Gender and Obesity Do Not Impact Survival in Diffuse Large B-Cell Lymphoma: Justification for Full Weight-Based Chemotherapy Dosing in All Patients

Background:  The addition of rituximab to CHOP chemotherapy has greatly improved outcomes in diffuse large B-cell lymphoma (DLBCL). However, subgroup analyses from prospective trials have introduced the question of differential benefit of rituximab in older females, due to slower drug clearance (MŸller C1 et al. Blood. 2012; 119(14):3276-84; Zeynalova S, et al. Blood. 2014; 123(5):640-6.) A related question has been the interplay of gender and obesity on outcomes in DLBCL.

Methods: We evaluated the impact of gender and obesity on overall and progression-free survival and treatment toxicity in DLBCL. We further studied the impact of weight loss over the chemotherapy course on outcomes. A comprehensive clinical database of 490 patients with a new diagnosis of de novo or transformed DLBCL treated at our center between 2002 and 2013 was used.  All patients received at least one cycle of R-CHOP chemotherapy (median 6).  We defined older age as greater then 60 and obesity as BMI >25. Chemotherapy toxicity was defined as any admission for febrile neutropenia or other serious infection.

Results: In the population studied (n=490), the median age was 64, with 60% over age 60, and 49.4% were female. There were 51% of patients with BMI >25. All patients received full weight-based chemotherapy dosing, except for universal vincristine dose capping at 2 mg. A total of 173 admissions for febrile neutropenia or other serious infection were identified. Median overall survival and progression-free survival follow up times were 39 and 38 months respectively. The two groups: obese and non-obese, were well balanced with respect to age, gender, ECOG, B-symptoms, and R-IPI. On Cox multivariable regression analysis, only R-IPI (HR=16; p<0.001), Charlson comorbidity index (HR=4.7; p=0.029) and presence of B-symptoms (HR=6.5; p=0.011) impacted overall survival.  In the analysis for progression-free survival, only R-IPI (HR 7.7, p=0.005) and weight loss of > 10% over the full treatment course (HR =4.6; p=0.33) were prognostic. In the logistic regression analysis of chemotherapy toxicity, only ECOG performance status was predictive for infectious complications (OR=6; p=0.14).

Conclusions: In this large retrospective cohort of patients with DLBCL, we could not find an association between gender – in either younger or older subgroups – and lymphoma survival. Weight loss during treatment represented an important prognostic marker of long-term outcome. However, patients who were obese at baseline and received full weight-based chemotherapy dosing did not experience increased toxicity or worse long-term outcomes. These represent the first available data in lymphoma to support recent broad recommendations to forgo chemotherapy dose capping in obese patients.