Bendamustine‐rituximab compared to rituximab‐chop/cvp for treatment of patients with indolent lymphoma in ontario: a population‐based study

Introduction: For patients with symptomatic advanced stage indolent lymphoma, rituximab (R) was traditionally used alongside cyclophosphamide, vincristine, prednisone (CVP), or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Bendamustine plus rituximab (BR) has been found to increase progression-free survival compared to R-CHOP/CVP, although controversy exists around its toxicity profile. Since 2013, bendamustine has been approved for universal public reimbursement for this indication in Ontario, Canada, and become the preferred regimen. We examined survival and toxicity of patients with indolent lymphoma treated with BR compared with RCVP/CHOP in Ontario. Methods: We conducted a retrospective cohort population-based study using administrative healthcare databases from Ontario, Canada. Patients with a diagnosis of indolent lymphoma, excluding mantle cell lymphoma, who were treated with R-CVP/CHOP from 2005 to 2012 or with BR from 2013-2018 were included. The two treatment groups were propensity score matched based on lymphoma subtype, age, sex, prior cancer diagnosis, time since diagnosis and rural/urban residence. The primary outcome of the study is overall survival (OS) from time of first treatment to date of death or end of study period. Secondary outcomes include toxicities, such as infections and secondary malignancies, associated resource use, and outcomes of patients treated with rituximab maintenance therapy. Results: A propensity-matched cohort of 2029 patients treated with BR and 2029 patients treated with R-CVP/CHOP were included. The median age of patients was 64 years and 48% were female in the cohort. A majority of patients had a diagnosis of follicular lymphoma (59.3% of patients treated with BR, 59.7% of patients treated with R-CVP/CHOP, p = 0.88). Median follow-up time was 41 and 87 months for patients treated with BR and R-CVP/CHOP, respectively. In this well-matched cohort, BR was associated with a significant improvement in survival compared to R-CVP/CHOP (HR 0.76, 95% CI 0.67-0.88, p < 0.01). Five-year OS was 80% and 75% for patients treated with BR and R-CVP/CHOP, respectively (Figure 1). A total of 974 patients died during the follow-up period (331 treated with BR, 643 treated with R-CVP/CHOP), of which 875 had causes of death available. A majority of patients in both groups died from lymphoma (63.2% treated with BR, 66.4% treated with R-CVP/CHOP). Death from secondary malignancies was less common (11.8% treated with BR, 12.8% treated with R-CVP/CHOP). Few patients died from infection (6.2% treated with BR, 3.2% treated with R-CVP/CHOP). Conclusions: Our study demonstrates improved OS with BR compared to R-CVP/CHOP for patients with previously untreated indolent lymphoma. Cause of death in both cohorts was most frequently attributable to lymphoma. This supports BR as the standard of care for treatment of symptomatic indolent lymphoma. Kaplan-Meier plot of overall survival of the treatment groups from time of treatment initiation The research was funded by: This project was in part supported by the American Society of Hematology HONORS (Hematology Opportunities for the Next Generation of Research Scientists) Award granted to Adam Suleman. Keywords: Indolent non-Hodgkin lymphoma, Combination Therapies No conflicts of interest pertinent to the abstract.