Survival Disparities Among Overweight and Obese Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia in a Large Integrated Healthcare System

Introduction:

Acute leukemias are highly prevalent diagnoses among adolescent and young adult (AYA) patients and are a leading cause of mortality in this age group despite promising therapeutic advancements. Obesity, often measured in surrogate by body mass index (BMI), is an increasingly common condition in the United States, including in AYAs, and is associated with inferior survival outcomes across many cancer types. Recent work has shown that AYAs undergoing treatment for B- or T-acute lymphoblastic leukemia (B-ALL, T-ALL) are adversely impacted by obesity as well, both in terms of treatment-related toxicities and overall survival (OS). Thus far, this relationship has been examined in the context of clinical trials with limited ethnic inclusion. Data detailing outcomes for racially and socioeconomically diverse AYA patients treated in the community setting are sparse. Herein, we describe the impact of obesity on survival outcomes in a diverse set of AYAs being treated for ALL within a large integrated healthcare system.

Methods:

Patient data were derived from the Kaiser Permanente Southern California (KPSC) membership, where patients are diagnosed, treated, and followed within a single integrated healthcare system. KPSC members have relatively equal access to care. 140 AYA patients aged 15-39 diagnosed with B- or T-ALL were identified via ICD-O-3 histology codes from 2010-2018. Descriptors of age, race/ethnicity, census-level median household income, and BMI within one year prior to diagnosis were abstracted from KPSC’s electronic health records. BMI was categorized by World Health Organization (WHO) definitions. Comorbidities were captured using a modified Elixhauser comorbidity index (ECI) excluding obesity and cancer-related conditions. The Kaplan-Meier method was used to construct survival curves for OS, alongside Log-rank testing of survival equivalence. Bivariate and multivariable Cox proportional hazards (PH) modeling was employed to determine hazard ratios (HRs) and confidence intervals (CIs).

Results:

The 140 included patients were ethnically diverse, with nearly 80% identifying with a background other than non-Hispanic white. Half (51%) were from lower socioeconomic brackets as measured by census-level income. One third (31%) were a normal weight (BMI 18.5-24.9), with the other two thirds (59%) presenting as overweight (BMI 25-29.9), obese (BMI 30-39.9), or severely obese (BMI ≥ 40) at the time of diagnosis. Most were diagnosed with B-ALL (76%) compared to T-ALL (21%), and a minority presented with mixed lineage leukemia (3%). Log-rank testing of survival functions yielded poorer outcomes for overweight and obese AYAs relative to normal weight peers, both as a composite group (p=0.01) and by graded WHO BMI category (p=8e-5), with a dose-dependent relationship of increased BMI and inferior survival observed. Inferior survival was also associated with lower income brackets (p=0.002), but no significant differences were found between race/ethnic groups (p=0.1). Multivariable Cox PH modeling correcting for sex, race/ethnicity, income, and ECI showed that composite overweight/obese BMI was associated with inferior survival relative to normal weight peers (HR 2.62, 95% CI 1.14 - 6.01). AYAs identifying as African American and Hispanic also had poorer outcomes compared to non-Hispanic white patients (HR 7.29, 95% CI 1.43 - 37.34 and HR 3.31, 95% CI 1.04 - 10.58). Repeat multivariable testing sub-grouped by BMI category showed significant dose-dependent associations of inferior survival in obese (HR 2.68, 95% CI 1.02 - 7.08) and severely obese (HR 5.39, 95% CI 2.01 - 14.44) patients relative to normal BMI. Overweight BMI trended similarly but did not reach significance (HR 1.69, 95% CI 0.65 – 4.39).

Conclusions:

Among racially and socioeconomically diverse AYAs receiving treatment for ALL in the community setting with equal access to care, inferior survival outcomes were still found in overweight and obese patients. Further longitudinal studies are needed to better delineate contributions of overweight/obese BMI to durability of treatment response and therapeutic toxicities in this population. However, these findings add to our understanding of the impact of obesity on survival outcomes in AYA patients with ALL in the real-world setting, and to continued discussion of therapeutic considerations in the context of the evolving treatment landscape for patients.