Hematology Times

The first international public survey on cancer perceptions and attitudes in a decade shows that, in spite of progress, low socioeconomic status and lack of education continue to jeopardize the health of the world’s most vulnerable populations.

The survey was commissioned by the Union for International Cancer Control (UICC) to mark the 20th anniversary of World Cancer Day on Feb. 4, 2020.

The survey, which was conducted by Ipsos, was taken by more than 15,000 people in 20 countries. It shows that people of lower socioeconomic status are less likely than those in higher-income households to recognize the risk factors for cancer or to make lifestyle changes. With the exception of tobacco use, people with low educational attainment also showed less cancer awareness and were less likely to engage in preventive behaviors than those with a university degree.

It is “unacceptable that millions of people have a greater chance of developing cancer in their lifetime because they are simply not aware of the cancer risks to avoid and the healthy behaviors to adopt – information that many of us take for granted. And this is true around the world,” Cary Adams, MBA, CEO of the UICC, commented in a statement.

The survey was conducted from Oct. 25 to Nov., 2019, and included 15,427 participants from Australia, Bolivia, Brazil, Canada, China, France, Germany, Great Britain, India, Israel, Japan, Kenya, Mexico, the Philippines, Saudi Arabia, South Africa, Spain, Sweden, Turkey, and the United States.

The vast majority of those surveyed – 87% – said they were aware of the major risk factors for cancer, while only 6% said they were not.

The cancer risk factors that were most recognized were tobacco use (63%), ultraviolet light exposure (54%), and exposure to secondhand tobacco smoke (50%).

The cancer risks that were least recognized included being overweight (29%), a lack of exercise (28%), and exposure to certain viruses or bacteria (28%).

The difference in awareness across the social spectrum was striking. “Emerging from the survey are the apparent and glaring inequities faced by socioeconomically disadvantaged groups,” the authors said.

“Much more must be done to ensure that everyone has an equal chance to reduce their risk of preventable cancer,” commented Sonali Johnson, PhD, head of knowledge, advocacy, and policy at the UICC in Geneva, Switzerland.

“We’ve seen in the results that those surveyed with a lower education and those on lower incomes appear less aware of the main risk factors associated with cancer and thus are less likely to proactively take the steps needed to reduce their cancer risk as compared to those from a high income household or those with a university education,” Dr. Johnson said in an interview.

Does increased cancer awareness translate into behavioral change for the better? This question can only be answered by more research, the survey authors said. They reported that 7 of 10 survey respondents (69%) said they had made a behavioral change to reduce their cancer risk within the past 12 months. Most said they were eating more healthfully.

Slightly fewer than one-quarter reported that they had not taken any preventive measures in the past year.

When it comes to raising cancer awareness, World Cancer Day is “a powerful tool to remind every person that they can play a crucial role in reducing the impact of cancer,” said Dr. Johnson.
 

Health care providers are “crucial”

Reacting to the findings of the survey, the European Society for Medical Oncology (ESMO) emphasized the key role that physicians play in cancer prevention.

“Research speaks very clearly for prevention,” said ESMO President Solange Peters, MD, PhD. “With the number of cancer cases expected to rise to 29.5 million by 2040, we must act now. ESMO is committed to educating doctors on all aspects of cancer control, which should begin well before a cancer diagnosis.

“In the face of this emergency, which is rendered even more salient by the results of the report, we must work to enlarge the basis of doctors who are properly educated and trained in key prevention measures,” Dr. Peters added. “General practitioners and organ specialists are in the front line to guide and support patients on their quest for healthy lifestyles and reliable ways to detect cancer early.”

In a comment, Dr. Johnson acknowledged the role physicians play in health promotion and informing patients about noncommunicable disease risks, including those related to cancer. However, she emphasized that nurses, pharmacists, community health workers, midwives, and other health care providers who deliver primary care “are crucial around the world to imparting health information and offering services.”

Frontline health care workers can assess patients’ cancer knowledge and health literacy, determine the barriers to health care, and assess “how best to engage with people across the life course,” Dr. Johnson explained. “Rather than just focusing on physicians, we must work with all those involved in primary care, especially as primary care services are scaled up to achieve universal health coverage.”

Call on governments to do more

The authors noted that, although there is wide awareness of the cancer risks from tobacco use, adults younger than 35 years were less likely than those older than 50 to identify tobacco as a cancer risk factor. They described this finding as “most concerning” and said it “underscores the ongoing need to raise awareness about cancer risk factors in every new generation.”

Almost 60% of survey respondents, regardless of age, education, or income, expressed concern about being diagnosed with cancer in the future or having cancer recur.

In Kenya, where the death toll from cancer rose 30% from 2014 to 2018, people appeared to be the most worried about cancer, with four of five survey respondents (82%) expressing concern.

Survey respondents from Saudi Arabia appeared the least concerned, with one of three people saying they were worried.

Notably, 84% of survey respondents said that governments should be doing more to increase cancer prevention and awareness; 33% demanded that governments improve the affordability of cancer care.

“It is understandable that people turn to their governments for support,” Dr. Johnson commented. “Affordability is a big challenge for low-income settings.”

Data from the World Health Organization show that, for every U.S. $1 invested in low- and middle-income countries, the return is U.S. $3.20, Johnson pointed out. “We really need to convince decision makers ... and see the right investments being made. It is important to ensure that the health system strengthening takes place in tandem with prevention services.”

Governments have begun making commitments to tackle noncommunicable diseases and cancer, Dr. Johnson commented. He highlighted the WHO’s Global Action Plan for Healthy Lives and Well-being for All and the updated cancer resolution adopted at the 2017 World Health Assembly.

“Education, training, and awareness-raising efforts need to be backed by strong and progressive health policies that prioritize prevention and help reduce the consumption of known cancer-causing products such as tobacco, sugary food, and beverages,” she said. “Countries should also invest proactively in national cancer control planning and the establishment of population-based registries to ensure the most effective resource allocation that benefits all groups.”

Up-to-date information on cancer risks and cancer prevention must be delivered to the public in ways that are accessible to those in lower socioeconomic groups, Dr. Johnson added. “Awareness needs to be raised continuously with each new generation,” she noted.

The UICC has relationships with Astellas, Daiichi Sankyo, Diaceutics, MSD Inventing for Life, Bristol-Myers Squibb, CUBEBIO, the Icon Group, Roche, and Sanofi.

This article first appeared on Medscape.com.

The first international public survey on cancer perceptions and attitudes in a decade shows that, in spite of progress, low socioeconomic status and lack of education continue to jeopardize the health of the world’s most vulnerable populations.

The survey was commissioned by the Union for International Cancer Control (UICC) to mark the 20th anniversary of World Cancer Day on Feb. 4, 2020.

The survey, which was conducted by Ipsos, was taken by more than 15,000 people in 20 countries. It shows that people of lower socioeconomic status are less likely than those in higher-income households to recognize the risk factors for cancer or to make lifestyle changes. With the exception of tobacco use, people with low educational attainment also showed less cancer awareness and were less likely to engage in preventive behaviors than those with a university degree.

It is “unacceptable that millions of people have a greater chance of developing cancer in their lifetime because they are simply not aware of the cancer risks to avoid and the healthy behaviors to adopt – information that many of us take for granted. And this is true around the world,” Cary Adams, MBA, CEO of the UICC, commented in a statement.

The survey was conducted from Oct. 25 to Nov., 2019, and included 15,427 participants from Australia, Bolivia, Brazil, Canada, China, France, Germany, Great Britain, India, Israel, Japan, Kenya, Mexico, the Philippines, Saudi Arabia, South Africa, Spain, Sweden, Turkey, and the United States.

The vast majority of those surveyed – 87% – said they were aware of the major risk factors for cancer, while only 6% said they were not.

The cancer risk factors that were most recognized were tobacco use (63%), ultraviolet light exposure (54%), and exposure to secondhand tobacco smoke (50%).

The cancer risks that were least recognized included being overweight (29%), a lack of exercise (28%), and exposure to certain viruses or bacteria (28%).

The difference in awareness across the social spectrum was striking. “Emerging from the survey are the apparent and glaring inequities faced by socioeconomically disadvantaged groups,” the authors said.

“Much more must be done to ensure that everyone has an equal chance to reduce their risk of preventable cancer,” commented Sonali Johnson, PhD, head of knowledge, advocacy, and policy at the UICC in Geneva, Switzerland.

“We’ve seen in the results that those surveyed with a lower education and those on lower incomes appear less aware of the main risk factors associated with cancer and thus are less likely to proactively take the steps needed to reduce their cancer risk as compared to those from a high income household or those with a university education,” Dr. Johnson said in an interview.

Does increased cancer awareness translate into behavioral change for the better? This question can only be answered by more research, the survey authors said. They reported that 7 of 10 survey respondents (69%) said they had made a behavioral change to reduce their cancer risk within the past 12 months. Most said they were eating more healthfully.

Slightly fewer than one-quarter reported that they had not taken any preventive measures in the past year.

When it comes to raising cancer awareness, World Cancer Day is “a powerful tool to remind every person that they can play a crucial role in reducing the impact of cancer,” said Dr. Johnson.
 

Health care providers are “crucial”

Reacting to the findings of the survey, the European Society for Medical Oncology (ESMO) emphasized the key role that physicians play in cancer prevention.

“Research speaks very clearly for prevention,” said ESMO President Solange Peters, MD, PhD. “With the number of cancer cases expected to rise to 29.5 million by 2040, we must act now. ESMO is committed to educating doctors on all aspects of cancer control, which should begin well before a cancer diagnosis.

“In the face of this emergency, which is rendered even more salient by the results of the report, we must work to enlarge the basis of doctors who are properly educated and trained in key prevention measures,” Dr. Peters added. “General practitioners and organ specialists are in the front line to guide and support patients on their quest for healthy lifestyles and reliable ways to detect cancer early.”

In a comment, Dr. Johnson acknowledged the role physicians play in health promotion and informing patients about noncommunicable disease risks, including those related to cancer. However, she emphasized that nurses, pharmacists, community health workers, midwives, and other health care providers who deliver primary care “are crucial around the world to imparting health information and offering services.”

Frontline health care workers can assess patients’ cancer knowledge and health literacy, determine the barriers to health care, and assess “how best to engage with people across the life course,” Dr. Johnson explained. “Rather than just focusing on physicians, we must work with all those involved in primary care, especially as primary care services are scaled up to achieve universal health coverage.”

Call on governments to do more

The authors noted that, although there is wide awareness of the cancer risks from tobacco use, adults younger than 35 years were less likely than those older than 50 to identify tobacco as a cancer risk factor. They described this finding as “most concerning” and said it “underscores the ongoing need to raise awareness about cancer risk factors in every new generation.”

Almost 60% of survey respondents, regardless of age, education, or income, expressed concern about being diagnosed with cancer in the future or having cancer recur.

In Kenya, where the death toll from cancer rose 30% from 2014 to 2018, people appeared to be the most worried about cancer, with four of five survey respondents (82%) expressing concern.

Survey respondents from Saudi Arabia appeared the least concerned, with one of three people saying they were worried.

Notably, 84% of survey respondents said that governments should be doing more to increase cancer prevention and awareness; 33% demanded that governments improve the affordability of cancer care.

“It is understandable that people turn to their governments for support,” Dr. Johnson commented. “Affordability is a big challenge for low-income settings.”

Data from the World Health Organization show that, for every U.S. $1 invested in low- and middle-income countries, the return is U.S. $3.20, Johnson pointed out. “We really need to convince decision makers ... and see the right investments being made. It is important to ensure that the health system strengthening takes place in tandem with prevention services.”

Governments have begun making commitments to tackle noncommunicable diseases and cancer, Dr. Johnson commented. He highlighted the WHO’s Global Action Plan for Healthy Lives and Well-being for All and the updated cancer resolution adopted at the 2017 World Health Assembly.

“Education, training, and awareness-raising efforts need to be backed by strong and progressive health policies that prioritize prevention and help reduce the consumption of known cancer-causing products such as tobacco, sugary food, and beverages,” she said. “Countries should also invest proactively in national cancer control planning and the establishment of population-based registries to ensure the most effective resource allocation that benefits all groups.”

Up-to-date information on cancer risks and cancer prevention must be delivered to the public in ways that are accessible to those in lower socioeconomic groups, Dr. Johnson added. “Awareness needs to be raised continuously with each new generation,” she noted.

The UICC has relationships with Astellas, Daiichi Sankyo, Diaceutics, MSD Inventing for Life, Bristol-Myers Squibb, CUBEBIO, the Icon Group, Roche, and Sanofi.

This article first appeared on Medscape.com.

The first international public survey on cancer perceptions and attitudes in a decade shows that, in spite of progress, low socioeconomic status and lack of education continue to jeopardize the health of the world’s most vulnerable populations.

The survey was commissioned by the Union for International Cancer Control (UICC) to mark the 20th anniversary of World Cancer Day on Feb. 4, 2020.

The survey, which was conducted by Ipsos, was taken by more than 15,000 people in 20 countries. It shows that people of lower socioeconomic status are less likely than those in higher-income households to recognize the risk factors for cancer or to make lifestyle changes. With the exception of tobacco use, people with low educational attainment also showed less cancer awareness and were less likely to engage in preventive behaviors than those with a university degree.

It is “unacceptable that millions of people have a greater chance of developing cancer in their lifetime because they are simply not aware of the cancer risks to avoid and the healthy behaviors to adopt – information that many of us take for granted. And this is true around the world,” Cary Adams, MBA, CEO of the UICC, commented in a statement.

The survey was conducted from Oct. 25 to Nov., 2019, and included 15,427 participants from Australia, Bolivia, Brazil, Canada, China, France, Germany, Great Britain, India, Israel, Japan, Kenya, Mexico, the Philippines, Saudi Arabia, South Africa, Spain, Sweden, Turkey, and the United States.

The vast majority of those surveyed – 87% – said they were aware of the major risk factors for cancer, while only 6% said they were not.

The cancer risk factors that were most recognized were tobacco use (63%), ultraviolet light exposure (54%), and exposure to secondhand tobacco smoke (50%).

The cancer risks that were least recognized included being overweight (29%), a lack of exercise (28%), and exposure to certain viruses or bacteria (28%).

The difference in awareness across the social spectrum was striking. “Emerging from the survey are the apparent and glaring inequities faced by socioeconomically disadvantaged groups,” the authors said.

“Much more must be done to ensure that everyone has an equal chance to reduce their risk of preventable cancer,” commented Sonali Johnson, PhD, head of knowledge, advocacy, and policy at the UICC in Geneva, Switzerland.

“We’ve seen in the results that those surveyed with a lower education and those on lower incomes appear less aware of the main risk factors associated with cancer and thus are less likely to proactively take the steps needed to reduce their cancer risk as compared to those from a high income household or those with a university education,” Dr. Johnson said in an interview.

Does increased cancer awareness translate into behavioral change for the better? This question can only be answered by more research, the survey authors said. They reported that 7 of 10 survey respondents (69%) said they had made a behavioral change to reduce their cancer risk within the past 12 months. Most said they were eating more healthfully.

Slightly fewer than one-quarter reported that they had not taken any preventive measures in the past year.

When it comes to raising cancer awareness, World Cancer Day is “a powerful tool to remind every person that they can play a crucial role in reducing the impact of cancer,” said Dr. Johnson.
 

Health care providers are “crucial”

Reacting to the findings of the survey, the European Society for Medical Oncology (ESMO) emphasized the key role that physicians play in cancer prevention.

“Research speaks very clearly for prevention,” said ESMO President Solange Peters, MD, PhD. “With the number of cancer cases expected to rise to 29.5 million by 2040, we must act now. ESMO is committed to educating doctors on all aspects of cancer control, which should begin well before a cancer diagnosis.

“In the face of this emergency, which is rendered even more salient by the results of the report, we must work to enlarge the basis of doctors who are properly educated and trained in key prevention measures,” Dr. Peters added. “General practitioners and organ specialists are in the front line to guide and support patients on their quest for healthy lifestyles and reliable ways to detect cancer early.”

In a comment, Dr. Johnson acknowledged the role physicians play in health promotion and informing patients about noncommunicable disease risks, including those related to cancer. However, she emphasized that nurses, pharmacists, community health workers, midwives, and other health care providers who deliver primary care “are crucial around the world to imparting health information and offering services.”

Frontline health care workers can assess patients’ cancer knowledge and health literacy, determine the barriers to health care, and assess “how best to engage with people across the life course,” Dr. Johnson explained. “Rather than just focusing on physicians, we must work with all those involved in primary care, especially as primary care services are scaled up to achieve universal health coverage.”

Call on governments to do more

The authors noted that, although there is wide awareness of the cancer risks from tobacco use, adults younger than 35 years were less likely than those older than 50 to identify tobacco as a cancer risk factor. They described this finding as “most concerning” and said it “underscores the ongoing need to raise awareness about cancer risk factors in every new generation.”

Almost 60% of survey respondents, regardless of age, education, or income, expressed concern about being diagnosed with cancer in the future or having cancer recur.

In Kenya, where the death toll from cancer rose 30% from 2014 to 2018, people appeared to be the most worried about cancer, with four of five survey respondents (82%) expressing concern.

Survey respondents from Saudi Arabia appeared the least concerned, with one of three people saying they were worried.

Notably, 84% of survey respondents said that governments should be doing more to increase cancer prevention and awareness; 33% demanded that governments improve the affordability of cancer care.

“It is understandable that people turn to their governments for support,” Dr. Johnson commented. “Affordability is a big challenge for low-income settings.”

Data from the World Health Organization show that, for every U.S. $1 invested in low- and middle-income countries, the return is U.S. $3.20, Johnson pointed out. “We really need to convince decision makers ... and see the right investments being made. It is important to ensure that the health system strengthening takes place in tandem with prevention services.”

Governments have begun making commitments to tackle noncommunicable diseases and cancer, Dr. Johnson commented. He highlighted the WHO’s Global Action Plan for Healthy Lives and Well-being for All and the updated cancer resolution adopted at the 2017 World Health Assembly.

“Education, training, and awareness-raising efforts need to be backed by strong and progressive health policies that prioritize prevention and help reduce the consumption of known cancer-causing products such as tobacco, sugary food, and beverages,” she said. “Countries should also invest proactively in national cancer control planning and the establishment of population-based registries to ensure the most effective resource allocation that benefits all groups.”

Up-to-date information on cancer risks and cancer prevention must be delivered to the public in ways that are accessible to those in lower socioeconomic groups, Dr. Johnson added. “Awareness needs to be raised continuously with each new generation,” she noted.

The UICC has relationships with Astellas, Daiichi Sankyo, Diaceutics, MSD Inventing for Life, Bristol-Myers Squibb, CUBEBIO, the Icon Group, Roche, and Sanofi.

This article first appeared on Medscape.com.

Newly discovered gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may improve understanding of clinical resistance mechanisms underlying the disease, according to recent research.

“We investigated patients with progressive CLL on venetoclax harboring subclonal BCL2 Gly101Val mutations for the presence of additional acquired BCL2 resistance mutations,” wrote Piers Blombery, MBBS, of the University of Melbourne in Victoria, Australia, and his colleagues in Blood.

Among 67 patients with relapsed disease treated with the BCL2 inhibitor venetoclax, the researchers identified a total of 11 patients with co-occurring BCL2 Gly101Val mutations. Each patient was enrolled in an early phase clinical trial at an institution in Australia.

With respect to testing methods, next-generation sequencing (NGS) and hybridization-based target enrichment technologies were used to detect novel acquired mutations in the BCL2 coding region.

Among those harboring the Gly101Val mutation, additional BCL2 mutations were identified in 10 patients (91%), with a median of three mutations detected per patient (range, 1-7). Previously undescribed mutations included an in-frame insertion mutation (Arg107_Arg110dup), and other substitutions (Asp103/Val156) in the BCL2 gene.

“As with the Gly101Val, these observations support the specificity of these mutations for the context of venetoclax resistance,” they wrote.

The investigators further explained that the BCL2 Asp103Glu mutation could have particular significance in the context of venetoclax sensitivity because of selective targeting of the BCL2 gene.

In comparison to wild-type aspartic acid, the BCL2 Asp103Glu substitution was linked to an approximate 20-fold reduction in affinity for venetoclax, they reported.

“[Our findings] consolidate the paradigm emerging across hematological malignancies of multiple independent molecular mechanisms underpinning an ‘oligoclonal’ pattern of clinical relapse on targeted therapies,” they concluded.

Further studies are needed to fully characterize the relationship between acquired BCL2 mutations and venetoclax resistance.

The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.

Newly discovered gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may improve understanding of clinical resistance mechanisms underlying the disease, according to recent research.

“We investigated patients with progressive CLL on venetoclax harboring subclonal BCL2 Gly101Val mutations for the presence of additional acquired BCL2 resistance mutations,” wrote Piers Blombery, MBBS, of the University of Melbourne in Victoria, Australia, and his colleagues in Blood.

Among 67 patients with relapsed disease treated with the BCL2 inhibitor venetoclax, the researchers identified a total of 11 patients with co-occurring BCL2 Gly101Val mutations. Each patient was enrolled in an early phase clinical trial at an institution in Australia.

With respect to testing methods, next-generation sequencing (NGS) and hybridization-based target enrichment technologies were used to detect novel acquired mutations in the BCL2 coding region.

Among those harboring the Gly101Val mutation, additional BCL2 mutations were identified in 10 patients (91%), with a median of three mutations detected per patient (range, 1-7). Previously undescribed mutations included an in-frame insertion mutation (Arg107_Arg110dup), and other substitutions (Asp103/Val156) in the BCL2 gene.

“As with the Gly101Val, these observations support the specificity of these mutations for the context of venetoclax resistance,” they wrote.

The investigators further explained that the BCL2 Asp103Glu mutation could have particular significance in the context of venetoclax sensitivity because of selective targeting of the BCL2 gene.

In comparison to wild-type aspartic acid, the BCL2 Asp103Glu substitution was linked to an approximate 20-fold reduction in affinity for venetoclax, they reported.

“[Our findings] consolidate the paradigm emerging across hematological malignancies of multiple independent molecular mechanisms underpinning an ‘oligoclonal’ pattern of clinical relapse on targeted therapies,” they concluded.

Further studies are needed to fully characterize the relationship between acquired BCL2 mutations and venetoclax resistance.

The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.

Newly discovered gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may improve understanding of clinical resistance mechanisms underlying the disease, according to recent research.

“We investigated patients with progressive CLL on venetoclax harboring subclonal BCL2 Gly101Val mutations for the presence of additional acquired BCL2 resistance mutations,” wrote Piers Blombery, MBBS, of the University of Melbourne in Victoria, Australia, and his colleagues in Blood.

Among 67 patients with relapsed disease treated with the BCL2 inhibitor venetoclax, the researchers identified a total of 11 patients with co-occurring BCL2 Gly101Val mutations. Each patient was enrolled in an early phase clinical trial at an institution in Australia.

With respect to testing methods, next-generation sequencing (NGS) and hybridization-based target enrichment technologies were used to detect novel acquired mutations in the BCL2 coding region.

Among those harboring the Gly101Val mutation, additional BCL2 mutations were identified in 10 patients (91%), with a median of three mutations detected per patient (range, 1-7). Previously undescribed mutations included an in-frame insertion mutation (Arg107_Arg110dup), and other substitutions (Asp103/Val156) in the BCL2 gene.

“As with the Gly101Val, these observations support the specificity of these mutations for the context of venetoclax resistance,” they wrote.

The investigators further explained that the BCL2 Asp103Glu mutation could have particular significance in the context of venetoclax sensitivity because of selective targeting of the BCL2 gene.

In comparison to wild-type aspartic acid, the BCL2 Asp103Glu substitution was linked to an approximate 20-fold reduction in affinity for venetoclax, they reported.

“[Our findings] consolidate the paradigm emerging across hematological malignancies of multiple independent molecular mechanisms underpinning an ‘oligoclonal’ pattern of clinical relapse on targeted therapies,” they concluded.

Further studies are needed to fully characterize the relationship between acquired BCL2 mutations and venetoclax resistance.

The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) provides “robust, sustained efficacy” in patients with Hodgkin lymphoma, according to investigators.

In the ECHELON-1 trial, investigators compared A+AVD to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for stage III or IV Hodgkin lymphoma. The 3-year progression-free survival (PFS) was superior in patients who received A+AVD, and this benefit was seen across most subgroups.

David J. Straus, MD, of Memorial Sloan Kettering Cancer Center in New York and his colleagues detailed these findings in Blood.

The phase 3 trial (NCT01712490) enrolled 1,334 patients with stage III or IV classical Hodgkin lymphoma. They were randomized to receive A+AVD (n = 664) or ABVD (n = 670). Baseline characteristics were similar between the treatment arms.

Positron emission tomography status after cycle 2 (PET2) was similar between the treatment arms as well. Most patients – 89% of the A+AVD arm and 86% of the ABVD arm – were PET2 negative. Treating physicians used PET2 status as a guide to potentially switch patients to an alternative regimen (radiotherapy or chemotherapy with or without transplant).

In a prior analysis, the study’s primary endpoint was modified PFS (time to progression, death, or noncomplete response after frontline therapy) per an independent review committee (N Engl J Med. 2018;378:331-44). The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm (hazard ratio, 0.77; P = .04).

PFS update

In the current analysis, the main exploratory endpoint was PFS per investigator. The 3-year PFS rate was significantly higher in the A+AVD arm than in the ABVD arm – 83.1% and 76.0%, respectively (HR, 0.704; P = .005).

The investigators observed a “consistent improvement in PFS” in the A+AVD arm, regardless of disease stage, International Prognostic score, Eastern Cooperative Oncology Group status, sex, or age. There was a significant improvement in PFS with A+AVD in PET2-negative patients and a trend toward improvement in PET2-positive patients. In the PET2-negative patients, the 3-year PFS was 85.8% in the A+AVD arm and 79.5% in the ABVD arm (HR, 0.69; P = .009). In PET2-positive patients, the 3-year PFS was 67.7% and 51.5%, respectively (HR, 0.59; P = .077).

“These data highlight that A+AVD provides a durable efficacy benefit, compared with ABVD, for frontline stage III/IV cHL [classical Hodgkin lymphoma], which is consistent across key subgroups regardless of patient status at PET2,” Dr. Straus and his colleagues wrote.

Safety update

In both treatment arms, peripheral neuropathy continued to improve or resolve with longer follow-up. Among patients who developed peripheral neuropathy, 78% in the A+AVD arm and 83% in the ABVD arm had improvement or resolution of the condition at 3 years.

Most patients had complete resolution of peripheral neuropathy; 62% in the A+AVD arm and 73% in the ABVD arm. The median time to complete resolution was 28 weeks (range, 0-167 weeks) after stopping A+AVD and 14 weeks (range, 0-188 weeks) after stopping ABVD.

The incidence of secondary malignancies was similar between the treatment arms. There were 14 secondary malignancies in the A+AVD arm (6 solid tumors, 8 hematologic malignancies) and 20 in the ABVD arm (9 solid tumors, 11 hematologic malignancies).

“A+AVD provided a sustained PFS benefit with a predictable and manageable safety profile,” Dr. Straus and colleagues wrote. “These data further support the advantages of A+AVD versus ABVD as frontline treatment of patients with advanced stage III or IV cHL [classical Hodgkin lymphoma].”

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals (a subsidiary of Takeda) and Seattle Genetics. The investigators disclosed relationships with Millennium, Takeda, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Straus DJ et al. Blood. 2020 Jan 16. pii: blood.2019003127. doi: 10.1182/blood.2019003127.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) provides “robust, sustained efficacy” in patients with Hodgkin lymphoma, according to investigators.

In the ECHELON-1 trial, investigators compared A+AVD to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for stage III or IV Hodgkin lymphoma. The 3-year progression-free survival (PFS) was superior in patients who received A+AVD, and this benefit was seen across most subgroups.

David J. Straus, MD, of Memorial Sloan Kettering Cancer Center in New York and his colleagues detailed these findings in Blood.

The phase 3 trial (NCT01712490) enrolled 1,334 patients with stage III or IV classical Hodgkin lymphoma. They were randomized to receive A+AVD (n = 664) or ABVD (n = 670). Baseline characteristics were similar between the treatment arms.

Positron emission tomography status after cycle 2 (PET2) was similar between the treatment arms as well. Most patients – 89% of the A+AVD arm and 86% of the ABVD arm – were PET2 negative. Treating physicians used PET2 status as a guide to potentially switch patients to an alternative regimen (radiotherapy or chemotherapy with or without transplant).

In a prior analysis, the study’s primary endpoint was modified PFS (time to progression, death, or noncomplete response after frontline therapy) per an independent review committee (N Engl J Med. 2018;378:331-44). The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm (hazard ratio, 0.77; P = .04).

PFS update

In the current analysis, the main exploratory endpoint was PFS per investigator. The 3-year PFS rate was significantly higher in the A+AVD arm than in the ABVD arm – 83.1% and 76.0%, respectively (HR, 0.704; P = .005).

The investigators observed a “consistent improvement in PFS” in the A+AVD arm, regardless of disease stage, International Prognostic score, Eastern Cooperative Oncology Group status, sex, or age. There was a significant improvement in PFS with A+AVD in PET2-negative patients and a trend toward improvement in PET2-positive patients. In the PET2-negative patients, the 3-year PFS was 85.8% in the A+AVD arm and 79.5% in the ABVD arm (HR, 0.69; P = .009). In PET2-positive patients, the 3-year PFS was 67.7% and 51.5%, respectively (HR, 0.59; P = .077).

“These data highlight that A+AVD provides a durable efficacy benefit, compared with ABVD, for frontline stage III/IV cHL [classical Hodgkin lymphoma], which is consistent across key subgroups regardless of patient status at PET2,” Dr. Straus and his colleagues wrote.

Safety update

In both treatment arms, peripheral neuropathy continued to improve or resolve with longer follow-up. Among patients who developed peripheral neuropathy, 78% in the A+AVD arm and 83% in the ABVD arm had improvement or resolution of the condition at 3 years.

Most patients had complete resolution of peripheral neuropathy; 62% in the A+AVD arm and 73% in the ABVD arm. The median time to complete resolution was 28 weeks (range, 0-167 weeks) after stopping A+AVD and 14 weeks (range, 0-188 weeks) after stopping ABVD.

The incidence of secondary malignancies was similar between the treatment arms. There were 14 secondary malignancies in the A+AVD arm (6 solid tumors, 8 hematologic malignancies) and 20 in the ABVD arm (9 solid tumors, 11 hematologic malignancies).

“A+AVD provided a sustained PFS benefit with a predictable and manageable safety profile,” Dr. Straus and colleagues wrote. “These data further support the advantages of A+AVD versus ABVD as frontline treatment of patients with advanced stage III or IV cHL [classical Hodgkin lymphoma].”

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals (a subsidiary of Takeda) and Seattle Genetics. The investigators disclosed relationships with Millennium, Takeda, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Straus DJ et al. Blood. 2020 Jan 16. pii: blood.2019003127. doi: 10.1182/blood.2019003127.

Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) provides “robust, sustained efficacy” in patients with Hodgkin lymphoma, according to investigators.

In the ECHELON-1 trial, investigators compared A+AVD to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for stage III or IV Hodgkin lymphoma. The 3-year progression-free survival (PFS) was superior in patients who received A+AVD, and this benefit was seen across most subgroups.

David J. Straus, MD, of Memorial Sloan Kettering Cancer Center in New York and his colleagues detailed these findings in Blood.

The phase 3 trial (NCT01712490) enrolled 1,334 patients with stage III or IV classical Hodgkin lymphoma. They were randomized to receive A+AVD (n = 664) or ABVD (n = 670). Baseline characteristics were similar between the treatment arms.

Positron emission tomography status after cycle 2 (PET2) was similar between the treatment arms as well. Most patients – 89% of the A+AVD arm and 86% of the ABVD arm – were PET2 negative. Treating physicians used PET2 status as a guide to potentially switch patients to an alternative regimen (radiotherapy or chemotherapy with or without transplant).

In a prior analysis, the study’s primary endpoint was modified PFS (time to progression, death, or noncomplete response after frontline therapy) per an independent review committee (N Engl J Med. 2018;378:331-44). The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm (hazard ratio, 0.77; P = .04).

PFS update

In the current analysis, the main exploratory endpoint was PFS per investigator. The 3-year PFS rate was significantly higher in the A+AVD arm than in the ABVD arm – 83.1% and 76.0%, respectively (HR, 0.704; P = .005).

The investigators observed a “consistent improvement in PFS” in the A+AVD arm, regardless of disease stage, International Prognostic score, Eastern Cooperative Oncology Group status, sex, or age. There was a significant improvement in PFS with A+AVD in PET2-negative patients and a trend toward improvement in PET2-positive patients. In the PET2-negative patients, the 3-year PFS was 85.8% in the A+AVD arm and 79.5% in the ABVD arm (HR, 0.69; P = .009). In PET2-positive patients, the 3-year PFS was 67.7% and 51.5%, respectively (HR, 0.59; P = .077).

“These data highlight that A+AVD provides a durable efficacy benefit, compared with ABVD, for frontline stage III/IV cHL [classical Hodgkin lymphoma], which is consistent across key subgroups regardless of patient status at PET2,” Dr. Straus and his colleagues wrote.

Safety update

In both treatment arms, peripheral neuropathy continued to improve or resolve with longer follow-up. Among patients who developed peripheral neuropathy, 78% in the A+AVD arm and 83% in the ABVD arm had improvement or resolution of the condition at 3 years.

Most patients had complete resolution of peripheral neuropathy; 62% in the A+AVD arm and 73% in the ABVD arm. The median time to complete resolution was 28 weeks (range, 0-167 weeks) after stopping A+AVD and 14 weeks (range, 0-188 weeks) after stopping ABVD.

The incidence of secondary malignancies was similar between the treatment arms. There were 14 secondary malignancies in the A+AVD arm (6 solid tumors, 8 hematologic malignancies) and 20 in the ABVD arm (9 solid tumors, 11 hematologic malignancies).

“A+AVD provided a sustained PFS benefit with a predictable and manageable safety profile,” Dr. Straus and colleagues wrote. “These data further support the advantages of A+AVD versus ABVD as frontline treatment of patients with advanced stage III or IV cHL [classical Hodgkin lymphoma].”

The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals (a subsidiary of Takeda) and Seattle Genetics. The investigators disclosed relationships with Millennium, Takeda, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Straus DJ et al. Blood. 2020 Jan 16. pii: blood.2019003127. doi: 10.1182/blood.2019003127.

Incorporating lymphopenia into the Follicular Lymphoma International Prognostic Index (FLIPI) can improve prognostication, according to researchers.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

The team added lymphopenia as a point in a revised FLIPI scoring system, called FLIPI-L, and found the new system could better predict overall survival (OS), progression-free survival, and histologic transformation in patients with follicular lymphoma.

George Yang, MD, of Moffitt Cancer Center in Tampa, Fla., and his colleagues described results with the FLIPI-L in a letter published in Blood Cancer Journal.

“Prior studies have demonstrated that lymphopenia was associated with worsened OS in [follicular lymphoma],” Dr. Yang and his colleagues wrote. “Therefore, we hypothesized that lymphopenia may be integrated with existing FLIPI to better stratify long-term survival outcomes and predict for transformation.”

The researchers tested this theory in 736 follicular lymphoma patients who were followed for a median of 72 months (range, 2-211 months). The 5-year OS in this cohort was 81.3%, the 10-year OS was 67.3%, and 18% of patients experienced transformation to high-grade lymphoma.

The researchers defined absolute lymphopenia as less than 1.0 × 10⁹ lymphocytes per liter. In multivariate analyses, lymphopenia was an independent predictor of OS (hazard ratio, 1.74; P less than .01) and transformation (odds ratio, 2.1; P less than .01).

To incorporate lymphopenia into the FLIPI, the researchers created a model in which 1 point was given for each of the standard FLIPI components (age, Ann Arbor stage, number of nodal areas, lactate dehydrogenase, and hemoglobin level), and one point was given for the presence of lymphopenia. Patients in the low-risk FLIPI-L category had 0-1 points, those in the intermediate-risk category had 2-3 points, and patients in the high-risk FLIPI-L category had 4-6 points.

Using the original FLIPI, the 5-year OS was 91% in the low-risk group (0-1), 82.7% in the intermediate-risk group (2), and 66% in the high-risk group (3-5). The 10-year OS was 80.4%, 66%, and 45.8%, respectively.

Using the FLIPI-L, the 5-year OS was 94.5% in the low-risk group (0-1), 89% in the intermediate-risk group (2-3), and 61% in the high-risk group (4-6). The 10-year OS was 83.9%, 68.5%, and 34.5%, respectively.

In a univariate Cox regression analysis of OS, each point increase in FLIPI-L score was associated with a significant increase in hazard ratio. For example, the hazard ratio was 3.4 for patients with a FLIPI-L score of 1 and 30.9 for those with a FLIPI-L score of 6 (P less than .02 for all FLIPI-L scores). Conversely, increases in hazard ratio were not significant with the original FLIPI (P greater than .05 for all FLIPI scores).

The FLIPI-L was prognostic for OS in different treatment groups. In patients who received rituximab alone, radiation alone, or rituximab plus chemotherapy, the scoring system differentiated low-, intermediate-, and high-risk groups (P less than .04). In patients under observation, the FLIPI-L distinguished low/intermediate-risk and high-risk groups (P less than .01).

For patients who progressed within 24 months, the FLIPI-L was more predictive of progression-free survival (P = .05) than was the original FLIPI (P = .11).

Increasing FLIPI-L was an independent predictor of transformation, both when assessed as a continuous variable (P less than .01) and stepwise for FLIPI-L 3-5 (P = .004-.01). The original FLIPI, on the other hand, was not an independent predictor of transformation.

“Our analysis of a lymphopenia cutoff as an addition to the original FLIPI is simple yet improves risk stratification to differentiate between prognostic groups and, importantly, to predict transformation,” Dr. Yang and his colleagues wrote.

The authors reported having no conflicts of interest.
 

[email protected]

SOURCE: Yang G et al. Blood Cancer J. 2020 Jan 2;9(12):104. doi: 10.1038/s41408-019-0269-6.

Incorporating lymphopenia into the Follicular Lymphoma International Prognostic Index (FLIPI) can improve prognostication, according to researchers.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

The team added lymphopenia as a point in a revised FLIPI scoring system, called FLIPI-L, and found the new system could better predict overall survival (OS), progression-free survival, and histologic transformation in patients with follicular lymphoma.

George Yang, MD, of Moffitt Cancer Center in Tampa, Fla., and his colleagues described results with the FLIPI-L in a letter published in Blood Cancer Journal.

“Prior studies have demonstrated that lymphopenia was associated with worsened OS in [follicular lymphoma],” Dr. Yang and his colleagues wrote. “Therefore, we hypothesized that lymphopenia may be integrated with existing FLIPI to better stratify long-term survival outcomes and predict for transformation.”

The researchers tested this theory in 736 follicular lymphoma patients who were followed for a median of 72 months (range, 2-211 months). The 5-year OS in this cohort was 81.3%, the 10-year OS was 67.3%, and 18% of patients experienced transformation to high-grade lymphoma.

The researchers defined absolute lymphopenia as less than 1.0 × 10⁹ lymphocytes per liter. In multivariate analyses, lymphopenia was an independent predictor of OS (hazard ratio, 1.74; P less than .01) and transformation (odds ratio, 2.1; P less than .01).

To incorporate lymphopenia into the FLIPI, the researchers created a model in which 1 point was given for each of the standard FLIPI components (age, Ann Arbor stage, number of nodal areas, lactate dehydrogenase, and hemoglobin level), and one point was given for the presence of lymphopenia. Patients in the low-risk FLIPI-L category had 0-1 points, those in the intermediate-risk category had 2-3 points, and patients in the high-risk FLIPI-L category had 4-6 points.

Using the original FLIPI, the 5-year OS was 91% in the low-risk group (0-1), 82.7% in the intermediate-risk group (2), and 66% in the high-risk group (3-5). The 10-year OS was 80.4%, 66%, and 45.8%, respectively.

Using the FLIPI-L, the 5-year OS was 94.5% in the low-risk group (0-1), 89% in the intermediate-risk group (2-3), and 61% in the high-risk group (4-6). The 10-year OS was 83.9%, 68.5%, and 34.5%, respectively.

In a univariate Cox regression analysis of OS, each point increase in FLIPI-L score was associated with a significant increase in hazard ratio. For example, the hazard ratio was 3.4 for patients with a FLIPI-L score of 1 and 30.9 for those with a FLIPI-L score of 6 (P less than .02 for all FLIPI-L scores). Conversely, increases in hazard ratio were not significant with the original FLIPI (P greater than .05 for all FLIPI scores).

The FLIPI-L was prognostic for OS in different treatment groups. In patients who received rituximab alone, radiation alone, or rituximab plus chemotherapy, the scoring system differentiated low-, intermediate-, and high-risk groups (P less than .04). In patients under observation, the FLIPI-L distinguished low/intermediate-risk and high-risk groups (P less than .01).

For patients who progressed within 24 months, the FLIPI-L was more predictive of progression-free survival (P = .05) than was the original FLIPI (P = .11).

Increasing FLIPI-L was an independent predictor of transformation, both when assessed as a continuous variable (P less than .01) and stepwise for FLIPI-L 3-5 (P = .004-.01). The original FLIPI, on the other hand, was not an independent predictor of transformation.

“Our analysis of a lymphopenia cutoff as an addition to the original FLIPI is simple yet improves risk stratification to differentiate between prognostic groups and, importantly, to predict transformation,” Dr. Yang and his colleagues wrote.

The authors reported having no conflicts of interest.
 

[email protected]

SOURCE: Yang G et al. Blood Cancer J. 2020 Jan 2;9(12):104. doi: 10.1038/s41408-019-0269-6.

Incorporating lymphopenia into the Follicular Lymphoma International Prognostic Index (FLIPI) can improve prognostication, according to researchers.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

The team added lymphopenia as a point in a revised FLIPI scoring system, called FLIPI-L, and found the new system could better predict overall survival (OS), progression-free survival, and histologic transformation in patients with follicular lymphoma.

George Yang, MD, of Moffitt Cancer Center in Tampa, Fla., and his colleagues described results with the FLIPI-L in a letter published in Blood Cancer Journal.

“Prior studies have demonstrated that lymphopenia was associated with worsened OS in [follicular lymphoma],” Dr. Yang and his colleagues wrote. “Therefore, we hypothesized that lymphopenia may be integrated with existing FLIPI to better stratify long-term survival outcomes and predict for transformation.”

The researchers tested this theory in 736 follicular lymphoma patients who were followed for a median of 72 months (range, 2-211 months). The 5-year OS in this cohort was 81.3%, the 10-year OS was 67.3%, and 18% of patients experienced transformation to high-grade lymphoma.

The researchers defined absolute lymphopenia as less than 1.0 × 10⁹ lymphocytes per liter. In multivariate analyses, lymphopenia was an independent predictor of OS (hazard ratio, 1.74; P less than .01) and transformation (odds ratio, 2.1; P less than .01).

To incorporate lymphopenia into the FLIPI, the researchers created a model in which 1 point was given for each of the standard FLIPI components (age, Ann Arbor stage, number of nodal areas, lactate dehydrogenase, and hemoglobin level), and one point was given for the presence of lymphopenia. Patients in the low-risk FLIPI-L category had 0-1 points, those in the intermediate-risk category had 2-3 points, and patients in the high-risk FLIPI-L category had 4-6 points.

Using the original FLIPI, the 5-year OS was 91% in the low-risk group (0-1), 82.7% in the intermediate-risk group (2), and 66% in the high-risk group (3-5). The 10-year OS was 80.4%, 66%, and 45.8%, respectively.

Using the FLIPI-L, the 5-year OS was 94.5% in the low-risk group (0-1), 89% in the intermediate-risk group (2-3), and 61% in the high-risk group (4-6). The 10-year OS was 83.9%, 68.5%, and 34.5%, respectively.

In a univariate Cox regression analysis of OS, each point increase in FLIPI-L score was associated with a significant increase in hazard ratio. For example, the hazard ratio was 3.4 for patients with a FLIPI-L score of 1 and 30.9 for those with a FLIPI-L score of 6 (P less than .02 for all FLIPI-L scores). Conversely, increases in hazard ratio were not significant with the original FLIPI (P greater than .05 for all FLIPI scores).

The FLIPI-L was prognostic for OS in different treatment groups. In patients who received rituximab alone, radiation alone, or rituximab plus chemotherapy, the scoring system differentiated low-, intermediate-, and high-risk groups (P less than .04). In patients under observation, the FLIPI-L distinguished low/intermediate-risk and high-risk groups (P less than .01).

For patients who progressed within 24 months, the FLIPI-L was more predictive of progression-free survival (P = .05) than was the original FLIPI (P = .11).

Increasing FLIPI-L was an independent predictor of transformation, both when assessed as a continuous variable (P less than .01) and stepwise for FLIPI-L 3-5 (P = .004-.01). The original FLIPI, on the other hand, was not an independent predictor of transformation.

“Our analysis of a lymphopenia cutoff as an addition to the original FLIPI is simple yet improves risk stratification to differentiate between prognostic groups and, importantly, to predict transformation,” Dr. Yang and his colleagues wrote.

The authors reported having no conflicts of interest.
 

[email protected]

SOURCE: Yang G et al. Blood Cancer J. 2020 Jan 2;9(12):104. doi: 10.1038/s41408-019-0269-6.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

[email protected]

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

[email protected]

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

[email protected]

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

Women and racial minorities with multiple myeloma may be at increased risk of delayed treatment, a situation that should be addressed urgently, according to authors of a recent analysis of a clinical oncology database.

By contrast, patients receiving myeloma treatment sooner after diagnosis included patients who were over 80 years of age, had multiple comorbidities, were treated at specialized cancer programs or in areas other than the Northeast, and had Medicaid or did not have private insurance, the authors reported.

Contrary to what was expected, levels of education and income did not significantly affect the timeliness of treatment in this analysis by Vivek Kumar, MD, of Dana-Farber Cancer Institute in Boston and coinvestigators.

While results of studies to date are “conflicting” as to whether timeliness of myeloma therapy will affect patient outcomes, recent studies in breast cancer and other tumor types suggest earlier treatment intervention may reduce morbidity, improve quality of life, and possibly prolong survival, according to Dr. Kumar and colleagues.

Moreover, the focus of myeloma treatment has shifted toward earlier treatment in light of the superiority of today’s treatment options, which was demonstrated in the 2014 update of the International Myeloma Working Group (IMWG) diagnostic criteria, according to the investigators.

“The definition of active MM [multiple myeloma] has been updated so that patients who may have been considered to have smoldering MM previously are now treated sooner to prevent end-organ damage whenever possible,” said Dr. Kumar and coauthors in their report in JCO Oncology Practice.

The analysis of timely myeloma treatment was based on for 74,722 patients in the National Cancer Database who received a diagnosis of multiple myeloma between 2004 and 2015 and went on to receive systemic treatment within the first year of diagnosis.

Delay in treatment, defined as receiving antimyeloma therapy 40 or more days after diagnosis, occurred in 18,375 of those patients, or about one-quarter of the study cohort. The mean time from diagnosis to start of treatment in that group was 63 days.

Compared with patients who received treatment within 7 days of diagnosis, patients with delays in treatment were more likely to be women (odds ratio, 1.15; 95% confidence interval, 1.1-1.2) and more likely to be non-Hispanic black (OR, 1.21; 95% CI, 1.14-1.28), the investigators reported.

A previous analysis of the SEER-Medicare database suggested that certain antimyeloma agents are used later in racial and ethnic minorities, including Hispanic patients, who had the highest median time to first dose of bortezomib, Dr. Kumar and colleagues noted.

However, no report before the present one had looked at the time to overall initial treatment in racial and ethnic minorities, they added.

Patients diagnosed in more recent years had higher odds of treatment delay, though this could have been caused by an increase in the number of patients diagnosed early; prior to the 2014 IMWG diagnostic criteria revision, many would have been offered therapy only when signs of end-organ damage were present, while patients without end-organ damage would have been said to have smoldering disease, authors said.

Patients 80 years of age and older and those with a higher Charlson comorbidity score had a lower likelihood of treatment delay in this analysis, possibly reflecting the frailty of those patients and an urgent need for treatment, according to investigators.

Uninsured patients and those with Medicaid were less likely than insured patients to experience treatment delay, according to the report.

“This may be associated with the fact that, for these insurances, prior authorization is typically not required before initiating treatment,” said Dr. Kumar and colleagues. “However, this could also depend on several other possible factors, including availability of caregiver support and seeking medical care later.”

Dr. Kumar reported no conflicts of interest related to the analysis. Coauthors reported disclosures with Takeda, Guardant Health, and other pharmaceutical companies.

SOURCE: Kumar V et al. JCO Oncology Practice. 2020 Jan 21. doi: 10.1200/JOP.19.00309.

Women and racial minorities with multiple myeloma may be at increased risk of delayed treatment, a situation that should be addressed urgently, according to authors of a recent analysis of a clinical oncology database.

By contrast, patients receiving myeloma treatment sooner after diagnosis included patients who were over 80 years of age, had multiple comorbidities, were treated at specialized cancer programs or in areas other than the Northeast, and had Medicaid or did not have private insurance, the authors reported.

Contrary to what was expected, levels of education and income did not significantly affect the timeliness of treatment in this analysis by Vivek Kumar, MD, of Dana-Farber Cancer Institute in Boston and coinvestigators.

While results of studies to date are “conflicting” as to whether timeliness of myeloma therapy will affect patient outcomes, recent studies in breast cancer and other tumor types suggest earlier treatment intervention may reduce morbidity, improve quality of life, and possibly prolong survival, according to Dr. Kumar and colleagues.

Moreover, the focus of myeloma treatment has shifted toward earlier treatment in light of the superiority of today’s treatment options, which was demonstrated in the 2014 update of the International Myeloma Working Group (IMWG) diagnostic criteria, according to the investigators.

“The definition of active MM [multiple myeloma] has been updated so that patients who may have been considered to have smoldering MM previously are now treated sooner to prevent end-organ damage whenever possible,” said Dr. Kumar and coauthors in their report in JCO Oncology Practice.

The analysis of timely myeloma treatment was based on for 74,722 patients in the National Cancer Database who received a diagnosis of multiple myeloma between 2004 and 2015 and went on to receive systemic treatment within the first year of diagnosis.

Delay in treatment, defined as receiving antimyeloma therapy 40 or more days after diagnosis, occurred in 18,375 of those patients, or about one-quarter of the study cohort. The mean time from diagnosis to start of treatment in that group was 63 days.

Compared with patients who received treatment within 7 days of diagnosis, patients with delays in treatment were more likely to be women (odds ratio, 1.15; 95% confidence interval, 1.1-1.2) and more likely to be non-Hispanic black (OR, 1.21; 95% CI, 1.14-1.28), the investigators reported.

A previous analysis of the SEER-Medicare database suggested that certain antimyeloma agents are used later in racial and ethnic minorities, including Hispanic patients, who had the highest median time to first dose of bortezomib, Dr. Kumar and colleagues noted.

However, no report before the present one had looked at the time to overall initial treatment in racial and ethnic minorities, they added.

Patients diagnosed in more recent years had higher odds of treatment delay, though this could have been caused by an increase in the number of patients diagnosed early; prior to the 2014 IMWG diagnostic criteria revision, many would have been offered therapy only when signs of end-organ damage were present, while patients without end-organ damage would have been said to have smoldering disease, authors said.

Patients 80 years of age and older and those with a higher Charlson comorbidity score had a lower likelihood of treatment delay in this analysis, possibly reflecting the frailty of those patients and an urgent need for treatment, according to investigators.

Uninsured patients and those with Medicaid were less likely than insured patients to experience treatment delay, according to the report.

“This may be associated with the fact that, for these insurances, prior authorization is typically not required before initiating treatment,” said Dr. Kumar and colleagues. “However, this could also depend on several other possible factors, including availability of caregiver support and seeking medical care later.”

Dr. Kumar reported no conflicts of interest related to the analysis. Coauthors reported disclosures with Takeda, Guardant Health, and other pharmaceutical companies.

SOURCE: Kumar V et al. JCO Oncology Practice. 2020 Jan 21. doi: 10.1200/JOP.19.00309.

Women and racial minorities with multiple myeloma may be at increased risk of delayed treatment, a situation that should be addressed urgently, according to authors of a recent analysis of a clinical oncology database.

By contrast, patients receiving myeloma treatment sooner after diagnosis included patients who were over 80 years of age, had multiple comorbidities, were treated at specialized cancer programs or in areas other than the Northeast, and had Medicaid or did not have private insurance, the authors reported.

Contrary to what was expected, levels of education and income did not significantly affect the timeliness of treatment in this analysis by Vivek Kumar, MD, of Dana-Farber Cancer Institute in Boston and coinvestigators.

While results of studies to date are “conflicting” as to whether timeliness of myeloma therapy will affect patient outcomes, recent studies in breast cancer and other tumor types suggest earlier treatment intervention may reduce morbidity, improve quality of life, and possibly prolong survival, according to Dr. Kumar and colleagues.

Moreover, the focus of myeloma treatment has shifted toward earlier treatment in light of the superiority of today’s treatment options, which was demonstrated in the 2014 update of the International Myeloma Working Group (IMWG) diagnostic criteria, according to the investigators.

“The definition of active MM [multiple myeloma] has been updated so that patients who may have been considered to have smoldering MM previously are now treated sooner to prevent end-organ damage whenever possible,” said Dr. Kumar and coauthors in their report in JCO Oncology Practice.

The analysis of timely myeloma treatment was based on for 74,722 patients in the National Cancer Database who received a diagnosis of multiple myeloma between 2004 and 2015 and went on to receive systemic treatment within the first year of diagnosis.

Delay in treatment, defined as receiving antimyeloma therapy 40 or more days after diagnosis, occurred in 18,375 of those patients, or about one-quarter of the study cohort. The mean time from diagnosis to start of treatment in that group was 63 days.

Compared with patients who received treatment within 7 days of diagnosis, patients with delays in treatment were more likely to be women (odds ratio, 1.15; 95% confidence interval, 1.1-1.2) and more likely to be non-Hispanic black (OR, 1.21; 95% CI, 1.14-1.28), the investigators reported.

A previous analysis of the SEER-Medicare database suggested that certain antimyeloma agents are used later in racial and ethnic minorities, including Hispanic patients, who had the highest median time to first dose of bortezomib, Dr. Kumar and colleagues noted.

However, no report before the present one had looked at the time to overall initial treatment in racial and ethnic minorities, they added.

Patients diagnosed in more recent years had higher odds of treatment delay, though this could have been caused by an increase in the number of patients diagnosed early; prior to the 2014 IMWG diagnostic criteria revision, many would have been offered therapy only when signs of end-organ damage were present, while patients without end-organ damage would have been said to have smoldering disease, authors said.

Patients 80 years of age and older and those with a higher Charlson comorbidity score had a lower likelihood of treatment delay in this analysis, possibly reflecting the frailty of those patients and an urgent need for treatment, according to investigators.

Uninsured patients and those with Medicaid were less likely than insured patients to experience treatment delay, according to the report.

“This may be associated with the fact that, for these insurances, prior authorization is typically not required before initiating treatment,” said Dr. Kumar and colleagues. “However, this could also depend on several other possible factors, including availability of caregiver support and seeking medical care later.”

Dr. Kumar reported no conflicts of interest related to the analysis. Coauthors reported disclosures with Takeda, Guardant Health, and other pharmaceutical companies.

SOURCE: Kumar V et al. JCO Oncology Practice. 2020 Jan 21. doi: 10.1200/JOP.19.00309.

ORLANDO – Sevuparin, a novel nonanticoagulant heparinoid drug, showed no efficacy for acute vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD) in the randomized, controlled, phase 2 TVOC01 trial, but its promising safety and broad mechanism of action warrant further exploration in the prodromal VOC setting, according to investigators.

Dr_Microbe/Thinkstock

Time to VOC resolution – the primary study endpoint – was similar at about 168 hours in 71 hospitalized patients randomized to receive sevuparin and in 76 who received placebo (intention-to-treat hazard ratio, 0.89), Bart J. Biemond, MD, explained during a presentation of the findings at the annual meeting of the American Society of Hematology.

A per-protocol analysis based on the 69 and 75 patients dosed in the treatment and placebo arms, respectively, showed a similar result (HR, 0.81), said Dr. Biemond of the department of clinical hematology, Amsterdam UMC, Academic Medical Center, the Netherlands.

Secondary endpoints, including mean change in pain intensity from baseline on a visual analogue scale (VAS), duration of severest pain measured as time to achieve a 30% reduction in VAS score from baseline, and cumulative use of parenteral opioids, also did not differ between the treatment and placebo arms, he added.

Patients in the global, double-blind, multicenter trial were aged 12-50 years (median, 22 years) with any type of SCD. They were enrolled from 16 sites in 7 countries to receive a loading dose of 3 mg/kg of sevuparin and continuous 18 mg/kg per day infusions or placebo. Patients in both arms also received standard-of-care and parenteral opioid therapy.

The groups were generally balanced with respect to demographic and baseline characteristics, Dr. Biemond said, noting that the treatment was safe: No serious adverse events occurred, and any mild-to-moderate adverse events were transient.

The findings were disappointing given the lack of approved treatment options other than pain management for acute VOC in hospitalized patients with SCD, and they were somewhat surprising given that preclinical and clinical data in recent years have demonstrated that “you can actually prevent those crises by antiadhesive strategies,” he said.

“So we hypothesized that, if you perform such an antiadhesive strategy in a patient already having a crisis and admitted in the hospital, you may shorten their period of admission and perhaps also shorten the severity of their pain,” he said.

In fact, a single-center, randomized, controlled trial conducted by Qari et al. in 2007 (Thromb Haemost. 2007 Aug;98[2]:392-6) showed that full-dose tinzaparin reduced pain severity and duration of admission among sickle cell patients with acute VOC – perhaps because of the antiadhesive properties of heparin – but that study was never repeated, Dr. Biemond said, noting that those antiadhesive properties have been well documented in animal studies.

“Heparin is able to inhibit P-selectin, L-selectin, thrombospondin, fibronectin, and von Willebrand activity, which are all involved in vaso-occlusion in patients with sickle cell disease, and very likely also involved during a vaso-occlusive crisis,” he explained, adding that sevuparin, a low-molecular-weight heparin without functional antithrombin binding domain, seemed to be a good candidate for testing that hypothesis.

“It has no anticoagulant effects on factor Xa and IIa,” he said. “It retains, however, its antiadhesive and antiaggregation properties.”

Since it has no anticoagulation activity, it can be dosed at up to 20-fold the therapeutic dose of low-molecular-weight heparin to optimize the antiadhesive effects, he noted.

However, the data indicate that “antiadhesive therapies are clearly not effective in patients with vaso-occlusive crisis,” he said, noting that this was also affirmed by a similar 2019 study of the investigational panselectin inhibitor rivipansel, as reported in a Pfizer press release.

Intriguingly, the difference between the current study and the 2007 study by Qari et al. raises questions about whether anticoagulation, rather than antiadhesion, helped resolve VOC in that study, he said, noting that future studies should focus on whether that is the case.

As for the role of antiadhesive therapy, the mode of action of sevuparin and the current findings taken together suggest that future studies should also assess whether it can be used to prevent VOC.

“Perhaps sevuparin could be administered to patients in a prodromal phase – just before a real vaso-occlusive crisis appears – to prevent such a crisis from happening,” he said. “It would be interesting to use the drug that way.”

Dr. Biemond reported research funding from Sanquin and honoraria from Novartis and GBT.

[email protected]

SOURCE: Biemond B et al. ASH 2019, Abstract 614.

ORLANDO – Sevuparin, a novel nonanticoagulant heparinoid drug, showed no efficacy for acute vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD) in the randomized, controlled, phase 2 TVOC01 trial, but its promising safety and broad mechanism of action warrant further exploration in the prodromal VOC setting, according to investigators.

Dr_Microbe/Thinkstock

Time to VOC resolution – the primary study endpoint – was similar at about 168 hours in 71 hospitalized patients randomized to receive sevuparin and in 76 who received placebo (intention-to-treat hazard ratio, 0.89), Bart J. Biemond, MD, explained during a presentation of the findings at the annual meeting of the American Society of Hematology.

A per-protocol analysis based on the 69 and 75 patients dosed in the treatment and placebo arms, respectively, showed a similar result (HR, 0.81), said Dr. Biemond of the department of clinical hematology, Amsterdam UMC, Academic Medical Center, the Netherlands.

Secondary endpoints, including mean change in pain intensity from baseline on a visual analogue scale (VAS), duration of severest pain measured as time to achieve a 30% reduction in VAS score from baseline, and cumulative use of parenteral opioids, also did not differ between the treatment and placebo arms, he added.

Patients in the global, double-blind, multicenter trial were aged 12-50 years (median, 22 years) with any type of SCD. They were enrolled from 16 sites in 7 countries to receive a loading dose of 3 mg/kg of sevuparin and continuous 18 mg/kg per day infusions or placebo. Patients in both arms also received standard-of-care and parenteral opioid therapy.

The groups were generally balanced with respect to demographic and baseline characteristics, Dr. Biemond said, noting that the treatment was safe: No serious adverse events occurred, and any mild-to-moderate adverse events were transient.

The findings were disappointing given the lack of approved treatment options other than pain management for acute VOC in hospitalized patients with SCD, and they were somewhat surprising given that preclinical and clinical data in recent years have demonstrated that “you can actually prevent those crises by antiadhesive strategies,” he said.

“So we hypothesized that, if you perform such an antiadhesive strategy in a patient already having a crisis and admitted in the hospital, you may shorten their period of admission and perhaps also shorten the severity of their pain,” he said.

In fact, a single-center, randomized, controlled trial conducted by Qari et al. in 2007 (Thromb Haemost. 2007 Aug;98[2]:392-6) showed that full-dose tinzaparin reduced pain severity and duration of admission among sickle cell patients with acute VOC – perhaps because of the antiadhesive properties of heparin – but that study was never repeated, Dr. Biemond said, noting that those antiadhesive properties have been well documented in animal studies.

“Heparin is able to inhibit P-selectin, L-selectin, thrombospondin, fibronectin, and von Willebrand activity, which are all involved in vaso-occlusion in patients with sickle cell disease, and very likely also involved during a vaso-occlusive crisis,” he explained, adding that sevuparin, a low-molecular-weight heparin without functional antithrombin binding domain, seemed to be a good candidate for testing that hypothesis.

“It has no anticoagulant effects on factor Xa and IIa,” he said. “It retains, however, its antiadhesive and antiaggregation properties.”

Since it has no anticoagulation activity, it can be dosed at up to 20-fold the therapeutic dose of low-molecular-weight heparin to optimize the antiadhesive effects, he noted.

However, the data indicate that “antiadhesive therapies are clearly not effective in patients with vaso-occlusive crisis,” he said, noting that this was also affirmed by a similar 2019 study of the investigational panselectin inhibitor rivipansel, as reported in a Pfizer press release.

Intriguingly, the difference between the current study and the 2007 study by Qari et al. raises questions about whether anticoagulation, rather than antiadhesion, helped resolve VOC in that study, he said, noting that future studies should focus on whether that is the case.

As for the role of antiadhesive therapy, the mode of action of sevuparin and the current findings taken together suggest that future studies should also assess whether it can be used to prevent VOC.

“Perhaps sevuparin could be administered to patients in a prodromal phase – just before a real vaso-occlusive crisis appears – to prevent such a crisis from happening,” he said. “It would be interesting to use the drug that way.”

Dr. Biemond reported research funding from Sanquin and honoraria from Novartis and GBT.

[email protected]

SOURCE: Biemond B et al. ASH 2019, Abstract 614.

ORLANDO – Sevuparin, a novel nonanticoagulant heparinoid drug, showed no efficacy for acute vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD) in the randomized, controlled, phase 2 TVOC01 trial, but its promising safety and broad mechanism of action warrant further exploration in the prodromal VOC setting, according to investigators.

Dr_Microbe/Thinkstock

Time to VOC resolution – the primary study endpoint – was similar at about 168 hours in 71 hospitalized patients randomized to receive sevuparin and in 76 who received placebo (intention-to-treat hazard ratio, 0.89), Bart J. Biemond, MD, explained during a presentation of the findings at the annual meeting of the American Society of Hematology.

A per-protocol analysis based on the 69 and 75 patients dosed in the treatment and placebo arms, respectively, showed a similar result (HR, 0.81), said Dr. Biemond of the department of clinical hematology, Amsterdam UMC, Academic Medical Center, the Netherlands.

Secondary endpoints, including mean change in pain intensity from baseline on a visual analogue scale (VAS), duration of severest pain measured as time to achieve a 30% reduction in VAS score from baseline, and cumulative use of parenteral opioids, also did not differ between the treatment and placebo arms, he added.

Patients in the global, double-blind, multicenter trial were aged 12-50 years (median, 22 years) with any type of SCD. They were enrolled from 16 sites in 7 countries to receive a loading dose of 3 mg/kg of sevuparin and continuous 18 mg/kg per day infusions or placebo. Patients in both arms also received standard-of-care and parenteral opioid therapy.

The groups were generally balanced with respect to demographic and baseline characteristics, Dr. Biemond said, noting that the treatment was safe: No serious adverse events occurred, and any mild-to-moderate adverse events were transient.

The findings were disappointing given the lack of approved treatment options other than pain management for acute VOC in hospitalized patients with SCD, and they were somewhat surprising given that preclinical and clinical data in recent years have demonstrated that “you can actually prevent those crises by antiadhesive strategies,” he said.

“So we hypothesized that, if you perform such an antiadhesive strategy in a patient already having a crisis and admitted in the hospital, you may shorten their period of admission and perhaps also shorten the severity of their pain,” he said.

In fact, a single-center, randomized, controlled trial conducted by Qari et al. in 2007 (Thromb Haemost. 2007 Aug;98[2]:392-6) showed that full-dose tinzaparin reduced pain severity and duration of admission among sickle cell patients with acute VOC – perhaps because of the antiadhesive properties of heparin – but that study was never repeated, Dr. Biemond said, noting that those antiadhesive properties have been well documented in animal studies.

“Heparin is able to inhibit P-selectin, L-selectin, thrombospondin, fibronectin, and von Willebrand activity, which are all involved in vaso-occlusion in patients with sickle cell disease, and very likely also involved during a vaso-occlusive crisis,” he explained, adding that sevuparin, a low-molecular-weight heparin without functional antithrombin binding domain, seemed to be a good candidate for testing that hypothesis.

“It has no anticoagulant effects on factor Xa and IIa,” he said. “It retains, however, its antiadhesive and antiaggregation properties.”

Since it has no anticoagulation activity, it can be dosed at up to 20-fold the therapeutic dose of low-molecular-weight heparin to optimize the antiadhesive effects, he noted.

However, the data indicate that “antiadhesive therapies are clearly not effective in patients with vaso-occlusive crisis,” he said, noting that this was also affirmed by a similar 2019 study of the investigational panselectin inhibitor rivipansel, as reported in a Pfizer press release.

Intriguingly, the difference between the current study and the 2007 study by Qari et al. raises questions about whether anticoagulation, rather than antiadhesion, helped resolve VOC in that study, he said, noting that future studies should focus on whether that is the case.

As for the role of antiadhesive therapy, the mode of action of sevuparin and the current findings taken together suggest that future studies should also assess whether it can be used to prevent VOC.

“Perhaps sevuparin could be administered to patients in a prodromal phase – just before a real vaso-occlusive crisis appears – to prevent such a crisis from happening,” he said. “It would be interesting to use the drug that way.”

Dr. Biemond reported research funding from Sanquin and honoraria from Novartis and GBT.

[email protected]

SOURCE: Biemond B et al. ASH 2019, Abstract 614.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.

Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.

Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.

“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.

“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
 

Baseline characteristics and treatment

Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.

Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.

Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.

The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).

GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
 

Outcomes

Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).

Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).

Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
 

Potential drivers of outcome

Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.

Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”

The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”

“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”

Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.

“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”

Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.

This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.

[email protected]

SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
 

A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.

Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.

Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.

“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.

“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
 

Baseline characteristics and treatment

Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.

Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.

Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.

The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).

GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
 

Outcomes

Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).

Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).

Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
 

Potential drivers of outcome

Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.

Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”

The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”

“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”

Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.

“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”

Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.

This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.

[email protected]

SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
 

A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.

Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.

Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.

“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.

“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
 

Baseline characteristics and treatment

Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.

Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.

Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.

The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).

GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
 

Outcomes

Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).

Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).

Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
 

Potential drivers of outcome

Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.

Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”

The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”

“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”

Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.

“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”

Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.

This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.

[email protected]

SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.