Underweight Body Mass Index Is an Independent Risk Factor for Overall Survival in Diffuse Large B-Cell Lymphoma Treated with Rituximab, Prednisolone, Cyclophosphamide, Vincristine, and Doxorubicin: A Lymphoma and Related Diseases Registry Study
Authors: Yao Yao , Sungur Serif , Wellard Cameron , Chung Eliza , Morgan Susan , Lee Denise , Chong Geoffrey , Cheah Chan Y. , Hawkes Eliza A. , Wood Erica M. , Hamad Nada , Johnston Anna M. , Armytage Tasman 
Published: December 2024

Introduction
In patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, prednisolone, cyclophosphamide, vincristine, and doxorubicin (RCHOP) diverse body sizes may influence treatment outcomes. Underweight, according to body mass index (BMI), has been associated with inferior survival, whereas the prognostic implications of being overweight or obese as well as chemotherapy dosing in these individuals are unclear.1,2 Weight bias and stigma are widespread in health care and may prevent individuals from receiving adequate care, leading to discrimination and negative health outcomes.3 This study explored the association between BMI, chemotherapy delivery, and lymphoma survival in a prospective registry.
Methods
Adult DLBCL patients recruited to the Lymphoma and Related Diseases Registry (LaRDR) between 5 Jan 2016 and 1 November 2023 and treated with RCHOP were included. BMI was categorized into five groups: underweight (&lt; 18.5 kg/m2), normal weight (18.5 - 24.9 kg/m2), overweight (25 - 29.9 kg/m2), obese class I (30 - 34.9 kg/m2), and obese class II or III (≥ 35 kg/m2). Other prognostic factors included age, sex, lymphoma characteristics, biochemical markers, prescribed chemotherapy dose, and chemotherapy received. The primary endpoints were overall survival (OS); time from diagnosis to death, and progression-free survival (PFS); time from diagnosis to disease progression or death from any cause. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazard regression by complete case analysis. Ethics was approved by the Monash Health Human Research Ethics Committee (HREC/16/MonH/74).
Results
1105 participants were eligible and formed five BMI groups: 371 (34%) normal weight, 31 (3%) underweight, 379 (34%) overweight, 192 (17%) obese class I, 132 (12%) obese class II or III. Forty-eight patients (5%) had upfront chemotherapy dose reduction. There was no association between BMI groups and frequency of upfront chemotherapy dose reduction (5% normal weight, 6% underweight, 4% overweight, 4% obese class I, 4% obese class II or III, P = 0.8).
Median follow-up was 27 months (range 0-87 months), during which 242 (22%) deaths occurred. Median OS was significantly shorter for underweight group, while there was no difference for overweight and obese groups, compared to normal weight controls. Median OS for underweight group was 34 months vs. not reached for any other BMI groups (P = 0.005). 195 (18%) patients had documented disease progression. There was no statistically significant difference in PFS between BMI groups. Median PFS for the underweight group was 26 months vs. not reached for any other BMI groups (P = 0.07).
The underweight group was associated with inferior OS (underweight adjusted hazard ratio [adj. HR] 3.8, 95% confidence interval [CI] 1.9-7.3, obesity class I adj. HR 1.1, CI 0.7-1.8; obesity class II or III adj. HR 0.7, CI 0.4-1.5; overall P = 0.007) while adjusting for age, sex, history of cardiac disease, Eastern Cooperative Oncology Group Performance Status, lactate dehydrogenase level, Ann Arbor stage, individual extranodal sites involved (liver, central nervous system, and bone or bone marrow), upfront chemotherapy dose reduction, body surface area, and incomplete chemotherapy. There was no significant association between BMI groups and PFS (underweight adj. HR 2.1, CI 1.1-4.1; obese class I adj. HR 1.4, CI 0.9-2.1; obese class II or III adj. HR 0.8, CI 0.4-1.5; overall P = 0.07) after adjusting for the same co-factors as the OS analysis, as described above.
Conclusion
Underweight DLBCL patients receiving RCHOP had inferior OS, while obese patients showed no survival difference compared to normal weight controls. Upfront chemotherapy dose reduction was uncommon and not associated with body size. Avoiding weight stigma is essential, and this study supports full weight-based dosing for RCHOP in obese DLBCL patients. Further research is needed to understand why underweight patients have poor survival.
References
1. Wang Z et al. The Prognostic Impact of Body Mass Index in Patients with Diffuse Large B-Cell Lymphoma: A Meta-Analysis. Nutr Cancer. 2021;73:2336-46.
2. Griggs JJ et al. Appropriate Systemic Therapy Dosing for Obese Adult Patients With Cancer: ASCO Guideline Update. J Clin Oncol. 2021;39:2037-48.
3. Rubino F et al. Joint international consensus statement for ending stigma of obesity. Nat Med. 2020;26:485-97.