Treatment-Related Weight Change and Overall Survival in United States Veterans with Follicular Lymphoma
Authors: Xiao Daphne Y , O'Brian Katiuscia , Luo Suhong , Carson Kenneth R 
Published: October 2019

Abstract
Introduction
Weight loss during chemotherapy has been associated with decreased overall survival (OS) in various solid tumors. While weight loss >10% in the 6 months leading up to diagnosis is a known adverse prognostic factor for non-Hodgkin's lymphoma (one of the B symptoms), the association between weight loss during chemotherapy and survival in follicular lymphoma (FL) patients is not well understood. Few studies have looked at long-term weight change patterns following chemotherapy treatment in this patient population. We investigated short and long-term weight change trends, predictors, and association with OS and disease-specific survival (DSS) in a cohort of FL patients.
Methods
FL patients diagnosed and treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) +/- rituximab, CVP (cyclophosphamide, vincristine, and prednisone) +/- rituximab, or rituximab monotherapy regimens between 1998 and 2010 were identified in the Veterans Health Administration database. Data on weight 1 year prior to treatment, at time of first treatment (baseline), and up to 5 years after treatment initiation was obtained. Additional data on height, age, stage, race, comorbidities, date of diagnosis, LDH, and B-symptoms was obtained. Body Mass Index (BMI) at diagnosis was categorized according to World Health Organization criteria. Weight change during treatment is calculated as difference between baseline weight and 3 months after start of treatment. Long-term weight change is calculated as difference between baseline weight and 24 months after start of treatment. Logistic regression identified factors associated with long-term weight gain. Landmark Cox analysis evaluated prognostic significance of weight loss during treatment among patients who survived at least 6 months after treatment initiation.
Results
1022 patients met inclusion criteria out of 2235. Mean and median age at diagnosis was 63.6 and 63.0 years respectively, 95.9% were men, and 72.7% had Stage III/IV disease. The mean Charlson co-morbidity score was 2.3. B symptoms were present in 37.9% and LDH was elevated in 26.8%.
Mean and median weight change during treatment was -1.4kg (-1.5%) and -0.4kg (-0.6%), with a majority of patients losing weight (56%) and 23% of patients losing >5% of their baseline weight. In contrast, mean and median weight change at 24 months after treatment initiation was +1.2kg (+1.6%) and +1.3kg (+1.6%), with a majority of patients (57%) gaining weight and 14% of patients gaining >10% of their baseline weight after treatment completion.
Logistic regression analysis identified factors associated with increased risk of weight gain >10% at 24 months after treatment initiation. These included: weight loss >5% in the year prior to treatment (Odds Ratio (OR) 6.82, 95% Confidence Interval (CI) 3.09-15.05), weight gain between 0-5% during treatment (OR 2.53, 95% CI 1.21-5.27), and weight gain >5% during treatment (OR 9.43, 95% CI 3.85-23.14).
Kaplan-Meier survival analysis showed that weight loss >5% during treatment was associated with decreased OS (p<0.0001) and disease specific survival (DSS) (p=0.0027) compared to weight loss <5% or weight gain. A landmark Cox analysis controlling for age, disease stage, comorbidities, elevated LDH, B symptoms, BMI at diagnosis, and treatment type showed that weight loss >5% during treatment was independently associated with worse OS (Hazard Ratio (HR) 1.71, 95% CI 1.32-2.22) and DSS (HR 1.61, 95% CI 1.11-2.34).
Conclusions
In patients with FL, weight loss >5% during treatment is independently predictive of worse overall survival and disease-specific survival. Weight loss could be considered in conjunction with other dynamic variables (such as PET positivity and nodal size) to assess prognosis at the end of therapy. 14% of patients experience long-term weight gain >10% of baseline. Patients who gained 5% or more during treatment are at highest risk (OR=9.4) for long-term weight gain-this subset of patients could be targeted for weight loss interventions to prevent future obesity-related comorbidities.

Disclosures
No relevant conflicts of interest to declare.