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Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.

But a new analysis of breast cancer deaths supports a “race and ethnicity-adapted” approach to breast screening, with Black women starting screening 8 years sooner – at age 42.

The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.

The study was published online in JAMA Network Open.

Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.

Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.

“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”

The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.

Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.

The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.

For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).

If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.

If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.

If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.

Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.

“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.

Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.

“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”

The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
 

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

The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.

But a new analysis of breast cancer deaths supports a “race and ethnicity-adapted” approach to breast screening, with Black women starting screening 8 years sooner – at age 42.

The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.

The study was published online in JAMA Network Open.

Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.

Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.

“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”

The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.

Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.

The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.

For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).

If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.

If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.

If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.

Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.

“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.

Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.

“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”

The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
 

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

The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.

But a new analysis of breast cancer deaths supports a “race and ethnicity-adapted” approach to breast screening, with Black women starting screening 8 years sooner – at age 42.

The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.

The study was published online in JAMA Network Open.

Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.

Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.

“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”

The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.

Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.

The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.

For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).

If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.

If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.

If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.

Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.

“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.

Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.

“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”

The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
 

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

A deep learning artificial intelligence (AI) model that used only a single histopathological slide predicted the risk of distant recurrence among endometrial cancer patients in a new study.

Endometrial cancer is the most frequently occurring uterine cancer. Early-stage patients have about a 95% 5-year survival, but distant recurrence is associated with very poor survival, according to Sarah Fremond, MSc, an author of the research (Abstract 5695), which she presented at the annual meeting of the American Association for Cancer Research.

“Most patients with endometrial cancer have a good prognosis and would not require any adjuvant treatment, but there is a proportion that will develop distant recurrence. For those you want to recommend adjuvant chemotherapy, because currently in the adjuvant setting, that’s the only treatment that is known to lower the risk of distant recurrence. But that also causes morbidity. Therefore, our clinical question was how to accurately identify patients at low and high risk of distant recurrence to reduce under- and overtreatment,” said Ms. Fremond, a PhD candidate at Leiden (the Netherlands) University Medical Center.

Pathologists can attempt such predictions, but Ms. Fremond noted that there are challenges. “There is a lot of variability between pathologists, and we don’t even use the entire visual information present in the H&E [hematoxylin and eosin] tumor slide. When it comes to molecular testing, it is hampered by cost, turnaround time, and sometimes interpretation. It’s quite complex to combine those data to specifically target risk of distant recurrence for patients with endometrial cancer.”

In her presentation, Ms. Fremond described how she and her colleagues used digitized histopathological slides in their research. She and her coauthors developed the AI model as part of a collaboration that included the AIRMEC Consortium, Leiden University Medical Center, the TransPORTEC Consortium, and the University of Zürich.

The researchers used long-term follow-up data from 1,408 patients drawn from three clinical cohorts and participants in the PORTEC-1, PORTEC-2, and PORTEC-3 studies, which tested radiotherapy and adjuvant therapy outcomes in endometrial cancer. Patients who had received prior adjuvant chemotherapy were excluded. In the model development phase, the system analyzed a single representative histopathological slide image from each patient and compared it with the known time to distant recurrence to identify patterns.

Once the system had been trained, the researchers applied it to a novel group of 353 patients. It ranked 89 patients as having a low risk of recurrence, 175 at intermediate risk, and 89 at high risk of recurrence. The system performed well: 3.37% of low-risk patients experienced a distant recurrence, as did 15.43% of the intermediate-risk group and 36% of the high-risk group.

The researchers also employed an external validation group with 152 patients and three slides per patient, with a 2.8-year follow-up. The model performed with a C index of 0.805 (±0.0136) when a random slide was selected for each patient, and the median predicted risk score per patient was associated with differences in distant recurrence-free survival between the three risk groups with a C index of 0.816 (P < .0001).
 

Questions about research and their answers

Session moderator Kristin Swanson, PhD, asked if the AI could be used with the pathology slide’s visible features to learn more about the underlying biology and pathophysiology of tumors.

“Overlying the HECTOR on to the tissue seems like a logical opportunity to go and then explore the biology and what’s attributed as a high-risk region,” said Dr. Swanson, who is director of the Mathematical NeuroOncology Lab and codirector of the Precision NeuroTherapeutics Innovation Program at Mayo Clinic Arizona, Phoenix.

Ms. Fremond agreed that the AI has the potential to be used that way.”

During the Q&A, an audience member asked how likely the model is to perform in populations that differ significantly from the populations used in her study.

Ms. Fremond responded that the populations used to develop and test the models were in or close to the Netherlands, and little information was available regarding patient ethnicity. “There is a possibility that perhaps we would have a different performance on a population that includes more minorities. That needs to be checked,” said Ms. Fremond.

The study is limited by its retrospective nature.

Ms. Fremond and Dr. Swanson have no relevant financial disclosures.

A deep learning artificial intelligence (AI) model that used only a single histopathological slide predicted the risk of distant recurrence among endometrial cancer patients in a new study.

Endometrial cancer is the most frequently occurring uterine cancer. Early-stage patients have about a 95% 5-year survival, but distant recurrence is associated with very poor survival, according to Sarah Fremond, MSc, an author of the research (Abstract 5695), which she presented at the annual meeting of the American Association for Cancer Research.

“Most patients with endometrial cancer have a good prognosis and would not require any adjuvant treatment, but there is a proportion that will develop distant recurrence. For those you want to recommend adjuvant chemotherapy, because currently in the adjuvant setting, that’s the only treatment that is known to lower the risk of distant recurrence. But that also causes morbidity. Therefore, our clinical question was how to accurately identify patients at low and high risk of distant recurrence to reduce under- and overtreatment,” said Ms. Fremond, a PhD candidate at Leiden (the Netherlands) University Medical Center.

Pathologists can attempt such predictions, but Ms. Fremond noted that there are challenges. “There is a lot of variability between pathologists, and we don’t even use the entire visual information present in the H&E [hematoxylin and eosin] tumor slide. When it comes to molecular testing, it is hampered by cost, turnaround time, and sometimes interpretation. It’s quite complex to combine those data to specifically target risk of distant recurrence for patients with endometrial cancer.”

In her presentation, Ms. Fremond described how she and her colleagues used digitized histopathological slides in their research. She and her coauthors developed the AI model as part of a collaboration that included the AIRMEC Consortium, Leiden University Medical Center, the TransPORTEC Consortium, and the University of Zürich.

The researchers used long-term follow-up data from 1,408 patients drawn from three clinical cohorts and participants in the PORTEC-1, PORTEC-2, and PORTEC-3 studies, which tested radiotherapy and adjuvant therapy outcomes in endometrial cancer. Patients who had received prior adjuvant chemotherapy were excluded. In the model development phase, the system analyzed a single representative histopathological slide image from each patient and compared it with the known time to distant recurrence to identify patterns.

Once the system had been trained, the researchers applied it to a novel group of 353 patients. It ranked 89 patients as having a low risk of recurrence, 175 at intermediate risk, and 89 at high risk of recurrence. The system performed well: 3.37% of low-risk patients experienced a distant recurrence, as did 15.43% of the intermediate-risk group and 36% of the high-risk group.

The researchers also employed an external validation group with 152 patients and three slides per patient, with a 2.8-year follow-up. The model performed with a C index of 0.805 (±0.0136) when a random slide was selected for each patient, and the median predicted risk score per patient was associated with differences in distant recurrence-free survival between the three risk groups with a C index of 0.816 (P < .0001).
 

Questions about research and their answers

Session moderator Kristin Swanson, PhD, asked if the AI could be used with the pathology slide’s visible features to learn more about the underlying biology and pathophysiology of tumors.

“Overlying the HECTOR on to the tissue seems like a logical opportunity to go and then explore the biology and what’s attributed as a high-risk region,” said Dr. Swanson, who is director of the Mathematical NeuroOncology Lab and codirector of the Precision NeuroTherapeutics Innovation Program at Mayo Clinic Arizona, Phoenix.

Ms. Fremond agreed that the AI has the potential to be used that way.”

During the Q&A, an audience member asked how likely the model is to perform in populations that differ significantly from the populations used in her study.

Ms. Fremond responded that the populations used to develop and test the models were in or close to the Netherlands, and little information was available regarding patient ethnicity. “There is a possibility that perhaps we would have a different performance on a population that includes more minorities. That needs to be checked,” said Ms. Fremond.

The study is limited by its retrospective nature.

Ms. Fremond and Dr. Swanson have no relevant financial disclosures.

A deep learning artificial intelligence (AI) model that used only a single histopathological slide predicted the risk of distant recurrence among endometrial cancer patients in a new study.

Endometrial cancer is the most frequently occurring uterine cancer. Early-stage patients have about a 95% 5-year survival, but distant recurrence is associated with very poor survival, according to Sarah Fremond, MSc, an author of the research (Abstract 5695), which she presented at the annual meeting of the American Association for Cancer Research.

“Most patients with endometrial cancer have a good prognosis and would not require any adjuvant treatment, but there is a proportion that will develop distant recurrence. For those you want to recommend adjuvant chemotherapy, because currently in the adjuvant setting, that’s the only treatment that is known to lower the risk of distant recurrence. But that also causes morbidity. Therefore, our clinical question was how to accurately identify patients at low and high risk of distant recurrence to reduce under- and overtreatment,” said Ms. Fremond, a PhD candidate at Leiden (the Netherlands) University Medical Center.

Pathologists can attempt such predictions, but Ms. Fremond noted that there are challenges. “There is a lot of variability between pathologists, and we don’t even use the entire visual information present in the H&E [hematoxylin and eosin] tumor slide. When it comes to molecular testing, it is hampered by cost, turnaround time, and sometimes interpretation. It’s quite complex to combine those data to specifically target risk of distant recurrence for patients with endometrial cancer.”

In her presentation, Ms. Fremond described how she and her colleagues used digitized histopathological slides in their research. She and her coauthors developed the AI model as part of a collaboration that included the AIRMEC Consortium, Leiden University Medical Center, the TransPORTEC Consortium, and the University of Zürich.

The researchers used long-term follow-up data from 1,408 patients drawn from three clinical cohorts and participants in the PORTEC-1, PORTEC-2, and PORTEC-3 studies, which tested radiotherapy and adjuvant therapy outcomes in endometrial cancer. Patients who had received prior adjuvant chemotherapy were excluded. In the model development phase, the system analyzed a single representative histopathological slide image from each patient and compared it with the known time to distant recurrence to identify patterns.

Once the system had been trained, the researchers applied it to a novel group of 353 patients. It ranked 89 patients as having a low risk of recurrence, 175 at intermediate risk, and 89 at high risk of recurrence. The system performed well: 3.37% of low-risk patients experienced a distant recurrence, as did 15.43% of the intermediate-risk group and 36% of the high-risk group.

The researchers also employed an external validation group with 152 patients and three slides per patient, with a 2.8-year follow-up. The model performed with a C index of 0.805 (±0.0136) when a random slide was selected for each patient, and the median predicted risk score per patient was associated with differences in distant recurrence-free survival between the three risk groups with a C index of 0.816 (P < .0001).
 

Questions about research and their answers

Session moderator Kristin Swanson, PhD, asked if the AI could be used with the pathology slide’s visible features to learn more about the underlying biology and pathophysiology of tumors.

“Overlying the HECTOR on to the tissue seems like a logical opportunity to go and then explore the biology and what’s attributed as a high-risk region,” said Dr. Swanson, who is director of the Mathematical NeuroOncology Lab and codirector of the Precision NeuroTherapeutics Innovation Program at Mayo Clinic Arizona, Phoenix.

Ms. Fremond agreed that the AI has the potential to be used that way.”

During the Q&A, an audience member asked how likely the model is to perform in populations that differ significantly from the populations used in her study.

Ms. Fremond responded that the populations used to develop and test the models were in or close to the Netherlands, and little information was available regarding patient ethnicity. “There is a possibility that perhaps we would have a different performance on a population that includes more minorities. That needs to be checked,” said Ms. Fremond.

The study is limited by its retrospective nature.

Ms. Fremond and Dr. Swanson have no relevant financial disclosures.

Tarek Mouhieddine, MD, grew up as a child of war-torn Lebanon. Now building his career as a New York–based hematologist oncologist, Dr. Mouhieddine works in the trenches of a very different kind of battle. His mission: Find a way to reverse multiple myeloma in its mysterious early “smoldering” stages and give patients a new lease on life before the cancer takes hold.

“If we start treatment earlier, in the smoldering phase, maybe there is a chance of actually curing the disease and completely getting rid of it,” said Dr. Mouhieddine, 31, a research fellow at the Icahn School of Medicine at Mount Sinai, in New York. “We haven’t proven that yet, and it’s going to take years before we’re able to prove it. I’m hoping to be one of those spearheading the initiative.”

Dr. Tarek Mouhieddine

As he develops clinical trials, the young physician scientist has another focus: A deeply personal connection to the very disease he’s trying to cure. Last year Dr. Mouhieddine diagnosed his aunt back in Lebanon with multiple myeloma. “I have always been close to her, and I’m like her son,” he said, and her situation is especially scary because she lives in a country where treatment options are limited.

Dr. Mouhieddine was born and raised in Beirut, the son of a sports journalist father and a mother who worked in a bank. Lebanon’s civil war ended in 1990, shortly before his birth, but political instability returned when he was a child.

“Everything was a disaster,” he recalled. “There was a period of time when there were bombs throughout the city because certain politicians were being targeted. I remember when groups of people would have gunfights in the street.”

Dr. Mouhieddine attended the American University of Beirut, then after college and medical school there, he headed to the United States.

“I wanted to make a difference in medicine. And I knew that if I stayed back home, I wouldn’t be able to,” he said. Fortunately, “everybody has made me feel that I really belong here, and I’ve never felt like I’m an outsider.”

Early on, as he went through fellowships and residency, he developed an interest in multiple myeloma.

Ajai Chari, MD, a colleague of Dr. Mouhieddine’s at Icahn School of Medicine, said in an interview, “I remember meeting him at a conference before he had even started an internal medicine residency, let alone a hematology oncology fellowship. He was already certain he wanted to work in multiple myeloma, due to his work at Dana-Farber Cancer Institute.”

Myeloma was especially intriguing to Dr. Mouhieddine because of the rapid rate of progress in treating the disease. “Over the past 10 years, the myeloma field has advanced at such an extremely fast pace, more than any other cancer,” he said. “Maybe 15 years ago, you would tell someone with newly diagnosed myeloma that they had a chance for an average of another 2 years. Now, we tell patients they have 10 years to live on average, which means you could live 15 or 20 years. That alone was astounding to me and piqued my interest in myeloma.”

At the same time, smoldering myeloma – which can be discovered during routine blood work – remains little understood. As the National Cancer Institute explains, “smoldering myeloma is a precancerous condition that alters certain proteins in blood and/or increases plasma cells in bone marrow, but it does not cause symptoms of disease. About half of those diagnosed with the condition, however, will develop multiple myeloma within 5 years.”

“If we understand what drives smoldering myeloma, we may be able to prevent it from progressing to its active form,” said hematologist oncologist Samir Parekh, MD, who works with Dr. Mouhieddine at Icahn School of Medicine. “Or at the minimum, we could better predict who will progress so we can tailor therapy for high-risk patients and minimize toxicity by not overtreating patients who may not need therapy.”

Dr. Mouhieddine’s current work is focusing on developing clinical trials to test whether immunotherapy can snuff out myeloma when it’s at the smoldering stage, “before anything bad happens.

“If a myeloma patient comes in with renal failure, and we treat the myeloma at that stage, it doesn’t mean that the patient’s kidneys are gonna go back to normal. A lot of the damage can be permanent,” he said. “Even when you treat multiple myeloma, and it goes into remission, it ends up coming back. And you just have to go from one therapy to the other.”

In contrast, a successful treatment for smoldering myeloma would prevent progression to the full disease. In other words, it would be a cure – which is now elusive.

Specifically, Dr. Mouhieddine hopes to test whether bispecific antibodies, a type of immunotherapy that enlists the body’s T cells to kill myeloma cells, will be effective in the smoldering phase. Bispecific antibodies are now being explored as treatments for full multiple myeloma when the immune system is weaker, he said, and they may be even more effective earlier, when the body is better equipped to fight off the disease.

Dr. Mouhieddine hopes better treatments for multiple myeloma itself will help save his 64-year-old aunt Hassana, back in Beirut. He diagnosed her in 2022 after she told him that she felt tired all the time and underwent various tests. The woman he calls his “second mom” is doing well, despite struggles to buy medication due to the lack of access to bank funds in Lebanon.

Dr. Tarek Mouhieddine

Tarek Mouhieddine, MD, grew up as a child of war-torn Lebanon. Now building his career as a New York–based hematologist oncologist, Dr. Mouhieddine works in the trenches of a very different kind of battle. His mission: Find a way to reverse multiple myeloma in its mysterious early “smoldering” stages and give patients a new lease on life before the cancer takes hold.

“If we start treatment earlier, in the smoldering phase, maybe there is a chance of actually curing the disease and completely getting rid of it,” said Dr. Mouhieddine, 31, a research fellow at the Icahn School of Medicine at Mount Sinai, in New York. “We haven’t proven that yet, and it’s going to take years before we’re able to prove it. I’m hoping to be one of those spearheading the initiative.”

Dr. Tarek Mouhieddine

As he develops clinical trials, the young physician scientist has another focus: A deeply personal connection to the very disease he’s trying to cure. Last year Dr. Mouhieddine diagnosed his aunt back in Lebanon with multiple myeloma. “I have always been close to her, and I’m like her son,” he said, and her situation is especially scary because she lives in a country where treatment options are limited.

Dr. Mouhieddine was born and raised in Beirut, the son of a sports journalist father and a mother who worked in a bank. Lebanon’s civil war ended in 1990, shortly before his birth, but political instability returned when he was a child.

“Everything was a disaster,” he recalled. “There was a period of time when there were bombs throughout the city because certain politicians were being targeted. I remember when groups of people would have gunfights in the street.”

Dr. Mouhieddine attended the American University of Beirut, then after college and medical school there, he headed to the United States.

“I wanted to make a difference in medicine. And I knew that if I stayed back home, I wouldn’t be able to,” he said. Fortunately, “everybody has made me feel that I really belong here, and I’ve never felt like I’m an outsider.”

Early on, as he went through fellowships and residency, he developed an interest in multiple myeloma.

Ajai Chari, MD, a colleague of Dr. Mouhieddine’s at Icahn School of Medicine, said in an interview, “I remember meeting him at a conference before he had even started an internal medicine residency, let alone a hematology oncology fellowship. He was already certain he wanted to work in multiple myeloma, due to his work at Dana-Farber Cancer Institute.”

Myeloma was especially intriguing to Dr. Mouhieddine because of the rapid rate of progress in treating the disease. “Over the past 10 years, the myeloma field has advanced at such an extremely fast pace, more than any other cancer,” he said. “Maybe 15 years ago, you would tell someone with newly diagnosed myeloma that they had a chance for an average of another 2 years. Now, we tell patients they have 10 years to live on average, which means you could live 15 or 20 years. That alone was astounding to me and piqued my interest in myeloma.”

At the same time, smoldering myeloma – which can be discovered during routine blood work – remains little understood. As the National Cancer Institute explains, “smoldering myeloma is a precancerous condition that alters certain proteins in blood and/or increases plasma cells in bone marrow, but it does not cause symptoms of disease. About half of those diagnosed with the condition, however, will develop multiple myeloma within 5 years.”

“If we understand what drives smoldering myeloma, we may be able to prevent it from progressing to its active form,” said hematologist oncologist Samir Parekh, MD, who works with Dr. Mouhieddine at Icahn School of Medicine. “Or at the minimum, we could better predict who will progress so we can tailor therapy for high-risk patients and minimize toxicity by not overtreating patients who may not need therapy.”

Dr. Mouhieddine’s current work is focusing on developing clinical trials to test whether immunotherapy can snuff out myeloma when it’s at the smoldering stage, “before anything bad happens.

“If a myeloma patient comes in with renal failure, and we treat the myeloma at that stage, it doesn’t mean that the patient’s kidneys are gonna go back to normal. A lot of the damage can be permanent,” he said. “Even when you treat multiple myeloma, and it goes into remission, it ends up coming back. And you just have to go from one therapy to the other.”

In contrast, a successful treatment for smoldering myeloma would prevent progression to the full disease. In other words, it would be a cure – which is now elusive.

Specifically, Dr. Mouhieddine hopes to test whether bispecific antibodies, a type of immunotherapy that enlists the body’s T cells to kill myeloma cells, will be effective in the smoldering phase. Bispecific antibodies are now being explored as treatments for full multiple myeloma when the immune system is weaker, he said, and they may be even more effective earlier, when the body is better equipped to fight off the disease.

Dr. Mouhieddine hopes better treatments for multiple myeloma itself will help save his 64-year-old aunt Hassana, back in Beirut. He diagnosed her in 2022 after she told him that she felt tired all the time and underwent various tests. The woman he calls his “second mom” is doing well, despite struggles to buy medication due to the lack of access to bank funds in Lebanon.

Dr. Tarek Mouhieddine

Tarek Mouhieddine, MD, grew up as a child of war-torn Lebanon. Now building his career as a New York–based hematologist oncologist, Dr. Mouhieddine works in the trenches of a very different kind of battle. His mission: Find a way to reverse multiple myeloma in its mysterious early “smoldering” stages and give patients a new lease on life before the cancer takes hold.

“If we start treatment earlier, in the smoldering phase, maybe there is a chance of actually curing the disease and completely getting rid of it,” said Dr. Mouhieddine, 31, a research fellow at the Icahn School of Medicine at Mount Sinai, in New York. “We haven’t proven that yet, and it’s going to take years before we’re able to prove it. I’m hoping to be one of those spearheading the initiative.”

Dr. Tarek Mouhieddine

As he develops clinical trials, the young physician scientist has another focus: A deeply personal connection to the very disease he’s trying to cure. Last year Dr. Mouhieddine diagnosed his aunt back in Lebanon with multiple myeloma. “I have always been close to her, and I’m like her son,” he said, and her situation is especially scary because she lives in a country where treatment options are limited.

Dr. Mouhieddine was born and raised in Beirut, the son of a sports journalist father and a mother who worked in a bank. Lebanon’s civil war ended in 1990, shortly before his birth, but political instability returned when he was a child.

“Everything was a disaster,” he recalled. “There was a period of time when there were bombs throughout the city because certain politicians were being targeted. I remember when groups of people would have gunfights in the street.”

Dr. Mouhieddine attended the American University of Beirut, then after college and medical school there, he headed to the United States.

“I wanted to make a difference in medicine. And I knew that if I stayed back home, I wouldn’t be able to,” he said. Fortunately, “everybody has made me feel that I really belong here, and I’ve never felt like I’m an outsider.”

Early on, as he went through fellowships and residency, he developed an interest in multiple myeloma.

Ajai Chari, MD, a colleague of Dr. Mouhieddine’s at Icahn School of Medicine, said in an interview, “I remember meeting him at a conference before he had even started an internal medicine residency, let alone a hematology oncology fellowship. He was already certain he wanted to work in multiple myeloma, due to his work at Dana-Farber Cancer Institute.”

Myeloma was especially intriguing to Dr. Mouhieddine because of the rapid rate of progress in treating the disease. “Over the past 10 years, the myeloma field has advanced at such an extremely fast pace, more than any other cancer,” he said. “Maybe 15 years ago, you would tell someone with newly diagnosed myeloma that they had a chance for an average of another 2 years. Now, we tell patients they have 10 years to live on average, which means you could live 15 or 20 years. That alone was astounding to me and piqued my interest in myeloma.”

At the same time, smoldering myeloma – which can be discovered during routine blood work – remains little understood. As the National Cancer Institute explains, “smoldering myeloma is a precancerous condition that alters certain proteins in blood and/or increases plasma cells in bone marrow, but it does not cause symptoms of disease. About half of those diagnosed with the condition, however, will develop multiple myeloma within 5 years.”

“If we understand what drives smoldering myeloma, we may be able to prevent it from progressing to its active form,” said hematologist oncologist Samir Parekh, MD, who works with Dr. Mouhieddine at Icahn School of Medicine. “Or at the minimum, we could better predict who will progress so we can tailor therapy for high-risk patients and minimize toxicity by not overtreating patients who may not need therapy.”

Dr. Mouhieddine’s current work is focusing on developing clinical trials to test whether immunotherapy can snuff out myeloma when it’s at the smoldering stage, “before anything bad happens.

“If a myeloma patient comes in with renal failure, and we treat the myeloma at that stage, it doesn’t mean that the patient’s kidneys are gonna go back to normal. A lot of the damage can be permanent,” he said. “Even when you treat multiple myeloma, and it goes into remission, it ends up coming back. And you just have to go from one therapy to the other.”

In contrast, a successful treatment for smoldering myeloma would prevent progression to the full disease. In other words, it would be a cure – which is now elusive.

Specifically, Dr. Mouhieddine hopes to test whether bispecific antibodies, a type of immunotherapy that enlists the body’s T cells to kill myeloma cells, will be effective in the smoldering phase. Bispecific antibodies are now being explored as treatments for full multiple myeloma when the immune system is weaker, he said, and they may be even more effective earlier, when the body is better equipped to fight off the disease.

Dr. Mouhieddine hopes better treatments for multiple myeloma itself will help save his 64-year-old aunt Hassana, back in Beirut. He diagnosed her in 2022 after she told him that she felt tired all the time and underwent various tests. The woman he calls his “second mom” is doing well, despite struggles to buy medication due to the lack of access to bank funds in Lebanon.

Dr. Tarek Mouhieddine

Combination treatment with the poly ADP-ribose polymerase inhibitor, olaparib, and the novel ataxia telangiectasia–mutated Rad3-related (ATR) inhibitor, ceralasertib, was well tolerated and showed some promise in pediatric patients with tumors with DNA replication stress or DNA repair deficiencies, in a new study.

The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.

The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.

In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.

In adults, poly ADP-ribose polymerase (PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.

Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.

The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.

Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.

There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.

An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.

Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.

“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.

She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.

“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.

The study is limited by its small sample size and the fact that it was not randomized.

The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.

Combination treatment with the poly ADP-ribose polymerase inhibitor, olaparib, and the novel ataxia telangiectasia–mutated Rad3-related (ATR) inhibitor, ceralasertib, was well tolerated and showed some promise in pediatric patients with tumors with DNA replication stress or DNA repair deficiencies, in a new study.

The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.

The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.

In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.

In adults, poly ADP-ribose polymerase (PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.

Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.

The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.

Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.

There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.

An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.

Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.

“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.

She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.

“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.

The study is limited by its small sample size and the fact that it was not randomized.

The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.

Combination treatment with the poly ADP-ribose polymerase inhibitor, olaparib, and the novel ataxia telangiectasia–mutated Rad3-related (ATR) inhibitor, ceralasertib, was well tolerated and showed some promise in pediatric patients with tumors with DNA replication stress or DNA repair deficiencies, in a new study.

The small phase 1 trial also identified some molecular signatures in responders that may inform future clinical trials.

The results, presented at the annual meeting of the American Association of Cancer Research, came from a single arm of the European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) trial. This trial matches pediatric, adolescent, and young adult cancer patients with treatment regimens based on the molecular profile of their tumors.

In over 220 children to date, the trial has investigated 15 different treatment regimens, most of which are combination therapies.

In adults, poly ADP-ribose polymerase (PARP) inhibitors have been shown to be effective in tumors with deficiencies in homologous repair, which is a DNA repair mechanism, with notable successes in patients carrying the BRCA1 and BRCA2 mutations. But BRCA1 and BRCA2 mutations are rare in pediatric cancer, and there is a belief that there may be primary resistance to PARP inhibitors in pediatric tumors, according to Susanne Gatz, MD, PhD, who presented the research at the meeting.

Previous research identified alterations in pediatric tumors that are candidates for patient selection. “These tumors have alterations which could potentially cause this resistance effect [against PARP inhibitors] and [also cause] sensitivity to ataxia telangiectasia–mutated Rad3-related inhibitors. This is how this arm [of the ESMART trial] was born,” said Dr. Gatz.

The phase 1 portion of the study included 18 pediatric and young adult patients with relapsed or treatment-refractory tumors. There were eight sarcomas, five central nervous system tumors, four neuroblastomas, and one carcinoma. Each had mutations thought to lead to HR deficiency or replication stress. The study included three dose levels of twice-daily oral olaparib that was given continuously, and ceralasertib, which was given day 1-14 of each 28-day cycle.

Patients underwent a median of 3.5 cycles of treatment. There were dose-limiting adverse events of thrombocytopenia and neutropenia in five patients, two of which occurred at the dose that was recommended for phase 2.

There were some positive clinical signs, including one partial response in a pineoblastoma patient who received treatment for 11 cycles. A neuroblastoma patient had stable disease until cycle 9 of treatment, and then converted to a partial response and is currently in cycle 12. Two other patients remain in treatment at cycle 8 and one is in treatment at cycle 15. None of the patients who experienced clinical benefit had BRCA mutations.

An important goal of the study was to understand molecular signature that might predict response to the drug combination. Although no firm conclusions could be drawn, there were some interesting patterns. In particular, five of the six worst responders had TP53 mutations. “It is striking ... so we need to learn what TP53 in this setting means if it’s mutated, and if it could be a resistance factor,” said Dr. Gatz, an associate clinical professor in pediatric oncology at the Institute of Cancer and Genomic Sciences of the University of Birmingham, during her talk.

Although the study is too small and included too many tumor types to identify tumor-based patterns of response, it did provide some hints as to biomarkers that could inform future studies, according to Julia Glade Bender, MD, who served as a discussant following the presentation and is a pediatric oncologist at Memorial Sloan Kettering Cancer Center, New York.

“The pediatric frequency of the common DNA damage repair biomarkers that have been [identified in] the adult literature – that is to say, BRCA1 and 2 and [ataxia-telangiectasia mutation] – are exceedingly rare in pediatrics,” said Dr. Bender during the session while serving as a discussant. She highlighted the following findings: Loss of the 11q region on chromosome 11 is common among the patients and that region contains three genes involved in the DNA damage response, along with a gene involved in homologous recombination, telomere maintenance, and double strand break repair.

She added that 11q deletion is also found in up to 40% of neuroblastomas, and is associated with poor prognosis, and the patients have multiple segmental chromosomal abnormalities. “That begs the question [of] whether chromosomal instability is another biomarker for pediatric cancer,” said Dr. Bender.

“The research highlights the complexity of pediatric cancers, whose distinct biology could make them more vulnerable to ATR [kinase], [checkpoint kinase 1], and WEE1 pathway inhibition with a PARP inhibitor used to induce replication stress and be the sensitizer. The biomarker profiles are going to be complex, context-dependent, and likely to reflect a constellation of findings that would be signatures or algorithms, rather than single gene alterations. The post hoc iterative analysis of responders and nonresponders is going to be absolutely critical to understanding those biomarkers and the role of DNA damage response inhibitors in pediatrics. Given the rarity of these diagnoses, and then the molecular subclasses, I think collaboration across ages and geography is absolutely critical, and I really congratulate the ESMART consortium for doing just that in Europe,” said Dr. Bender.

The study is limited by its small sample size and the fact that it was not randomized.

The study received funding from French Institut National de Cancer, Imagine for Margo, Fondation ARC, AstraZeneca France, AstraZeneca Global R&D, AstraZeneca UK, Cancer Research UK, Fondation Gustave Roussy, and Little Princess Trust/Children’s Cancer and Leukaemia Group. Dr. Gatz has no relevant financial disclosures. Dr. Bender has done paid consulting for Jazz Pharmaceuticals and has done unpaid work for Bristol-Myers Squibb, Eisai, Springworks Therapeutics, Merck Sharp & Dohme, and Pfizer. She has received research support from Eli Lilly, Loxo-oncology, Eisai, Cellectar, Bayer, Amgen, and Jazz Pharmaceuticals.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Abstract CT019. Presented Tuesday, April 18.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

Cancer screening remains challenging. There are screens available for a handful of solid tumors, but uptake is low caused in part by health care access barriers as well as the potential for unnecessary follow-up procedures, according to Phillip Febbo, MD.

These issues could threaten efforts like that of President Joe Biden’s Cancer Moonshot initiative, which aims to reduce cancer mortality by 50%. Advances in circulating tumor (ct) DNA analysis could help address these problems, but a lack of diversity among study participants needs to be addressed to ensure it has broad utility, continued Dr. Febbo, during his presentation at the annual meeting of the American Association for Cancer Research.

The problem is particularly acute among African American, Hispanic, and other underserved populations who often face health care barriers that can exacerbate the issue, said Dr. Febbo, who is chief medical officer for Illumina. The lack of access is compounded by the fact that there are only currently screens for lung, breast, colorectal, cervical, and prostate cancer, leaving a vast unmet need.

“We still do not have screening tests for 70% of the deaths that are due to cancer,” he said.

ctDNA released from dying cancer cells has the potential to reveal a wide range of cancer types and reduce barriers to access, because it is based on a blood test. It can be analyzed for various factors, including mutations, chromosomal rearrangements, methylation patterns, and other characteristics that hint at the presence of cancer. However, it can’t be successful without sufficient inclusion in research studies, Dr. Febbo explained.

“We have to ensure we have the right representation [of] populations when we develop these tests, when we go through the clinical trials, and as we bring these into communities,” he said.

During his presentation, Dr. Febbo shared a slide showing that about 78% of participants in published gene-association studies were White.

ctDNA showed promise in at least on recent study. Dr. Febbo discussed the ECLIPSE trial, which used the Guardant Health SHIELD assay for colorectal cancer (CRC). About 13% of its approximately 20,000 participants were Black or African American, 15% were Hispanic, and 7% were Asian Americans. It also included both urban and rural individuals. In results announced in December 2022, the researchers found a sensitivity of 83%, which was lower than the 92.3% found in standard CRC screening, but above the 74% threshold set by the Food and Drug Administration. The specificity was 90%.

One approach that could dramatically change the landscape of cancer screening is a multicancer early detection (MCED) test, according to Dr. Febbo. The CancerSeek MCED test, developed by Johns Hopkins Kimmel Cancer Center researchers, uses a series of genetic and protein biomarkers to detect all cancers, with the exception of leukemia, skin cancer, and central nervous system tumors. Among 10,006 women aged between 65 and 75 years with no history of cancer, it had a sensitivity of 27.1% and a specificity of 98.9%, with a positive predictive value of 19.4%. The study’s population was 95% non-Hispanic White.

He also discussed the Pathfinder study, sponsored by the Illumina subsidiary Grail, which included 6,662 individuals age 50 and over from seven sites in the United States, and grouped them into normal and increased risk; 92% were non-Hispanic White. It used the Galleri MCED test, which performed with a sensitivity of 29%, specificity of 99.1%, and a positive predictive value of 38.0%. False positives produced to limited burden, with 93% undergoing imaging, 28% nonsurgical invasive procedures, and 2% undergoing fruitless invasive surgical procedures.

Dr. Febbo touted the potential for such tests to greatly reduce cancer mortality, but only if there is adequate uptake of screening procedures, particularly in underserved groups. He put up a slide of a model showing that MCED has the potential to reduce cancer mortality by 20%, but only if the screen is widely accepted among all groups. “I’ve had my team model this. If we accept the current use of screening tests, and we don’t address disparities, and we don’t ensure everybody feels included and participates actively – not only in the research, but also in the testing and adoption, you would cut that potential benefit in half. That would be hundreds of thousands of lives lost because we didn’t address disparities.”
 

Successful recruiting of African Americans for research

Following Dr. Febbo’s talk, Karriem Watson, MS, spoke about some potential solutions to the issue, including his own experiences and success stories in recruiting African Americans to play active roles in research. He is chief engagement officer for the National Institute of Health’s All of Us Research Program, which aims to gather health data on at least 1 million residents of the United States. Mr. Watson has spent time reaching out to people living in communities in the Chicago area to encourage participation in breast cancer screening. An event at his church inspired his own sister to get a mammogram, and she was diagnosed with early-stage breast cancer.

“I’m a living witness that early engagement can lead to early detection,” said Mr. Watson during his talk.

He reported that the All of Us research program has succeeded in creating diversity within its data collection, as 46.7% of participants identify as racial and ethnic minorities.

Mr. Watson took issue with the common perception that underrepresented communities may be hard to reach.

“I want to challenge us to think outside the box and really ask ourselves: Are populations hard to reach, or are there opportunities for us to do better and more intentional engagement?” He went on to describe a program to recruit African American men as citizen scientists. He and his colleagues developed a network that included barbers, faith leaders, and fraternity and civic organization members to help recruit participants for a prostate cancer screening project. They exceeded their initial recruitment goal.

They went on to develop a network of barbers in the south and west sides of Chicago to recruit individuals to participate in studies of protein methylation and lung cancer screening, as well as a project that investigated associations between neighborhood of residence and lung cancer. The results of those efforts have also informed other projects, including a smoking cessation study. “We’ve not only included African American men in our research, but we’ve included them as part of our research team,” said Mr. Watson.

Dr. Febbo is also a stockholder of Illumina. Mr. Watson has no relevant financial disclosures.

From American Association for Cancer Research (AACR) Annual Meeting 2023: Improving cancer outcomes through equitable access to cfDNA tests. Presented Monday, April 17, 2023.

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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

The Food and Drug Administration approved omidubicel-onlv (Omisirge) for reducing infections and hastening neutrophil recovery for blood cancer patients aged 12 years and older who are undergoing allogeneic umbilical cord blood stem cell transplants.

Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B₃, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.

The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.

The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.

The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.

The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.

Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”

The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.

Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.

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