ALL: Excess weight linked to much worse outcomes

A new study offers a grim portrait of the apparent effects of excess weight on outcomes in acute lymphoblastic leukemia (ALL): Among patients aged 15-50 years who were treated with asparaginase-containing pediatric regimens, mortality and treatment-related side effects were much more common in those with elevated body mass index (BMI). Older obese/overweight patients were especially likely to have poor outcomes.

The study, published in Blood Advances, doesn’t identify a culprit behind the worse outcomes in obese and overweight patients. However, it does highlight the limits of asparaginase-containing pediatric regimens in these patients, said study senior author and Dana-Farber Cancer Institute leukemia specialist Marlise R. Luskin, MD, in an interview.

“Pediatric-inspired regimens can be applied safely in adults up to the age of 50 years, with those of normal BMI having particularly good outcomes. Further research is needed to determine the best approach to treating patients of all ages with elevated BMIs,” Dr. Luskin said.

ALL is an uncommon cancer that kills about 1,390 people in the United States each year, according to the American Cancer Society. Most cases are in children, but most deaths are in adults, according to the ACS.

Research over the past 20 years has shown that younger adults “with ALL have better outcomes when they treated with intensive pediatric-style chemotherapy regimens than when they are treated with traditional adult regimens,” Dr. Luskin said. “Still, too many young adults do not have good outcomes. Either their disease is resistant to chemotherapy, or they experience significant side effects from treatment. Our main motivation for this study was to better understand which adolescents and younger adults have good outcomes with pediatric-style chemotherapy, and which patients require improved approaches.”

The researchers retrospectively tracked 388 patients aged 15-50 who were treated with Dana-Farber Consortium regimens from 2001 to 2021. A total of 46.7% were overweight or obese as defined by BMI. Of the rest, 2.6% were underweight, and 50.7% had normal weight. The study defined this combined group (53.3%) as having normal weight.

Most patients were male (61.9%), the median age was 24 years, and 35% were aged 30-50. All were treated with asparaginase-based regimens, although the components of the regimens changed over time.

In a bit of good news, “the study remarkably found equivalent overall survival among younger (aged 15-29) and older (aged 30-50) patients with normal BMI – 83% versus 85%, respectively [P = .89],” said lead author and Dana-Farber Cancer Institute advanced leukemia fellow Shai Shimony, MD. “This is an incredibly important finding as many are hesitant to offer pediatric regimens to patients over 30 years merely because of their age.”

As for differences by weight, both the normal and overweight/obese groups had identical rates of remission (87%; P = .84). However, overweight or obese patients had higher 4-year non-relapse mortality (11.7% vs. 2.8%; P = .006), worse event-free 4-year survival (63% vs. 77%; P = .003), and worse overall 4-year survival (64% vs. 83%; P = .0001).

Older obese/overweight patients (aged 30-50) were especially vulnerable to death, with worse overall 4-year survival versus their younger counterparts (55% vs. 73%; P = .023).

In another finding, the researchers also found that high triglyceride levels were common in patients, and this was linked to improved survival and decreased risk of relapse. These higher levels are likely linked to the drug regimen and “are not in and of themselves harmful or a reason to discontinue treatment,” Dr. Luskin said.

As for treatment-related side effects, an analysis of 353 patients found that grade III/IV hepatotoxicity – defined as elevation of AST, ALT, and/or bilirubin – was higher in patients who were overweight/obese versus normal weight (60.7% vs. 42.2%; P = .0005). Grade III/IV hyperglycemias were also higher in the overweight/obese group vs. normal weight (36.4% vs. 24.4%; P = .014).

Why might excess weight lead to worse outcomes? “We found that BMI was associated with more nonrelapse mortality, meaning death due to treatment-related side effects,” said Dr. Shimony. “This may be because patients with higher BMI are less able to tolerate chemotherapy, possibly due to more hyperglycemia, infection, and less overall resilience in the setting of complications. Obesity may also be associated with intrinsic disease resistance. This may be because adipose tissue protects lymphoblasts from the effects of chemotherapy or is due to underdosing of chemotherapy drugs.”

The study authors noted limitations to their research such as its reliance on BMI at diagnosis, without details about weight changes over time, and the lack of a systematic evaluation of measurable residual disease.

In an interview, Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, said it’s indeed possible that heavier patients may be underdosed with chemotherapy – especially older ones who may have more excess weight than children.

Dr. Nichols, who praised the study, highlighted another theory. “What causes you metabolically to be overweight may be connected to some reason to less metabolization of chemotherapy drugs,” she said.

Going forward, Dr. Shimony said “clinicians treating younger adults with ALL should monitor their patients with elevated BMI very closely for response and side effects. We recommend these patients be enrolled in clinical trials whenever possible so that more can be learned about how this group of patients responds to novel treatment approaches. Importantly, it is not yet known how obesity is associated with outcomes in nonasparaginase regimens such as hyper-CVAD or those approaches that rely on novel agents.” 

The Foley Family Research Fund funded the study. Dr. Luskin disclosed research support from Abbvie and Novartis, and some other study authors reported various disclosures. Dr. Shimony and Dr. Nichols have no disclosures.
 

A new study offers a grim portrait of the apparent effects of excess weight on outcomes in acute lymphoblastic leukemia (ALL): Among patients aged 15-50 years who were treated with asparaginase-containing pediatric regimens, mortality and treatment-related side effects were much more common in those with elevated body mass index (BMI). Older obese/overweight patients were especially likely to have poor outcomes.

The study, published in Blood Advances, doesn’t identify a culprit behind the worse outcomes in obese and overweight patients. However, it does highlight the limits of asparaginase-containing pediatric regimens in these patients, said study senior author and Dana-Farber Cancer Institute leukemia specialist Marlise R. Luskin, MD, in an interview.

“Pediatric-inspired regimens can be applied safely in adults up to the age of 50 years, with those of normal BMI having particularly good outcomes. Further research is needed to determine the best approach to treating patients of all ages with elevated BMIs,” Dr. Luskin said.

ALL is an uncommon cancer that kills about 1,390 people in the United States each year, according to the American Cancer Society. Most cases are in children, but most deaths are in adults, according to the ACS.

Research over the past 20 years has shown that younger adults “with ALL have better outcomes when they treated with intensive pediatric-style chemotherapy regimens than when they are treated with traditional adult regimens,” Dr. Luskin said. “Still, too many young adults do not have good outcomes. Either their disease is resistant to chemotherapy, or they experience significant side effects from treatment. Our main motivation for this study was to better understand which adolescents and younger adults have good outcomes with pediatric-style chemotherapy, and which patients require improved approaches.”

The researchers retrospectively tracked 388 patients aged 15-50 who were treated with Dana-Farber Consortium regimens from 2001 to 2021. A total of 46.7% were overweight or obese as defined by BMI. Of the rest, 2.6% were underweight, and 50.7% had normal weight. The study defined this combined group (53.3%) as having normal weight.

Most patients were male (61.9%), the median age was 24 years, and 35% were aged 30-50. All were treated with asparaginase-based regimens, although the components of the regimens changed over time.

In a bit of good news, “the study remarkably found equivalent overall survival among younger (aged 15-29) and older (aged 30-50) patients with normal BMI – 83% versus 85%, respectively [P = .89],” said lead author and Dana-Farber Cancer Institute advanced leukemia fellow Shai Shimony, MD. “This is an incredibly important finding as many are hesitant to offer pediatric regimens to patients over 30 years merely because of their age.”

As for differences by weight, both the normal and overweight/obese groups had identical rates of remission (87%; P = .84). However, overweight or obese patients had higher 4-year non-relapse mortality (11.7% vs. 2.8%; P = .006), worse event-free 4-year survival (63% vs. 77%; P = .003), and worse overall 4-year survival (64% vs. 83%; P = .0001).

Older obese/overweight patients (aged 30-50) were especially vulnerable to death, with worse overall 4-year survival versus their younger counterparts (55% vs. 73%; P = .023).

In another finding, the researchers also found that high triglyceride levels were common in patients, and this was linked to improved survival and decreased risk of relapse. These higher levels are likely linked to the drug regimen and “are not in and of themselves harmful or a reason to discontinue treatment,” Dr. Luskin said.

As for treatment-related side effects, an analysis of 353 patients found that grade III/IV hepatotoxicity – defined as elevation of AST, ALT, and/or bilirubin – was higher in patients who were overweight/obese versus normal weight (60.7% vs. 42.2%; P = .0005). Grade III/IV hyperglycemias were also higher in the overweight/obese group vs. normal weight (36.4% vs. 24.4%; P = .014).

Why might excess weight lead to worse outcomes? “We found that BMI was associated with more nonrelapse mortality, meaning death due to treatment-related side effects,” said Dr. Shimony. “This may be because patients with higher BMI are less able to tolerate chemotherapy, possibly due to more hyperglycemia, infection, and less overall resilience in the setting of complications. Obesity may also be associated with intrinsic disease resistance. This may be because adipose tissue protects lymphoblasts from the effects of chemotherapy or is due to underdosing of chemotherapy drugs.”

The study authors noted limitations to their research such as its reliance on BMI at diagnosis, without details about weight changes over time, and the lack of a systematic evaluation of measurable residual disease.

In an interview, Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, said it’s indeed possible that heavier patients may be underdosed with chemotherapy – especially older ones who may have more excess weight than children.

Dr. Nichols, who praised the study, highlighted another theory. “What causes you metabolically to be overweight may be connected to some reason to less metabolization of chemotherapy drugs,” she said.

Going forward, Dr. Shimony said “clinicians treating younger adults with ALL should monitor their patients with elevated BMI very closely for response and side effects. We recommend these patients be enrolled in clinical trials whenever possible so that more can be learned about how this group of patients responds to novel treatment approaches. Importantly, it is not yet known how obesity is associated with outcomes in nonasparaginase regimens such as hyper-CVAD or those approaches that rely on novel agents.” 

The Foley Family Research Fund funded the study. Dr. Luskin disclosed research support from Abbvie and Novartis, and some other study authors reported various disclosures. Dr. Shimony and Dr. Nichols have no disclosures.
 

A new study offers a grim portrait of the apparent effects of excess weight on outcomes in acute lymphoblastic leukemia (ALL): Among patients aged 15-50 years who were treated with asparaginase-containing pediatric regimens, mortality and treatment-related side effects were much more common in those with elevated body mass index (BMI). Older obese/overweight patients were especially likely to have poor outcomes.

The study, published in Blood Advances, doesn’t identify a culprit behind the worse outcomes in obese and overweight patients. However, it does highlight the limits of asparaginase-containing pediatric regimens in these patients, said study senior author and Dana-Farber Cancer Institute leukemia specialist Marlise R. Luskin, MD, in an interview.

“Pediatric-inspired regimens can be applied safely in adults up to the age of 50 years, with those of normal BMI having particularly good outcomes. Further research is needed to determine the best approach to treating patients of all ages with elevated BMIs,” Dr. Luskin said.

ALL is an uncommon cancer that kills about 1,390 people in the United States each year, according to the American Cancer Society. Most cases are in children, but most deaths are in adults, according to the ACS.

Research over the past 20 years has shown that younger adults “with ALL have better outcomes when they treated with intensive pediatric-style chemotherapy regimens than when they are treated with traditional adult regimens,” Dr. Luskin said. “Still, too many young adults do not have good outcomes. Either their disease is resistant to chemotherapy, or they experience significant side effects from treatment. Our main motivation for this study was to better understand which adolescents and younger adults have good outcomes with pediatric-style chemotherapy, and which patients require improved approaches.”

The researchers retrospectively tracked 388 patients aged 15-50 who were treated with Dana-Farber Consortium regimens from 2001 to 2021. A total of 46.7% were overweight or obese as defined by BMI. Of the rest, 2.6% were underweight, and 50.7% had normal weight. The study defined this combined group (53.3%) as having normal weight.

Most patients were male (61.9%), the median age was 24 years, and 35% were aged 30-50. All were treated with asparaginase-based regimens, although the components of the regimens changed over time.

In a bit of good news, “the study remarkably found equivalent overall survival among younger (aged 15-29) and older (aged 30-50) patients with normal BMI – 83% versus 85%, respectively [P = .89],” said lead author and Dana-Farber Cancer Institute advanced leukemia fellow Shai Shimony, MD. “This is an incredibly important finding as many are hesitant to offer pediatric regimens to patients over 30 years merely because of their age.”

As for differences by weight, both the normal and overweight/obese groups had identical rates of remission (87%; P = .84). However, overweight or obese patients had higher 4-year non-relapse mortality (11.7% vs. 2.8%; P = .006), worse event-free 4-year survival (63% vs. 77%; P = .003), and worse overall 4-year survival (64% vs. 83%; P = .0001).

Older obese/overweight patients (aged 30-50) were especially vulnerable to death, with worse overall 4-year survival versus their younger counterparts (55% vs. 73%; P = .023).

In another finding, the researchers also found that high triglyceride levels were common in patients, and this was linked to improved survival and decreased risk of relapse. These higher levels are likely linked to the drug regimen and “are not in and of themselves harmful or a reason to discontinue treatment,” Dr. Luskin said.

As for treatment-related side effects, an analysis of 353 patients found that grade III/IV hepatotoxicity – defined as elevation of AST, ALT, and/or bilirubin – was higher in patients who were overweight/obese versus normal weight (60.7% vs. 42.2%; P = .0005). Grade III/IV hyperglycemias were also higher in the overweight/obese group vs. normal weight (36.4% vs. 24.4%; P = .014).

Why might excess weight lead to worse outcomes? “We found that BMI was associated with more nonrelapse mortality, meaning death due to treatment-related side effects,” said Dr. Shimony. “This may be because patients with higher BMI are less able to tolerate chemotherapy, possibly due to more hyperglycemia, infection, and less overall resilience in the setting of complications. Obesity may also be associated with intrinsic disease resistance. This may be because adipose tissue protects lymphoblasts from the effects of chemotherapy or is due to underdosing of chemotherapy drugs.”

The study authors noted limitations to their research such as its reliance on BMI at diagnosis, without details about weight changes over time, and the lack of a systematic evaluation of measurable residual disease.

In an interview, Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, said it’s indeed possible that heavier patients may be underdosed with chemotherapy – especially older ones who may have more excess weight than children.

Dr. Nichols, who praised the study, highlighted another theory. “What causes you metabolically to be overweight may be connected to some reason to less metabolization of chemotherapy drugs,” she said.

Going forward, Dr. Shimony said “clinicians treating younger adults with ALL should monitor their patients with elevated BMI very closely for response and side effects. We recommend these patients be enrolled in clinical trials whenever possible so that more can be learned about how this group of patients responds to novel treatment approaches. Importantly, it is not yet known how obesity is associated with outcomes in nonasparaginase regimens such as hyper-CVAD or those approaches that rely on novel agents.” 

The Foley Family Research Fund funded the study. Dr. Luskin disclosed research support from Abbvie and Novartis, and some other study authors reported various disclosures. Dr. Shimony and Dr. Nichols have no disclosures.