration and targeting is not a new idea and is one of the strategies that is currently under investigation. But it is too early to consider this to be the standard of care, he said. “We want to see it replicated in other centers and to see longer follow-up,” said Dr. Hunger, who is Distinguished Chair in Pediatrics and director of the center for childhood cancer research at Children’s Hospital of Philadelphia. “We can establish this as a first step down the road, and we will see if others will achieve similar results.”
 

Strategy of dual targeting

Despite the success CAR T-cell therapy in childhood leukemia, the currently available products have limitations, Dr. Pui and colleagues note.

About half of patients treated with CD19 CAR T cells experience relapse within 1 year, owing either to loss of CAR T-cell persistence or to loss of CD19 antigen because of splice variants, acquired genetic mutations, or lineage switch.

With further treatment with CAR T cells directed against CD22, 70%-80% of patients who failed CD19 CAR T will achieve into complete remission. However, most will experience relapse.

Recent efforts in the field have turned to exploring the safety and feasibility of CAR T cells that target both CD19 and CD22. The results were not superior to those of the CD19 CAR T-cell therapy given alone, although sequential treatment has yielded promising response rates, the authors note.

They hypothesized that co-administration of CD19- and CD22-targeted CAR T cells would improve efficacy, as it could forestall the development of drug resistance.
 

Achieved 99% remission

Dr. Pui and colleagues conducted a phase 2 trial that included 225 evaluable patients aged 20 years or younger who were being treated at five urban hospitals in and near Shanghai, China. Of this group, 194 had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

A safety run-in stage to determine the recommended dose was initially conducted. An interim analysis of the first 30 patients who were treated (27 at the recommended dose) showed that the approach was safe and effective. Additional patients were then enrolled.

The 192 patients (of 194) who achieved complete remission attained negative minimal residual disease status.

At a median follow-up of 11 months, 43 patients experienced relapse (24 with CD191/CD221 relapse, 16 with CD19– /CD221, one with CD19– /CD22– , and two unknown), for a cumulative risk of 22.2%.
 

Transplant and relapse options

In an interview, Dr. Pui noted that various treatment options were available for the children who experienced relapse. “For patients who were in good clinical condition, we will treat them with molecular therapeutics, allogeneic CAR T cells from donor, or even repeated humanized CD19 and/or CD22 CAR T cells with or without CD20 CAR T cells in an attempt to induce a remission for allogeneic transplantation,” he said.

The site-specific 12-month event-free survival rate in the trial was 69.2% for patients who did not receive a transplant, 95% for those children who had an isolated relapse to the testicles, and 68.6% for those who had an isolated central nervous system relapse.

After censoring 78 patients for consolidative transplantation, the 12-month overall survival was 87.7%.

Consolidative transplantation was performed in 24 of the 37 patients with KMT2A-rearranged or ZNF384-rearranged ALL and in 54 patients because of parental request. The reason for this was that patients with these two genetic subtypes of leukemia (KMT2A-rearranged and ZNF384-rearranged), under the pressure of phenotype-specific treatment (such as CAR T cells or blinatumomab) are at risk of lineage switch and development of secondary acute myeloid leukemia, explained Dr. Pui. “That is an even more resistant form of leukemia, and up to 5%-10% of the patients have been reported to develop this complication.

“We performed consolidation transplantation in these patients to avoid the risk of lineage switch but would accept the parental request not to perform allogeneic transplant after they were clearly informed of the risk,” he told this news organization.

He also suggested that this approach of co-administration of two types of CAR T cells would be especially suitable for “patients with extramedullary involvement, because most of them will be spared of local irradiation so that they can preserve their neurocognitive function and fertility and avoid radiation-induced second cancer, such as brain tumor,” he said.
 

Lower toxicity

With regard to toxicity, the majority of patients (n = 98, 88%) developed cytokine release syndrome, which was grade ≥3 in 64 (28.4%) patients and fatal in one. Neurotoxicity occurred in 47 (20.9%) patients, was of grade ≥3 in 9 (4.0%) patients, and was fatal in 2 patients who received 12 x 106 and 5.6 x 106 CAR T cells/kg.

In addition, grade 3 or 4 seizure developed in 14.2% of the patients; it was more common in those who had presented with isolated or combined CNS leukemia. Grade 3 or 4 hypotension occurred in 40.9% of the patients. About three-quarters of the patients were treated with tocilizumab (n = 67, 74.2%), and 79 (35.1%) were treated with corticosteroids.

“In general, CD19 and CD22 CAR T cells were less toxic than CD19 CAR T cells, the historical controls, in our experience,” said Dr. Pui. “There were three fatal complications, a rate not excessive considering a large number of patients were treated.”
 

Future studies needed

The researchers note that in this trial, the CD22 CAR T cells did not expand as robustly or persist as long as did the CD19 CAR T cells, and they hope that future studies will elucidate whether enhancing CD22 CAR T-cell persistence and activity would further improve outcomes.

The study was supported in part by the National Natural Science Foundation of China, the Shanghai Collaborative Innovation Center for Translational Medicine, the Research Programs of Shanghai Science, the Technology Commission Foundation, the U.S. National Cancer Institute, the VIVA China Children’s Cancer Foundation, and the American Lebanese Syrian Associated Charities.

A version of this article first appeared on Medscape.com.

PARIS – New results from a large prospective trial give a better idea of how a blood test that can detect multiple cancers performs in a “real-life” setting.

“As this technology develops, people must continue with their standard cancer screening, but this is a glimpse of what the future may hold,” commented study investigator Deborah Schrag, MD, MPH, chair, department of medicine, Memorial Sloan Kettering Cancer Center, New York.

For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals aged over 50, with or without additional cancer risk factors (such as history of smoking or genetic risk).

It found a positive cancer signal in 92 individuals (1.4%). 

None of the individuals who tested positive was known to have cancer at the time of testing. Subsequent workup, which could include scans and/or biopsy, found cancer in 38% of those with a positive test.

“When the test was positive, the workups were typically done in less than 3 months,” Dr. Schrag commented, adding that “the blood test typically predicted the origin of the cancer.”

Dr. Schrag presented the findings at the annual meeting of the European Society for Medical Oncology (ESMO).

Approached for comment, Anthony J. Olszanski, MD, RPh, vice chair of research at the Fox Chase Cancer Center, Philadelphia, noted that the use of a blood test to “find” cancer has long been on the minds of patients. “It is not uncommon to hear oncology patients ask: ‘Why didn’t my doctor find my cancer earlier, on blood tests?’ ”

As this study suggests, finding a malignancy before it becomes apparent on imaging or because of symptoms is one step closer to becoming a reality. “But although this is an important study, it must be noted that only about 40% of patients with a positive test result were actually found to have cancer,” Dr. Olszanski said. “Conversely, about 60% of patients with a positive test result likely suffered from a considerable amount of anxiety that may persist even after further testing did not reveal a malignancy.”

Another important issue is that such testing may incur substantial health care cost. “Less than 2 participants per 100 had a positive test result, and those patients underwent further testing to interrogate the result,” he added. “It also remains unclear if detecting cancer early will lead to better outcomes.”

Whether or not the test will be cost-effective remains unknown, as Dr. Schrag emphasized they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as the technology improves, costs will go down,” she said.

Dr. Schrag also added that this is a new concept and the trial shows it is feasible to detect cancer using a blood test. “It was not designed to determine if the test can decrease cancer mortality, which is obviously the purpose of screening, but it’s premature for that,” she said.
 

Details of the results

The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal across more than 50 cancer types as well as to predict cancer signal origin.

Overall, the test detected a cancer signal in 1.4% (n = 92) of participants with analyzable samples.

A total of 90 participants underwent diagnostic testing (33 true positives and 57 false positives). Of the true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.

Specificity was 99.1%, positive predictive value (PPV) was approximately 40%, and 73% of those who were true positives had diagnostic resolution in less than 3 months.

Of the cancers that were diagnosed, 19 were solid tumors and 17 were hematologic cancers; 7 were diagnosed in a person with a history of cancer, 26 were cancer types without standard screening, and 14 were diagnosed at an early stage.

“What is exciting about this new paradigm is that many of these were cancers for which we don’t have standard screening,” said Dr. Schrag.

Dr. Schrag noted that given the immense interest in this study, the manufacturer is working toward refining the assay and improving the test. A reanalysis was conducted on all specimens using a refined version of the test.

“Importantly, the new analysis identified fewer patients with having positive signals, from 1.4% to 0.9%,” she said. “Specificity improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened to find a cancer – up to 263 from 189.”
 

False positives concerning

Previous, and very similar, results from the PATHFINDER trial were presented last year at the annual meeting of the American Society of Clinical Oncology.

Max Diehn, MD, PhD, associate professor of radiation oncology at Stanford (Calif.) University, was an invited discussant for the study.

He pointed out that there were more false positives than true positives and noted that “there were a significant number of invasive procedures in false positives, which could cause harm to these patients who don’t have cancer.”

Dr. Diehn also explained that most true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphoid malignancy has clinical utility. 

The Galleri test is already available in the United States and is being offered by a number of U.S. health networks. However, it is not approved by the U.S. Food and Drug Administration and is not covered by medical insurance, so individuals have to pay around $950 for it out of pocket. 

Although some experts are excited by its potential, describing it as a “game-changer,” others are concerned that there are no clinical pathways in place yet to deal with the results of such a blood test, and say it is not ready for prime time. 

The study was funded by Grail, a subsidiary of Illumina. Dr. Shrag has reported relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several coauthors also have disclosed relationships with industry. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and Instil Bio, and running trials for them.

A version of this article first appeared on Medscape.com.

PARIS – New results from a large prospective trial give a better idea of how a blood test that can detect multiple cancers performs in a “real-life” setting.

“As this technology develops, people must continue with their standard cancer screening, but this is a glimpse of what the future may hold,” commented study investigator Deborah Schrag, MD, MPH, chair, department of medicine, Memorial Sloan Kettering Cancer Center, New York.

For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals aged over 50, with or without additional cancer risk factors (such as history of smoking or genetic risk).

It found a positive cancer signal in 92 individuals (1.4%). 

None of the individuals who tested positive was known to have cancer at the time of testing. Subsequent workup, which could include scans and/or biopsy, found cancer in 38% of those with a positive test.

“When the test was positive, the workups were typically done in less than 3 months,” Dr. Schrag commented, adding that “the blood test typically predicted the origin of the cancer.”

Dr. Schrag presented the findings at the annual meeting of the European Society for Medical Oncology (ESMO).

Approached for comment, Anthony J. Olszanski, MD, RPh, vice chair of research at the Fox Chase Cancer Center, Philadelphia, noted that the use of a blood test to “find” cancer has long been on the minds of patients. “It is not uncommon to hear oncology patients ask: ‘Why didn’t my doctor find my cancer earlier, on blood tests?’ ”

As this study suggests, finding a malignancy before it becomes apparent on imaging or because of symptoms is one step closer to becoming a reality. “But although this is an important study, it must be noted that only about 40% of patients with a positive test result were actually found to have cancer,” Dr. Olszanski said. “Conversely, about 60% of patients with a positive test result likely suffered from a considerable amount of anxiety that may persist even after further testing did not reveal a malignancy.”

Another important issue is that such testing may incur substantial health care cost. “Less than 2 participants per 100 had a positive test result, and those patients underwent further testing to interrogate the result,” he added. “It also remains unclear if detecting cancer early will lead to better outcomes.”

Whether or not the test will be cost-effective remains unknown, as Dr. Schrag emphasized they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as the technology improves, costs will go down,” she said.

Dr. Schrag also added that this is a new concept and the trial shows it is feasible to detect cancer using a blood test. “It was not designed to determine if the test can decrease cancer mortality, which is obviously the purpose of screening, but it’s premature for that,” she said.
 

Details of the results

The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal across more than 50 cancer types as well as to predict cancer signal origin.

Overall, the test detected a cancer signal in 1.4% (n = 92) of participants with analyzable samples.

A total of 90 participants underwent diagnostic testing (33 true positives and 57 false positives). Of the true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.

Specificity was 99.1%, positive predictive value (PPV) was approximately 40%, and 73% of those who were true positives had diagnostic resolution in less than 3 months.

Of the cancers that were diagnosed, 19 were solid tumors and 17 were hematologic cancers; 7 were diagnosed in a person with a history of cancer, 26 were cancer types without standard screening, and 14 were diagnosed at an early stage.

“What is exciting about this new paradigm is that many of these were cancers for which we don’t have standard screening,” said Dr. Schrag.

Dr. Schrag noted that given the immense interest in this study, the manufacturer is working toward refining the assay and improving the test. A reanalysis was conducted on all specimens using a refined version of the test.

“Importantly, the new analysis identified fewer patients with having positive signals, from 1.4% to 0.9%,” she said. “Specificity improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened to find a cancer – up to 263 from 189.”
 

False positives concerning

Previous, and very similar, results from the PATHFINDER trial were presented last year at the annual meeting of the American Society of Clinical Oncology.

Max Diehn, MD, PhD, associate professor of radiation oncology at Stanford (Calif.) University, was an invited discussant for the study.

He pointed out that there were more false positives than true positives and noted that “there were a significant number of invasive procedures in false positives, which could cause harm to these patients who don’t have cancer.”

Dr. Diehn also explained that most true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphoid malignancy has clinical utility. 

The Galleri test is already available in the United States and is being offered by a number of U.S. health networks. However, it is not approved by the U.S. Food and Drug Administration and is not covered by medical insurance, so individuals have to pay around $950 for it out of pocket. 

Although some experts are excited by its potential, describing it as a “game-changer,” others are concerned that there are no clinical pathways in place yet to deal with the results of such a blood test, and say it is not ready for prime time. 

The study was funded by Grail, a subsidiary of Illumina. Dr. Shrag has reported relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several coauthors also have disclosed relationships with industry. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and Instil Bio, and running trials for them.

A version of this article first appeared on Medscape.com.

PARIS – New results from a large prospective trial give a better idea of how a blood test that can detect multiple cancers performs in a “real-life” setting.

“As this technology develops, people must continue with their standard cancer screening, but this is a glimpse of what the future may hold,” commented study investigator Deborah Schrag, MD, MPH, chair, department of medicine, Memorial Sloan Kettering Cancer Center, New York.

For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals aged over 50, with or without additional cancer risk factors (such as history of smoking or genetic risk).

It found a positive cancer signal in 92 individuals (1.4%). 

None of the individuals who tested positive was known to have cancer at the time of testing. Subsequent workup, which could include scans and/or biopsy, found cancer in 38% of those with a positive test.

“When the test was positive, the workups were typically done in less than 3 months,” Dr. Schrag commented, adding that “the blood test typically predicted the origin of the cancer.”

Dr. Schrag presented the findings at the annual meeting of the European Society for Medical Oncology (ESMO).

Approached for comment, Anthony J. Olszanski, MD, RPh, vice chair of research at the Fox Chase Cancer Center, Philadelphia, noted that the use of a blood test to “find” cancer has long been on the minds of patients. “It is not uncommon to hear oncology patients ask: ‘Why didn’t my doctor find my cancer earlier, on blood tests?’ ”

As this study suggests, finding a malignancy before it becomes apparent on imaging or because of symptoms is one step closer to becoming a reality. “But although this is an important study, it must be noted that only about 40% of patients with a positive test result were actually found to have cancer,” Dr. Olszanski said. “Conversely, about 60% of patients with a positive test result likely suffered from a considerable amount of anxiety that may persist even after further testing did not reveal a malignancy.”

Another important issue is that such testing may incur substantial health care cost. “Less than 2 participants per 100 had a positive test result, and those patients underwent further testing to interrogate the result,” he added. “It also remains unclear if detecting cancer early will lead to better outcomes.”

Whether or not the test will be cost-effective remains unknown, as Dr. Schrag emphasized they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as the technology improves, costs will go down,” she said.

Dr. Schrag also added that this is a new concept and the trial shows it is feasible to detect cancer using a blood test. “It was not designed to determine if the test can decrease cancer mortality, which is obviously the purpose of screening, but it’s premature for that,” she said.
 

Details of the results

The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal across more than 50 cancer types as well as to predict cancer signal origin.

Overall, the test detected a cancer signal in 1.4% (n = 92) of participants with analyzable samples.

A total of 90 participants underwent diagnostic testing (33 true positives and 57 false positives). Of the true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.

Specificity was 99.1%, positive predictive value (PPV) was approximately 40%, and 73% of those who were true positives had diagnostic resolution in less than 3 months.

Of the cancers that were diagnosed, 19 were solid tumors and 17 were hematologic cancers; 7 were diagnosed in a person with a history of cancer, 26 were cancer types without standard screening, and 14 were diagnosed at an early stage.

“What is exciting about this new paradigm is that many of these were cancers for which we don’t have standard screening,” said Dr. Schrag.

Dr. Schrag noted that given the immense interest in this study, the manufacturer is working toward refining the assay and improving the test. A reanalysis was conducted on all specimens using a refined version of the test.

“Importantly, the new analysis identified fewer patients with having positive signals, from 1.4% to 0.9%,” she said. “Specificity improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened to find a cancer – up to 263 from 189.”
 

False positives concerning

Previous, and very similar, results from the PATHFINDER trial were presented last year at the annual meeting of the American Society of Clinical Oncology.

Max Diehn, MD, PhD, associate professor of radiation oncology at Stanford (Calif.) University, was an invited discussant for the study.

He pointed out that there were more false positives than true positives and noted that “there were a significant number of invasive procedures in false positives, which could cause harm to these patients who don’t have cancer.”

Dr. Diehn also explained that most true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphoid malignancy has clinical utility. 

The Galleri test is already available in the United States and is being offered by a number of U.S. health networks. However, it is not approved by the U.S. Food and Drug Administration and is not covered by medical insurance, so individuals have to pay around $950 for it out of pocket. 

Although some experts are excited by its potential, describing it as a “game-changer,” others are concerned that there are no clinical pathways in place yet to deal with the results of such a blood test, and say it is not ready for prime time. 

The study was funded by Grail, a subsidiary of Illumina. Dr. Shrag has reported relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several coauthors also have disclosed relationships with industry. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and Instil Bio, and running trials for them.

A version of this article first appeared on Medscape.com.

Warning labels on alcoholic products need to be updated to spell out details of potential harm in order to make them more effective, two U.S. researchers have said.

The current labeling, which has not changed for 30 years, focuses on risks during pregnancy and with operating machinery and includes a vague statement that alcohol “may cause health problems.”

This is “so understated that it borders on being misleading,” the two researchers argued.

The science related to the use of alcohol has moved on, and there is now firm evidence of harm. Alcohol has been classified by the International Agency for Research on Cancer (IARC)  as a group 1 carcinogen and has been linked to an increased risk of many types of cancer. Drinking alcohol has also been linked to a wide range of other diseases, from liver disease to pancreatitis to some types of heart disease, the authors noted.

Yet the general public is mostly unaware of the most serious health risks that are associated with alcohol consumption, they pointed out.

“We believe Americans deserve the opportunity to make well-informed decisions about their alcohol consumption,” said Anna H. Grummon, PhD, of the Harvard T. H. Chan School of Public Health, Boston, and Marissa G. Hall, PhD, of the University of North Carolina at Chapel Hill.

“Designing and adopting new alcohol warning labels should therefore be a research and policy priority,” they added.

The two researchers set out their arguments in a perspective article published in The New England Journal of Medicine.

“Alcohol consumption and its associated harms are reaching a crisis point in the United States,” they pointed out.

It now accounts for more than 140,000 deaths per year in the United States, according to the latest data from the Centers for Disease Control and Prevention. The COVID-19 pandemic has made the problem even worse – there was a 25% increase in alcohol-related deaths during 2020.

New, well-designed warning labels on alcohol is a common sense strategy for providing consumers with information and reducing the burden of alcohol-related harm, the authors suggested.
 

Warning Labels Prominently Displayed

Warning labels are most effective when they are prominently displayed, when they include pictures of some type, and when the messages alternate so as to avoid any one message from becoming “stale,” the authors noted. This approach has worked well with cigarette packs. This type of warning has increased smoking quit rates in comparison with smaller, side-of-pack, text-only warning labels.

There is some evidence that this type of labeling can be effective for alcohol. When large, pictorial warnings about cancer risk were temporarily added to the front of alcohol containers in some stores in Yukon, Canada, alcohol sales declined by 6%-10%, they pointed out.

However, pressure from the alcohol industry led to changes in the Yukon project, and while a general health warning remains, the label about increased cancer risk was removed.

The alcohol industry has tried to suppress efforts to educate the public, and this has created problems in conveying health information to consumers, the authors noted. The industry spends more than $1 billion each year to market its products in the United States.

The authors caution that without government intervention, the alcohol industry has little incentive to communicate the risks.

Some companies even link their products to health campaigns, such as selling pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast cancer research, despite compelling evidence linking alcohol to an increased risk of breast cancer.
 

Petition at Congress calling for new labels

This is not the first call for a change in the warning labels on alcohol.

Last year, a number of medical groups petitioned Congress for a new cancer-specific warning label to be displayed on all alcoholic beverages.

The petition was signed by the American Society of Clinical Oncology (ASCO), the American Institute for Cancer Research (AICR), and Breast Cancer Prevention Partners, in collaboration with the American Public Health Association, the Consumer Federation of America, the Center for Science in the Public Interest, Alcohol Justice, and the U.S. Alcohol Policy Alliance.

They are advocating for a label that would say: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

That petition is still pending, Melissa Maitin-Shepard, MPP, policy expert at the AICR, said in an interview.

In addition, the AICR is “working to advocate for the addition of a cancer warning label to alcoholic beverages through multiple channels,” she said. “Given the strong evidence linking alcohol use with at least six types of cancer – and low awareness of the alcohol and cancer connection – there is a tremendous need to educate the public about alcohol and cancer risk.”

Noelle K. LoConte, MD, associate professor of medicine at the University of Wisconsin, Madison, who is the lead author of ASCO’s statement on alcohol and cancer risk, emphasized that there is no doubt that alcohol is a carcinogen, that it causes about 5% of cancers globally, and that its use has increased during the pandemic.

“Initiatives that raise awareness around this issue could help generate more public support for policies that limit alcohol access and thereby decrease the number of alcohol-associated cancers,” she said. “In ASCO’s statement on alcohol and cancer, we recommend several key strategies to reduce high-risk alcohol consumption, including limiting youth access to alcohol, giving municipalities more control over alcohol outlet density and points of sale, and increasing taxes on alcohol.”

However, she also had a small criticism of one point in the NEJM article. It shows a sample infographic that lists gastric cancer as being caused by alcohol. “But as of today, gastric cancer is not on the IARC list of alcohol-associated cancers,” she said. “I think this brings to mind one critical point, that these warning labels have to contain scientifically established facts.”

Dr. Grummon and Dr. Hall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Warning labels on alcoholic products need to be updated to spell out details of potential harm in order to make them more effective, two U.S. researchers have said.

The current labeling, which has not changed for 30 years, focuses on risks during pregnancy and with operating machinery and includes a vague statement that alcohol “may cause health problems.”

This is “so understated that it borders on being misleading,” the two researchers argued.

The science related to the use of alcohol has moved on, and there is now firm evidence of harm. Alcohol has been classified by the International Agency for Research on Cancer (IARC)  as a group 1 carcinogen and has been linked to an increased risk of many types of cancer. Drinking alcohol has also been linked to a wide range of other diseases, from liver disease to pancreatitis to some types of heart disease, the authors noted.

Yet the general public is mostly unaware of the most serious health risks that are associated with alcohol consumption, they pointed out.

“We believe Americans deserve the opportunity to make well-informed decisions about their alcohol consumption,” said Anna H. Grummon, PhD, of the Harvard T. H. Chan School of Public Health, Boston, and Marissa G. Hall, PhD, of the University of North Carolina at Chapel Hill.

“Designing and adopting new alcohol warning labels should therefore be a research and policy priority,” they added.

The two researchers set out their arguments in a perspective article published in The New England Journal of Medicine.

“Alcohol consumption and its associated harms are reaching a crisis point in the United States,” they pointed out.

It now accounts for more than 140,000 deaths per year in the United States, according to the latest data from the Centers for Disease Control and Prevention. The COVID-19 pandemic has made the problem even worse – there was a 25% increase in alcohol-related deaths during 2020.

New, well-designed warning labels on alcohol is a common sense strategy for providing consumers with information and reducing the burden of alcohol-related harm, the authors suggested.
 

Warning Labels Prominently Displayed

Warning labels are most effective when they are prominently displayed, when they include pictures of some type, and when the messages alternate so as to avoid any one message from becoming “stale,” the authors noted. This approach has worked well with cigarette packs. This type of warning has increased smoking quit rates in comparison with smaller, side-of-pack, text-only warning labels.

There is some evidence that this type of labeling can be effective for alcohol. When large, pictorial warnings about cancer risk were temporarily added to the front of alcohol containers in some stores in Yukon, Canada, alcohol sales declined by 6%-10%, they pointed out.

However, pressure from the alcohol industry led to changes in the Yukon project, and while a general health warning remains, the label about increased cancer risk was removed.

The alcohol industry has tried to suppress efforts to educate the public, and this has created problems in conveying health information to consumers, the authors noted. The industry spends more than $1 billion each year to market its products in the United States.

The authors caution that without government intervention, the alcohol industry has little incentive to communicate the risks.

Some companies even link their products to health campaigns, such as selling pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast cancer research, despite compelling evidence linking alcohol to an increased risk of breast cancer.
 

Petition at Congress calling for new labels

This is not the first call for a change in the warning labels on alcohol.

Last year, a number of medical groups petitioned Congress for a new cancer-specific warning label to be displayed on all alcoholic beverages.

The petition was signed by the American Society of Clinical Oncology (ASCO), the American Institute for Cancer Research (AICR), and Breast Cancer Prevention Partners, in collaboration with the American Public Health Association, the Consumer Federation of America, the Center for Science in the Public Interest, Alcohol Justice, and the U.S. Alcohol Policy Alliance.

They are advocating for a label that would say: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

That petition is still pending, Melissa Maitin-Shepard, MPP, policy expert at the AICR, said in an interview.

In addition, the AICR is “working to advocate for the addition of a cancer warning label to alcoholic beverages through multiple channels,” she said. “Given the strong evidence linking alcohol use with at least six types of cancer – and low awareness of the alcohol and cancer connection – there is a tremendous need to educate the public about alcohol and cancer risk.”

Noelle K. LoConte, MD, associate professor of medicine at the University of Wisconsin, Madison, who is the lead author of ASCO’s statement on alcohol and cancer risk, emphasized that there is no doubt that alcohol is a carcinogen, that it causes about 5% of cancers globally, and that its use has increased during the pandemic.

“Initiatives that raise awareness around this issue could help generate more public support for policies that limit alcohol access and thereby decrease the number of alcohol-associated cancers,” she said. “In ASCO’s statement on alcohol and cancer, we recommend several key strategies to reduce high-risk alcohol consumption, including limiting youth access to alcohol, giving municipalities more control over alcohol outlet density and points of sale, and increasing taxes on alcohol.”

However, she also had a small criticism of one point in the NEJM article. It shows a sample infographic that lists gastric cancer as being caused by alcohol. “But as of today, gastric cancer is not on the IARC list of alcohol-associated cancers,” she said. “I think this brings to mind one critical point, that these warning labels have to contain scientifically established facts.”

Dr. Grummon and Dr. Hall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Warning labels on alcoholic products need to be updated to spell out details of potential harm in order to make them more effective, two U.S. researchers have said.

The current labeling, which has not changed for 30 years, focuses on risks during pregnancy and with operating machinery and includes a vague statement that alcohol “may cause health problems.”

This is “so understated that it borders on being misleading,” the two researchers argued.

The science related to the use of alcohol has moved on, and there is now firm evidence of harm. Alcohol has been classified by the International Agency for Research on Cancer (IARC)  as a group 1 carcinogen and has been linked to an increased risk of many types of cancer. Drinking alcohol has also been linked to a wide range of other diseases, from liver disease to pancreatitis to some types of heart disease, the authors noted.

Yet the general public is mostly unaware of the most serious health risks that are associated with alcohol consumption, they pointed out.

“We believe Americans deserve the opportunity to make well-informed decisions about their alcohol consumption,” said Anna H. Grummon, PhD, of the Harvard T. H. Chan School of Public Health, Boston, and Marissa G. Hall, PhD, of the University of North Carolina at Chapel Hill.

“Designing and adopting new alcohol warning labels should therefore be a research and policy priority,” they added.

The two researchers set out their arguments in a perspective article published in The New England Journal of Medicine.

“Alcohol consumption and its associated harms are reaching a crisis point in the United States,” they pointed out.

It now accounts for more than 140,000 deaths per year in the United States, according to the latest data from the Centers for Disease Control and Prevention. The COVID-19 pandemic has made the problem even worse – there was a 25% increase in alcohol-related deaths during 2020.

New, well-designed warning labels on alcohol is a common sense strategy for providing consumers with information and reducing the burden of alcohol-related harm, the authors suggested.
 

Warning Labels Prominently Displayed

Warning labels are most effective when they are prominently displayed, when they include pictures of some type, and when the messages alternate so as to avoid any one message from becoming “stale,” the authors noted. This approach has worked well with cigarette packs. This type of warning has increased smoking quit rates in comparison with smaller, side-of-pack, text-only warning labels.

There is some evidence that this type of labeling can be effective for alcohol. When large, pictorial warnings about cancer risk were temporarily added to the front of alcohol containers in some stores in Yukon, Canada, alcohol sales declined by 6%-10%, they pointed out.

However, pressure from the alcohol industry led to changes in the Yukon project, and while a general health warning remains, the label about increased cancer risk was removed.

The alcohol industry has tried to suppress efforts to educate the public, and this has created problems in conveying health information to consumers, the authors noted. The industry spends more than $1 billion each year to market its products in the United States.

The authors caution that without government intervention, the alcohol industry has little incentive to communicate the risks.

Some companies even link their products to health campaigns, such as selling pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast cancer research, despite compelling evidence linking alcohol to an increased risk of breast cancer.
 

Petition at Congress calling for new labels

This is not the first call for a change in the warning labels on alcohol.

Last year, a number of medical groups petitioned Congress for a new cancer-specific warning label to be displayed on all alcoholic beverages.

The petition was signed by the American Society of Clinical Oncology (ASCO), the American Institute for Cancer Research (AICR), and Breast Cancer Prevention Partners, in collaboration with the American Public Health Association, the Consumer Federation of America, the Center for Science in the Public Interest, Alcohol Justice, and the U.S. Alcohol Policy Alliance.

They are advocating for a label that would say: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

That petition is still pending, Melissa Maitin-Shepard, MPP, policy expert at the AICR, said in an interview.

In addition, the AICR is “working to advocate for the addition of a cancer warning label to alcoholic beverages through multiple channels,” she said. “Given the strong evidence linking alcohol use with at least six types of cancer – and low awareness of the alcohol and cancer connection – there is a tremendous need to educate the public about alcohol and cancer risk.”

Noelle K. LoConte, MD, associate professor of medicine at the University of Wisconsin, Madison, who is the lead author of ASCO’s statement on alcohol and cancer risk, emphasized that there is no doubt that alcohol is a carcinogen, that it causes about 5% of cancers globally, and that its use has increased during the pandemic.

“Initiatives that raise awareness around this issue could help generate more public support for policies that limit alcohol access and thereby decrease the number of alcohol-associated cancers,” she said. “In ASCO’s statement on alcohol and cancer, we recommend several key strategies to reduce high-risk alcohol consumption, including limiting youth access to alcohol, giving municipalities more control over alcohol outlet density and points of sale, and increasing taxes on alcohol.”

However, she also had a small criticism of one point in the NEJM article. It shows a sample infographic that lists gastric cancer as being caused by alcohol. “But as of today, gastric cancer is not on the IARC list of alcohol-associated cancers,” she said. “I think this brings to mind one critical point, that these warning labels have to contain scientifically established facts.”

Dr. Grummon and Dr. Hall have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The field of radiation oncology has rapidly evolved in recent years, thanks in large part to findings from randomized clinical trials (RCTs) that have helped shift therapeutic standards, a review of the literature shows.

The authors assessed all RCTs involving radiotherapy from 2018 to 2021, with the goal of identifying the latest practice-changing data, emerging concepts, and areas that require further study.

Highlights from this research reveal how high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, has improved care for many patients, how personalized radiotherapy using image-based guidance has helped tailor treatments, and how endpoints that focus on quality of life and patient satisfaction are emerging.

For instance, Charles B. Simone II, MD, FACRO, who was not involved in the current work, pointed to “a proliferation of trials assessing hypofractionation in the curative setting and stereotactic body radiation therapy in the curative and poly- and oligometastatic settings that have allowed for increased patient convenience and dose intensification, respectively.”

Dr. Simone, chief medical officer, New York Proton Center, Memorial Sloan Kettering Cancer Center, also noted that the first personalized radiotherapy trials using imaging and biological markers have “the profound potential to individualize treatment and improve patient outcomes.”

The review was published in the European Journal of Cancer.
 

An evolving field

Given the fast-changing landscape for cancer therapeutics and a deluge of research studies, the authors wanted to understand the most notable advances established in recent trials as well as caveats to some approaches and emerging areas to watch.

In the review, Sophie Espenel, MD, from the department of radiation oncology, Gustave Roussy Cancer Campus, Villejuif, France, and colleagues identified 1,347 radiotherapy RCTs that were conducted from January 2018 to December 2021. Of these, the authors selected 110 large phase 2 or 3 RCTs that contained data showing practice-changing or emerging concepts.

Overall, the studies showed “great dynamism” in radiation oncology research and covered a wide range of radiotherapy practices, according to Dr. Espenel and coauthors.

A central area of research has focused on radioimmunotherapy, an approach that aims to enhance the antitumor immune response. One RCT in the preoperative setting showed, for instance, that concurrent stereotactic body radiotherapy delivered at 24 Gy over eight fractions, along with the anti–PD-L1 agent durvalumab, increased major pathologic complete response rates almost eightfold in comparison with durvalumab alone for patients with early-stage lung cancer (53.3% vs. 6.7%).

Although promising, not all trials that evaluated a concurrent chemoradiotherapy-immunotherapy strategy showed positive results. One RCT of locally advanced head and neck squamous cell carcinoma, for instance, found that median progression-free survival was not reached when adding the anti–PD-L1 avelumab to chemoradiotherapy. In addition, trials in the metastatic setting have shown conflicting results, the authors note.

Another topic of interest is that of newer radiosensitizers. A trial that evaluated high-risk locoregionally advanced head and neck squamous cell carcinoma highlighted the efficacy of xevinapant, a pro-apoptotic agent that inhibits apoptosis proteins. Xevinapant was used for the first time in conjunction with a standard high-dose cisplatin chemoradiotherapy. In this study, locoregional control at 18 months was achieved for 54% of patients who received xevinapant vs. 33% of those who received standard care. The toxicity profiles were similar.

The use of high-tech radiotherapy is gaining ground. It allows patients to receive more targeted treatments at lower doses and in shorter time frames. One trial found, for instance, that a more hypofractionated adjuvant whole breast approach, using 26 Gy in five fractions over a week, is as effective and safe as 40 Gy in 15 fractions over 3 weeks. The researchers found that there was no difference in the incidence of locoregional relapses, disease-free survival, and overall survival between the regimens.

Dr. Simone also noted that advanced treatment modalities, such as intensity-modulated radiotherapy, stereotactic radiosurgery, and proton therapy, have the potential to improve patient-reported adverse events and clinical outcomes. “I have seen this both in my clinical practice and in several recent publications,” he says.

Personalization of radiotherapy is also an emerging area that may allow for more tailored treatments with improved outcomes. The authors highlighted a study that found that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach was also less expensive and led to less radiation exposure.

On the basis of this research, “PMSA PET-CT has since become the [standard of care] for prostate cancer staging,” the authors explain.

Dr. Espenel and colleagues note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming endpoints in RCTs. Experts are focusing more attention on sequelae of treatments and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is becoming increasingly possible in many cases as well. For example, with some clinical trials that involved different treatment modalities, outcomes were equivalent, but toxicity profiles differed, allowing patients to choose therapeutic options tailored to their preferences.

Overall, these data demonstrate “a great dynamism of radiation oncology research in most primary tumor types,” the researchers write.

The study received no outside financial support. The authors have disclosed no relevant financial relationships. Dr. Simone is chair of the American Society for Radiation Oncology Lung Resource Panel and the American Society for Radiation Oncology Veteran Affairs Radiation Oncology Quality Surveillance Blue Ribbon Lung Panel and has received honorarium from Varian Medical Systems.

A version of this article first appeared on Medscape.com.

The field of radiation oncology has rapidly evolved in recent years, thanks in large part to findings from randomized clinical trials (RCTs) that have helped shift therapeutic standards, a review of the literature shows.

The authors assessed all RCTs involving radiotherapy from 2018 to 2021, with the goal of identifying the latest practice-changing data, emerging concepts, and areas that require further study.

Highlights from this research reveal how high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, has improved care for many patients, how personalized radiotherapy using image-based guidance has helped tailor treatments, and how endpoints that focus on quality of life and patient satisfaction are emerging.

For instance, Charles B. Simone II, MD, FACRO, who was not involved in the current work, pointed to “a proliferation of trials assessing hypofractionation in the curative setting and stereotactic body radiation therapy in the curative and poly- and oligometastatic settings that have allowed for increased patient convenience and dose intensification, respectively.”

Dr. Simone, chief medical officer, New York Proton Center, Memorial Sloan Kettering Cancer Center, also noted that the first personalized radiotherapy trials using imaging and biological markers have “the profound potential to individualize treatment and improve patient outcomes.”

The review was published in the European Journal of Cancer.
 

An evolving field

Given the fast-changing landscape for cancer therapeutics and a deluge of research studies, the authors wanted to understand the most notable advances established in recent trials as well as caveats to some approaches and emerging areas to watch.

In the review, Sophie Espenel, MD, from the department of radiation oncology, Gustave Roussy Cancer Campus, Villejuif, France, and colleagues identified 1,347 radiotherapy RCTs that were conducted from January 2018 to December 2021. Of these, the authors selected 110 large phase 2 or 3 RCTs that contained data showing practice-changing or emerging concepts.

Overall, the studies showed “great dynamism” in radiation oncology research and covered a wide range of radiotherapy practices, according to Dr. Espenel and coauthors.

A central area of research has focused on radioimmunotherapy, an approach that aims to enhance the antitumor immune response. One RCT in the preoperative setting showed, for instance, that concurrent stereotactic body radiotherapy delivered at 24 Gy over eight fractions, along with the anti–PD-L1 agent durvalumab, increased major pathologic complete response rates almost eightfold in comparison with durvalumab alone for patients with early-stage lung cancer (53.3% vs. 6.7%).

Although promising, not all trials that evaluated a concurrent chemoradiotherapy-immunotherapy strategy showed positive results. One RCT of locally advanced head and neck squamous cell carcinoma, for instance, found that median progression-free survival was not reached when adding the anti–PD-L1 avelumab to chemoradiotherapy. In addition, trials in the metastatic setting have shown conflicting results, the authors note.

Another topic of interest is that of newer radiosensitizers. A trial that evaluated high-risk locoregionally advanced head and neck squamous cell carcinoma highlighted the efficacy of xevinapant, a pro-apoptotic agent that inhibits apoptosis proteins. Xevinapant was used for the first time in conjunction with a standard high-dose cisplatin chemoradiotherapy. In this study, locoregional control at 18 months was achieved for 54% of patients who received xevinapant vs. 33% of those who received standard care. The toxicity profiles were similar.

The use of high-tech radiotherapy is gaining ground. It allows patients to receive more targeted treatments at lower doses and in shorter time frames. One trial found, for instance, that a more hypofractionated adjuvant whole breast approach, using 26 Gy in five fractions over a week, is as effective and safe as 40 Gy in 15 fractions over 3 weeks. The researchers found that there was no difference in the incidence of locoregional relapses, disease-free survival, and overall survival between the regimens.

Dr. Simone also noted that advanced treatment modalities, such as intensity-modulated radiotherapy, stereotactic radiosurgery, and proton therapy, have the potential to improve patient-reported adverse events and clinical outcomes. “I have seen this both in my clinical practice and in several recent publications,” he says.

Personalization of radiotherapy is also an emerging area that may allow for more tailored treatments with improved outcomes. The authors highlighted a study that found that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach was also less expensive and led to less radiation exposure.

On the basis of this research, “PMSA PET-CT has since become the [standard of care] for prostate cancer staging,” the authors explain.

Dr. Espenel and colleagues note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming endpoints in RCTs. Experts are focusing more attention on sequelae of treatments and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is becoming increasingly possible in many cases as well. For example, with some clinical trials that involved different treatment modalities, outcomes were equivalent, but toxicity profiles differed, allowing patients to choose therapeutic options tailored to their preferences.

Overall, these data demonstrate “a great dynamism of radiation oncology research in most primary tumor types,” the researchers write.

The study received no outside financial support. The authors have disclosed no relevant financial relationships. Dr. Simone is chair of the American Society for Radiation Oncology Lung Resource Panel and the American Society for Radiation Oncology Veteran Affairs Radiation Oncology Quality Surveillance Blue Ribbon Lung Panel and has received honorarium from Varian Medical Systems.

A version of this article first appeared on Medscape.com.

The field of radiation oncology has rapidly evolved in recent years, thanks in large part to findings from randomized clinical trials (RCTs) that have helped shift therapeutic standards, a review of the literature shows.

The authors assessed all RCTs involving radiotherapy from 2018 to 2021, with the goal of identifying the latest practice-changing data, emerging concepts, and areas that require further study.

Highlights from this research reveal how high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, has improved care for many patients, how personalized radiotherapy using image-based guidance has helped tailor treatments, and how endpoints that focus on quality of life and patient satisfaction are emerging.

For instance, Charles B. Simone II, MD, FACRO, who was not involved in the current work, pointed to “a proliferation of trials assessing hypofractionation in the curative setting and stereotactic body radiation therapy in the curative and poly- and oligometastatic settings that have allowed for increased patient convenience and dose intensification, respectively.”

Dr. Simone, chief medical officer, New York Proton Center, Memorial Sloan Kettering Cancer Center, also noted that the first personalized radiotherapy trials using imaging and biological markers have “the profound potential to individualize treatment and improve patient outcomes.”

The review was published in the European Journal of Cancer.
 

An evolving field

Given the fast-changing landscape for cancer therapeutics and a deluge of research studies, the authors wanted to understand the most notable advances established in recent trials as well as caveats to some approaches and emerging areas to watch.

In the review, Sophie Espenel, MD, from the department of radiation oncology, Gustave Roussy Cancer Campus, Villejuif, France, and colleagues identified 1,347 radiotherapy RCTs that were conducted from January 2018 to December 2021. Of these, the authors selected 110 large phase 2 or 3 RCTs that contained data showing practice-changing or emerging concepts.

Overall, the studies showed “great dynamism” in radiation oncology research and covered a wide range of radiotherapy practices, according to Dr. Espenel and coauthors.

A central area of research has focused on radioimmunotherapy, an approach that aims to enhance the antitumor immune response. One RCT in the preoperative setting showed, for instance, that concurrent stereotactic body radiotherapy delivered at 24 Gy over eight fractions, along with the anti–PD-L1 agent durvalumab, increased major pathologic complete response rates almost eightfold in comparison with durvalumab alone for patients with early-stage lung cancer (53.3% vs. 6.7%).

Although promising, not all trials that evaluated a concurrent chemoradiotherapy-immunotherapy strategy showed positive results. One RCT of locally advanced head and neck squamous cell carcinoma, for instance, found that median progression-free survival was not reached when adding the anti–PD-L1 avelumab to chemoradiotherapy. In addition, trials in the metastatic setting have shown conflicting results, the authors note.

Another topic of interest is that of newer radiosensitizers. A trial that evaluated high-risk locoregionally advanced head and neck squamous cell carcinoma highlighted the efficacy of xevinapant, a pro-apoptotic agent that inhibits apoptosis proteins. Xevinapant was used for the first time in conjunction with a standard high-dose cisplatin chemoradiotherapy. In this study, locoregional control at 18 months was achieved for 54% of patients who received xevinapant vs. 33% of those who received standard care. The toxicity profiles were similar.

The use of high-tech radiotherapy is gaining ground. It allows patients to receive more targeted treatments at lower doses and in shorter time frames. One trial found, for instance, that a more hypofractionated adjuvant whole breast approach, using 26 Gy in five fractions over a week, is as effective and safe as 40 Gy in 15 fractions over 3 weeks. The researchers found that there was no difference in the incidence of locoregional relapses, disease-free survival, and overall survival between the regimens.

Dr. Simone also noted that advanced treatment modalities, such as intensity-modulated radiotherapy, stereotactic radiosurgery, and proton therapy, have the potential to improve patient-reported adverse events and clinical outcomes. “I have seen this both in my clinical practice and in several recent publications,” he says.

Personalization of radiotherapy is also an emerging area that may allow for more tailored treatments with improved outcomes. The authors highlighted a study that found that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach was also less expensive and led to less radiation exposure.

On the basis of this research, “PMSA PET-CT has since become the [standard of care] for prostate cancer staging,” the authors explain.

Dr. Espenel and colleagues note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming endpoints in RCTs. Experts are focusing more attention on sequelae of treatments and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is becoming increasingly possible in many cases as well. For example, with some clinical trials that involved different treatment modalities, outcomes were equivalent, but toxicity profiles differed, allowing patients to choose therapeutic options tailored to their preferences.

Overall, these data demonstrate “a great dynamism of radiation oncology research in most primary tumor types,” the researchers write.

The study received no outside financial support. The authors have disclosed no relevant financial relationships. Dr. Simone is chair of the American Society for Radiation Oncology Lung Resource Panel and the American Society for Radiation Oncology Veteran Affairs Radiation Oncology Quality Surveillance Blue Ribbon Lung Panel and has received honorarium from Varian Medical Systems.

A version of this article first appeared on Medscape.com.

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

A version of this article first appeared on Medscape.com.

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

A version of this article first appeared on Medscape.com.

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

A version of this article first appeared on Medscape.com.

The World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).

From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.

This could be a “game-changer for the prevention of the disease,” as it would allow “more doses of the life-saving jab reach more girls,” the WHO declared in a press release.

SAGE recommends updating HPV dose schedules as follows:

• One- or two-dose schedule for the primary target of girls aged 9-14 years.
• One- or two-dose schedule for young women aged 15-20.
• Two doses with a 6-month interval for women older than 21.

The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.

“SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes,” he added.

For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the advisory group noted.
 

Policy makers need to make changes

Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policy makers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.

“Policy makers should consider modifying their HPV immunization schedules for girls aged 9-14 years from a two-dose regimen to a one-dose regimen,” wrote Jeff D’Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ont., and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.

Policy makers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.

The editorialists also make a radical proposal.

Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).

To overcome these problems, they suggest that “high-income countries that currently offer two-dose regimens to girls aged 9-14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them.”
 

Two doses in high-income countries

But it is unclear whether high-income countries are ready to move to a one-dose schedule.

Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, told this news organization that while he can’t say for certain, he suspects that the United States will be slower to accept this recommendation for a single dose of HPV vaccine “as a component of a ‘standard-of-care’ approach.”

However, it “might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.

“I do not know if regulatory bodies in the United States will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country,” he said. “The issue would be that if a single dose was stated to be a clinically acceptable option in the United States, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort.”

Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, New York, said: “In higher-resourced countries, two doses are still preferred, as they are more effective than one.

“The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies,” she added.

At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.

Studies have shown that two doses of HPV vaccine given to children aged 9-14 years provide as good or better protection than three doses given to older adolescents or young adults.

But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.

Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
 

Trials of one-dose schedules

The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.

The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers noted.

A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.

Commenting on this trial in India in a recent interview with this news organization, Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need “to be confirmed by other studies.” The results were nonetheless “excellent news for developing countries where there are challenges when it comes to access to vaccination.”

Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases, he emphasized that at this stage, the findings “cannot be extrapolated” to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
 

Ethics of the vaccine

In their editorial, Dr. D’Souza and Dr. Nderitu note that there are ethical considerations with the HPV vaccine that can “help guide deliberations, covering nonmaleficence, beneficence, health equity, stewardship, and solidarity.”

It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9-14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. “When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind,” they say.

To achieve the goal of eliminating cervical cancer, “countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care,” they write. “Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals.”

Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9-14 years, as well as using additional resources to close the gap in these other areas.

Dr. Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. Dr. D’Souza and Dr. Nderitu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).

From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.

This could be a “game-changer for the prevention of the disease,” as it would allow “more doses of the life-saving jab reach more girls,” the WHO declared in a press release.

SAGE recommends updating HPV dose schedules as follows:

• One- or two-dose schedule for the primary target of girls aged 9-14 years.
• One- or two-dose schedule for young women aged 15-20.
• Two doses with a 6-month interval for women older than 21.

The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.

“SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes,” he added.

For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the advisory group noted.
 

Policy makers need to make changes

Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policy makers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.

“Policy makers should consider modifying their HPV immunization schedules for girls aged 9-14 years from a two-dose regimen to a one-dose regimen,” wrote Jeff D’Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ont., and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.

Policy makers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.

The editorialists also make a radical proposal.

Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).

To overcome these problems, they suggest that “high-income countries that currently offer two-dose regimens to girls aged 9-14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them.”
 

Two doses in high-income countries

But it is unclear whether high-income countries are ready to move to a one-dose schedule.

Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, told this news organization that while he can’t say for certain, he suspects that the United States will be slower to accept this recommendation for a single dose of HPV vaccine “as a component of a ‘standard-of-care’ approach.”

However, it “might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.

“I do not know if regulatory bodies in the United States will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country,” he said. “The issue would be that if a single dose was stated to be a clinically acceptable option in the United States, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort.”

Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, New York, said: “In higher-resourced countries, two doses are still preferred, as they are more effective than one.

“The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies,” she added.

At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.

Studies have shown that two doses of HPV vaccine given to children aged 9-14 years provide as good or better protection than three doses given to older adolescents or young adults.

But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.

Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
 

Trials of one-dose schedules

The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.

The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers noted.

A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.

Commenting on this trial in India in a recent interview with this news organization, Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need “to be confirmed by other studies.” The results were nonetheless “excellent news for developing countries where there are challenges when it comes to access to vaccination.”

Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases, he emphasized that at this stage, the findings “cannot be extrapolated” to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
 

Ethics of the vaccine

In their editorial, Dr. D’Souza and Dr. Nderitu note that there are ethical considerations with the HPV vaccine that can “help guide deliberations, covering nonmaleficence, beneficence, health equity, stewardship, and solidarity.”

It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9-14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. “When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind,” they say.

To achieve the goal of eliminating cervical cancer, “countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care,” they write. “Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals.”

Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9-14 years, as well as using additional resources to close the gap in these other areas.

Dr. Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. Dr. D’Souza and Dr. Nderitu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).

From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.

This could be a “game-changer for the prevention of the disease,” as it would allow “more doses of the life-saving jab reach more girls,” the WHO declared in a press release.

SAGE recommends updating HPV dose schedules as follows:

• One- or two-dose schedule for the primary target of girls aged 9-14 years.
• One- or two-dose schedule for young women aged 15-20.
• Two doses with a 6-month interval for women older than 21.

The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.

“SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes,” he added.

For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the advisory group noted.
 

Policy makers need to make changes

Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policy makers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.

“Policy makers should consider modifying their HPV immunization schedules for girls aged 9-14 years from a two-dose regimen to a one-dose regimen,” wrote Jeff D’Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ont., and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.

Policy makers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.

The editorialists also make a radical proposal.

Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).

To overcome these problems, they suggest that “high-income countries that currently offer two-dose regimens to girls aged 9-14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them.”
 

Two doses in high-income countries

But it is unclear whether high-income countries are ready to move to a one-dose schedule.

Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, told this news organization that while he can’t say for certain, he suspects that the United States will be slower to accept this recommendation for a single dose of HPV vaccine “as a component of a ‘standard-of-care’ approach.”

However, it “might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.

“I do not know if regulatory bodies in the United States will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country,” he said. “The issue would be that if a single dose was stated to be a clinically acceptable option in the United States, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort.”

Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, New York, said: “In higher-resourced countries, two doses are still preferred, as they are more effective than one.

“The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies,” she added.

At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.

Studies have shown that two doses of HPV vaccine given to children aged 9-14 years provide as good or better protection than three doses given to older adolescents or young adults.

But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.

Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
 

Trials of one-dose schedules

The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.

The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers noted.

A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.

Commenting on this trial in India in a recent interview with this news organization, Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need “to be confirmed by other studies.” The results were nonetheless “excellent news for developing countries where there are challenges when it comes to access to vaccination.”

Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases, he emphasized that at this stage, the findings “cannot be extrapolated” to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
 

Ethics of the vaccine

In their editorial, Dr. D’Souza and Dr. Nderitu note that there are ethical considerations with the HPV vaccine that can “help guide deliberations, covering nonmaleficence, beneficence, health equity, stewardship, and solidarity.”

It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9-14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. “When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind,” they say.

To achieve the goal of eliminating cervical cancer, “countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care,” they write. “Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals.”

Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9-14 years, as well as using additional resources to close the gap in these other areas.

Dr. Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. Dr. D’Souza and Dr. Nderitu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Billionaire entrepreneur Mark Cuban, owner of the NBA’s Dallas Mavericks, has launched a company offering generic medication at prices that are substantially lower than the current market listings, including several drugs used in oncology.

One of the drugs offering the biggest savings is generic imatinib (originator product Gleevec), which is used for chronic myelogenous leukemia (CML), certain acute lymphocytic leukemia (ALL) and certain types of gastrointestinal stromal tumors (GIST).

Imatinib has a list retail price of $2,502.

At the Mark Cuban pharmacy, it is available for $14.40, which offers a saving of $2,488.

The online pharmacy, known as the Mark Cuban Cost Plus Drug Company (MCCPDC), began operating in January. It is selling more than 100 generic prescription drugs at the cost of ingredients and manufacturing plus 15% margin, $3 pharmacy dispensing fee, and $5 shipping fee.

“We will do whatever it takes to get affordable pharmaceuticals to patients,” said Alex Oshmyansky, MD, PhD, founder and CEO of MCCPDC, in a company statement. “The markup on potentially lifesaving drugs that people depend on is a problem that can’t be ignored. It is imperative that we take action and help expand access to these medications for those who need them most.”

The company is a registered pharmaceutical wholesaler, and as such, can “bypass middlemen and outrageous markups,” the company notes in a press release. They have partnered with the digital health care company Truepill, which built and powers the pharmacy’s website.

At its launch, the pharmacy offered 109 generic medications. So far, the generics offered for oncology include generic anastrozole, letrozole, raloxifene, and tamoxifen for use in breast cancer, as well as the chemotherapy methotrexate and generic imatinib, as mentioned above.  All of the drugs sold through the MCCPDC have prices much lower than in the standard marketplace. Becker’s Hospital Review recently published a list of the 50 drugs with the biggest savings at Cuban’s pharmacy.

At the top of the list was albendazole, an anthelmintic that retails for $6,565. In contrast, the MCCPDC price is $453, which translates to a savings of more than $6,000 for a 30-count supply.

The second-largest savings was for imatinib.  

For the other cancer drugs, the savings were less substantial, reflecting their much lower retail price, but savings still ranged between $66 and $200 per product.

Overall, 14 of the top 50 discounted drugs are slated to save consumers more than $500 for a 30-count supply when purchased from MCCPDC.
 

Medicare could save billions

Medicare would save billions if it used this online pharmacy, say researchers from Harvard University, who recently published a study in Annals of Internal Medicine giving some estimates.

The team analyzed 89 generic drugs listed at MCCPDC and found that Medicare Part D could have saved more than $3 billion in 2020 if they had purchased them at these prices. For example, aripiprazole, a commonly used psychiatric medication, was purchased for more than $2 per pill, while the same generic formulation of the drug is sold by Cuban’s company for $0.24 per pill. Overall, just with this one drug, Medicare could have saved $233 million in 2020.

“We found that Medicare spent $9.6 billion on 89 generic drugs in 2020,” commented lead author Hussain S. Lalani, MD, MPH in a tweet. “It could have saved up to $3.6 billion on 77 of the 89 drugs if it purchased them at the largest quantity sold by Mark Cuban’s Cost Plus Drug Company. The other 12 drugs ($1.5B) did not offer savings.”

Dr. Lalani pointed out that the price transparency provided by MCCPDC is “helping us to understand the cost of many generic drugs and highlights inefficiencies in the supply chain for generic drugs.”

In standard practice, there are “multiple actors” involved in distributing the drug from the pharmaceutical manufacturer to the patient, he explained. “Mark Cuban’s company does not accept health insurance, buys from the manufacturer, and sells it directly to consumers online!”

He added that innovation and policy reform are needed. “We know that many drug prices are outrageous, and the supply chain is also expensive & NOT working right,” he tweeted. “We need a system that delivers innovative, affordable, and accessible medicines for all Americans.”

Commenting on Dr. Lalani’s Twitter thread, Eric Topol, MD, Medscape’s editor-in-chief, said that “the many billions the U.S. could save each year by MCCPDC is remarkable.”

Dr. Topol also noted that the savings estimated in the Annals of Internal Medicine paper were based on fewer than 100 generic drugs that are currently available, but he said that “there will be >1,000 more offered in the next year.”
 

No insurance, no PBMs

Prior to launching the online pharmacy, Mr. Cuban established a pharmacy benefit manager (PBM) operation to serve companies providing prescription coverage in their employee benefit plans. According to a press release, MCCPDC has pledged to be “radically transparent” in its own negotiations as a PBM, revealing the true costs it pays for drugs and eliminating spread pricing and misaligned rebate incentives. MCCPDC anticipates that its PBM could save companies millions of dollars with no changes to its benefits, as it will eliminate the traditional PBM model.

However, the online pharmacy is a cash-only venture, because MCCPDC refuses to pay third-party PBMs in order to be allowed to process insurance claims. But the model allows patients to immediately purchase medications at a cost that is often less than what they might pay when having to deal with deductible and copay requirements.

In the future, MCCPDC plans to start manufacturing medications. The company is currently building a state-of-the-art pharmaceutical facility in Dallas, at which it plans to produce its own high-quality medicines at the lowest possible prices.

A version of this article first appeared on Medscape.com.

Billionaire entrepreneur Mark Cuban, owner of the NBA’s Dallas Mavericks, has launched a company offering generic medication at prices that are substantially lower than the current market listings, including several drugs used in oncology.

One of the drugs offering the biggest savings is generic imatinib (originator product Gleevec), which is used for chronic myelogenous leukemia (CML), certain acute lymphocytic leukemia (ALL) and certain types of gastrointestinal stromal tumors (GIST).

Imatinib has a list retail price of $2,502.

At the Mark Cuban pharmacy, it is available for $14.40, which offers a saving of $2,488.

The online pharmacy, known as the Mark Cuban Cost Plus Drug Company (MCCPDC), began operating in January. It is selling more than 100 generic prescription drugs at the cost of ingredients and manufacturing plus 15% margin, $3 pharmacy dispensing fee, and $5 shipping fee.

“We will do whatever it takes to get affordable pharmaceuticals to patients,” said Alex Oshmyansky, MD, PhD, founder and CEO of MCCPDC, in a company statement. “The markup on potentially lifesaving drugs that people depend on is a problem that can’t be ignored. It is imperative that we take action and help expand access to these medications for those who need them most.”

The company is a registered pharmaceutical wholesaler, and as such, can “bypass middlemen and outrageous markups,” the company notes in a press release. They have partnered with the digital health care company Truepill, which built and powers the pharmacy’s website.

At its launch, the pharmacy offered 109 generic medications. So far, the generics offered for oncology include generic anastrozole, letrozole, raloxifene, and tamoxifen for use in breast cancer, as well as the chemotherapy methotrexate and generic imatinib, as mentioned above.  All of the drugs sold through the MCCPDC have prices much lower than in the standard marketplace. Becker’s Hospital Review recently published a list of the 50 drugs with the biggest savings at Cuban’s pharmacy.

At the top of the list was albendazole, an anthelmintic that retails for $6,565. In contrast, the MCCPDC price is $453, which translates to a savings of more than $6,000 for a 30-count supply.

The second-largest savings was for imatinib.  

For the other cancer drugs, the savings were less substantial, reflecting their much lower retail price, but savings still ranged between $66 and $200 per product.

Overall, 14 of the top 50 discounted drugs are slated to save consumers more than $500 for a 30-count supply when purchased from MCCPDC.
 

Medicare could save billions

Medicare would save billions if it used this online pharmacy, say researchers from Harvard University, who recently published a study in Annals of Internal Medicine giving some estimates.

The team analyzed 89 generic drugs listed at MCCPDC and found that Medicare Part D could have saved more than $3 billion in 2020 if they had purchased them at these prices. For example, aripiprazole, a commonly used psychiatric medication, was purchased for more than $2 per pill, while the same generic formulation of the drug is sold by Cuban’s company for $0.24 per pill. Overall, just with this one drug, Medicare could have saved $233 million in 2020.

“We found that Medicare spent $9.6 billion on 89 generic drugs in 2020,” commented lead author Hussain S. Lalani, MD, MPH in a tweet. “It could have saved up to $3.6 billion on 77 of the 89 drugs if it purchased them at the largest quantity sold by Mark Cuban’s Cost Plus Drug Company. The other 12 drugs ($1.5B) did not offer savings.”

Dr. Lalani pointed out that the price transparency provided by MCCPDC is “helping us to understand the cost of many generic drugs and highlights inefficiencies in the supply chain for generic drugs.”

In standard practice, there are “multiple actors” involved in distributing the drug from the pharmaceutical manufacturer to the patient, he explained. “Mark Cuban’s company does not accept health insurance, buys from the manufacturer, and sells it directly to consumers online!”

He added that innovation and policy reform are needed. “We know that many drug prices are outrageous, and the supply chain is also expensive & NOT working right,” he tweeted. “We need a system that delivers innovative, affordable, and accessible medicines for all Americans.”

Commenting on Dr. Lalani’s Twitter thread, Eric Topol, MD, Medscape’s editor-in-chief, said that “the many billions the U.S. could save each year by MCCPDC is remarkable.”

Dr. Topol also noted that the savings estimated in the Annals of Internal Medicine paper were based on fewer than 100 generic drugs that are currently available, but he said that “there will be >1,000 more offered in the next year.”
 

No insurance, no PBMs

Prior to launching the online pharmacy, Mr. Cuban established a pharmacy benefit manager (PBM) operation to serve companies providing prescription coverage in their employee benefit plans. According to a press release, MCCPDC has pledged to be “radically transparent” in its own negotiations as a PBM, revealing the true costs it pays for drugs and eliminating spread pricing and misaligned rebate incentives. MCCPDC anticipates that its PBM could save companies millions of dollars with no changes to its benefits, as it will eliminate the traditional PBM model.

However, the online pharmacy is a cash-only venture, because MCCPDC refuses to pay third-party PBMs in order to be allowed to process insurance claims. But the model allows patients to immediately purchase medications at a cost that is often less than what they might pay when having to deal with deductible and copay requirements.

In the future, MCCPDC plans to start manufacturing medications. The company is currently building a state-of-the-art pharmaceutical facility in Dallas, at which it plans to produce its own high-quality medicines at the lowest possible prices.

A version of this article first appeared on Medscape.com.

Billionaire entrepreneur Mark Cuban, owner of the NBA’s Dallas Mavericks, has launched a company offering generic medication at prices that are substantially lower than the current market listings, including several drugs used in oncology.

One of the drugs offering the biggest savings is generic imatinib (originator product Gleevec), which is used for chronic myelogenous leukemia (CML), certain acute lymphocytic leukemia (ALL) and certain types of gastrointestinal stromal tumors (GIST).

Imatinib has a list retail price of $2,502.

At the Mark Cuban pharmacy, it is available for $14.40, which offers a saving of $2,488.

The online pharmacy, known as the Mark Cuban Cost Plus Drug Company (MCCPDC), began operating in January. It is selling more than 100 generic prescription drugs at the cost of ingredients and manufacturing plus 15% margin, $3 pharmacy dispensing fee, and $5 shipping fee.

“We will do whatever it takes to get affordable pharmaceuticals to patients,” said Alex Oshmyansky, MD, PhD, founder and CEO of MCCPDC, in a company statement. “The markup on potentially lifesaving drugs that people depend on is a problem that can’t be ignored. It is imperative that we take action and help expand access to these medications for those who need them most.”

The company is a registered pharmaceutical wholesaler, and as such, can “bypass middlemen and outrageous markups,” the company notes in a press release. They have partnered with the digital health care company Truepill, which built and powers the pharmacy’s website.

At its launch, the pharmacy offered 109 generic medications. So far, the generics offered for oncology include generic anastrozole, letrozole, raloxifene, and tamoxifen for use in breast cancer, as well as the chemotherapy methotrexate and generic imatinib, as mentioned above.  All of the drugs sold through the MCCPDC have prices much lower than in the standard marketplace. Becker’s Hospital Review recently published a list of the 50 drugs with the biggest savings at Cuban’s pharmacy.

At the top of the list was albendazole, an anthelmintic that retails for $6,565. In contrast, the MCCPDC price is $453, which translates to a savings of more than $6,000 for a 30-count supply.

The second-largest savings was for imatinib.  

For the other cancer drugs, the savings were less substantial, reflecting their much lower retail price, but savings still ranged between $66 and $200 per product.

Overall, 14 of the top 50 discounted drugs are slated to save consumers more than $500 for a 30-count supply when purchased from MCCPDC.
 

Medicare could save billions

Medicare would save billions if it used this online pharmacy, say researchers from Harvard University, who recently published a study in Annals of Internal Medicine giving some estimates.

The team analyzed 89 generic drugs listed at MCCPDC and found that Medicare Part D could have saved more than $3 billion in 2020 if they had purchased them at these prices. For example, aripiprazole, a commonly used psychiatric medication, was purchased for more than $2 per pill, while the same generic formulation of the drug is sold by Cuban’s company for $0.24 per pill. Overall, just with this one drug, Medicare could have saved $233 million in 2020.

“We found that Medicare spent $9.6 billion on 89 generic drugs in 2020,” commented lead author Hussain S. Lalani, MD, MPH in a tweet. “It could have saved up to $3.6 billion on 77 of the 89 drugs if it purchased them at the largest quantity sold by Mark Cuban’s Cost Plus Drug Company. The other 12 drugs ($1.5B) did not offer savings.”

Dr. Lalani pointed out that the price transparency provided by MCCPDC is “helping us to understand the cost of many generic drugs and highlights inefficiencies in the supply chain for generic drugs.”

In standard practice, there are “multiple actors” involved in distributing the drug from the pharmaceutical manufacturer to the patient, he explained. “Mark Cuban’s company does not accept health insurance, buys from the manufacturer, and sells it directly to consumers online!”

He added that innovation and policy reform are needed. “We know that many drug prices are outrageous, and the supply chain is also expensive & NOT working right,” he tweeted. “We need a system that delivers innovative, affordable, and accessible medicines for all Americans.”

Commenting on Dr. Lalani’s Twitter thread, Eric Topol, MD, Medscape’s editor-in-chief, said that “the many billions the U.S. could save each year by MCCPDC is remarkable.”

Dr. Topol also noted that the savings estimated in the Annals of Internal Medicine paper were based on fewer than 100 generic drugs that are currently available, but he said that “there will be >1,000 more offered in the next year.”
 

No insurance, no PBMs

Prior to launching the online pharmacy, Mr. Cuban established a pharmacy benefit manager (PBM) operation to serve companies providing prescription coverage in their employee benefit plans. According to a press release, MCCPDC has pledged to be “radically transparent” in its own negotiations as a PBM, revealing the true costs it pays for drugs and eliminating spread pricing and misaligned rebate incentives. MCCPDC anticipates that its PBM could save companies millions of dollars with no changes to its benefits, as it will eliminate the traditional PBM model.

However, the online pharmacy is a cash-only venture, because MCCPDC refuses to pay third-party PBMs in order to be allowed to process insurance claims. But the model allows patients to immediately purchase medications at a cost that is often less than what they might pay when having to deal with deductible and copay requirements.

In the future, MCCPDC plans to start manufacturing medications. The company is currently building a state-of-the-art pharmaceutical facility in Dallas, at which it plans to produce its own high-quality medicines at the lowest possible prices.

A version of this article first appeared on Medscape.com.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

A version of this article first appeared on Medscape.com.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

A version of this article first appeared on Medscape.com.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

A version of this article first appeared on Medscape.com.