Increased Risk of Infectious Complications in Older Patients With Indolent Non-Hodgkin Lymphoma Exposed to Bendamustine

Background Bendamustine is a potent chemotherapy agent increasingly used to treat indolent non-Hodgkin lymphoma (iNHL). While effective, it causes significant T-cell lymphopenia, which may increase risk of infection. We examined infectious complications associated with bendamustine-containing regimens among older patients with iNHL. Methods For this Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study, we identified 9395 patients with iNHL (follicular, marginal zone, Waldenstrom macroglobulinemia) treated with chemotherapy from 2006 to 2013. Thirteen percent received bendamustine-containing regimens. We compared baseline characteristics and infection incidence rates between patients treated with and without bendamustine. We conducted multivariate Cox proportional hazards regression (adjusting for demographics, comorbidities, disease and treatment characteristics, risk factors for infection, and antimicrobial prophylaxis) to determine infectious risks associated with bendamustine. Results Bendamustine was associated with an increased risk of both common infections such as bacterial pneumonia (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85]) and opportunistic infections such as cytomegalovirus (HR, 3.98 [95% CI, 1.40-11.26]), varicella zoster virus (HR, 1.49 [95% CI, 1.18-1.89]), histoplasmosis (HR, 3.55 [95% CI, 1.10-11.42]), and Pneumocystis jirovecii pneumonia (when administered as third-line therapy: HR, 3.32 [95% CI, 1.00-11.11]). Risk of infections was more prominent in patients receiving bendamustine as part of later (third-line and above) regimens, and independently associated with well-established factors such as neutropenia and corticosteroid exposure. Conclusions Bendamustine is associated with an increased risk of common and opportunistic infections in patients with iNHL. Further prospective investigation into the potential role of antimicrobial prophylaxis is needed in these patients.