Obesity Associated With Worse Outcomes in Adolescent/Young Adults Treated for ALL

Adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) who are overweight or obese and are treated with asparaginase-containing pediatric regimens, are likelier to have poorer outcomes than those with normal body mass index (BMI), researchers have found.

Among 388 AYA patients, being overweight or obese was associated with higher non-relapse mortality ([NRM] 11.7% vs 2.8%, P=0.006), worse event-free survival (4-year [EFS], 63% vs 77%, P=0.003), and worse overall survival (4-year [OS], 64% vs 83%, P=0.0001), reported Marlise R. Luskin, MD, MSCE, of the Dana-Farber Cancer Institute in Boston, and colleagues in Blood Advances.

Moreover, the harmful effect of elevated BMI was more pronounced in older AYAs.

For example, while 4-year OS rates were high among both younger (15-29 years) and older (30-50 years) AYAs with normal BMI (83% vs 85%, P=0.89), they were substantially worse in older AYAs who were overweight/obese compared with younger AYAs (55% vs 73%, P=0.023).

The same held true for EFS, with similar 4-year EFS rates between younger and older AYAs with normal BMI (78% vs 74%, P=0.63), while 4-year EFS was higher in younger vs. older AYAs who were overweight/obese (71% vs 55%, P=0.11), with an EFS rate that was particularly poor among obese older AYAs (49%).

“Overall, our findings emphasize that clinicians and clinical investigators should consider both age and BMI in making treatment decisions,” wrote Luskin and colleagues. “Future trials of ALL treatments among patients of all ages should study the impact of obesity on treatment toxicity and outcomes.”

The 4-year cumulative incidence of relapse (CIR) was not statistically different between normal and overweight/obese BMI (18.2% vs 23.4%, P=0.18). While the 4-year CIR was similar between younger and older AYAs (17.9% vs 18.8%, P=0.89) in the normal BMI group, among patients with overweight/obese BMI, it was numerically lower in younger patients than older patients (17.1% vs 30.1%, P=0.13).

NRM was similar between younger and older AYAs in the normal BMI group (2.1% vs 5.2%, P=0.46), as well as overweight/obese BMI group (10.1% vs 13.4%, P=0.46).

Of the 388 patients in the study, most were male (61.9%) and the median age was 24 years, with 65% in the younger group and 35% in the older group. BMI at diagnosis was underweight for 2.6% of patients, normal for 50.7%, overweight for 25%, and obese for 21.7%.

All treatment protocols included an induction phase, a consolidation phase that included 30 weeks of continuous asparaginase depletion, and a continuation phase which continued until 2 years from achievement of complete remission. Older protocols used native E. coli asparaginase preparation, while newer protocols incorporated PEG-asparaginase.

“As obesity is a serious disease with increasing rates in the last 20 years, the challenge of treating overweight and obese patients with ALL will be more common, and the optimal therapy, especially for older obese patients has yet to be defined,” Luskin and colleagues observed. “Given that AYAs with obesity fare more poorly with asparaginase-based pediatric regimens as compared to AYAs with normal BMI, alternative approaches including but not limited to alternative asparaginase dose and schedules should be explored.”

Regarding toxicity, Luskin and colleagues observed that AYAs with overweight/obese BMI experienced higher rates of grade III/IV hepatotoxicity and hyperglycemia (60.7% vs 42.2%, P=0.0005, and 36.4% vs. 24.4%, P=0.014, respectively), but had comparable rates of hypertriglyceridemia (29.5% vs 24.4%, P=0.29).

The authors also conducted an exploratory analysis comparing OS, EFS, CIR and NRM between patients with and without grade III/IV hypertriglyceridemia or hyperglycemia and determined that grade III/IV hypertriglyceridemia was associated with lower cumulative relapse rates and improved EFS and OS, demonstrating “for the first time hypertriglyceridemia is associated with improved survival and decreased risk of relapse, most likely reflecting asparaginase activity and thus should not be viewed as an adverse event.”