An elevated body mass index (BMI) could potentially be associated with inferior treatment outcomes in adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL), according to a new study published by Shimony et al in Blood Advances. The findings may demonstrate the impact of weight on treatment toxicities and outcomes.

Background

Obesity is a growing public health threat in the United States, affecting approximately 40% of the population as of 2020. Defined by a higher BMI, obesity may play an adverse role in AYA patients’ responses to ALL treatment regimens.

“We have known for roughly 15 years that obesity affects survival in pediatric patients treated for ALL, and more recently, we are recognizing a similar relationship in adult populations,” stressed lead study author Shai Shimony, MD, an advanced clinical fellow in the Department of Leukemia at the Dana-Farber Cancer Institute. “But we wanted more granular data on this, to understand why this correlation exists, and how dependent it is on age,” he added.

Study Methods and Results

In the new study, investigators examined the relationship between BMI, age, toxicities, and treatment outcomes among 388 AYA patients aged 15 to 50 years who were treated for ALL between 2008 and 2021—with the goal of identifying correlations and trends.

The investigators reported that 53.3% of AYA patients involved in the study had a normal BMI, whereas 46.6% of them had overweight or obesity. Notably, patients with an overweight or obese BMI exhibited a higher nonrelapse mortality rate (11.7% vs 2.8%), lower event-free survival rate after 4 years of follow-up (63% vs 77%), and worse overall survival rate (64% vs 83%) compared with those who had a normal BMI. The investigators found similar overall survival rates among patients aged 15 to 29 and those aged 30 to 50 with a normal BMI (83% vs 85%, respectively)—a significant finding, since age is often considered an adverse prognostic feature in ALL.

Further, the investigators discovered that the main factor driving worse outcomes was nonrelapse mortality rather than disease relapse. Regarding toxicities, compared with those who had a normal BMI, patients who had overweight or obesity more frequently presented with elevated liver enzymes (60.7% vs 42.2%) and glucose levels (36.4% vs 24.4%).

In the multivariable model, higher BMI was associated with worse survival, whereas elevated triglycerides were associated with improved survival and age was not associated with survival. Elevated triglycerides reflect the activity of the chemotherapy agent asparaginase—which was included in the regimen—and represents the possibility of using this affordable lab test as a biomarker of treatment efficacy. However, the investigators noted that this should not be viewed as an adverse finding.

Conclusions

“This study highlights the association between elevated BMI and increased treatment-related toxicity, nonrelapse mortality, and decreased overall survival in AYA [patients] undergoing treatment for ALL with intensive pediatric regimens,” emphasized Dr. Shimony.

The investigators underscored that the retrospective nature of the study, the absence of data on measurable residual disease outcomes, and the majority White population may have posed limitations on the research. Additionally, BMI—as well as other measures of obesity such as waist circumference, and waist-to-hip ratio—should be prospectively collected and correlated with outcomes in multiple treatment contexts, including patients of all ages and those starting new regimens that incorporate novel therapies.

The investigators suggested that further studies analyzing of the impact of weight on responses to different ALL chemotherapy regimens may be needed.

“Moving forward, we hope that measures of obesity will be considered a vital variable in determining the most suitable treatment regimens for each individual patient,” concluded Dr. Shimony.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.