Bendamustine-Rituximab versus Rituximab Monotherapy for Older Patients with Nodal or Splenic Marginal Zone Lymphoma

Conference Correspondent - ASH 2019 Wrap-up


Nodal marginal zone lymphoma (NMZL) and splenic marginal zone lymphoma (SMZL) are increasingly treated with first-line bendamustine-rituximab (BR) based on phase 3 trial results from various indolent B-cell lymphomas. Given the unique biology and clinical course of NMZL/SMZL, the efficacy and safety of BR compared with single-agent rituximab, specifically in SMZL/NMZL, must be determined. Using population-based databases, the current study was undertaken to determine treatment patterns, and compare survival and safety outcomes of BR versus rituximab in NMZL and SMZL.

The Surveillance, Epidemiology, and End Results Medicare claims database linked to cancer registry data was used to identify all SMZL/NMZL patients aged ≥65 years who received first-line BR or rituximab between 2009 and 2016. A propensity score was used to generate “pseudo-randomized” cohorts (pooled, including NMZL and SMZL, and histology-specific for NMZL and SMZL) that were well-balanced for patient and disease characteristics (age, sex, race, comorbidities, performance status, lymphoma stage, B symptoms, prior splenectomy, anemia, transfusions, hospitalizations, and time from diagnosis to therapy). In the balanced pseudo-randomized cohorts, event-free survival (EFS; defined as second-line chemotherapy, splenectomy, hospice, or death) and overall survival (OS) from the start of therapy, risk for major toxicities (hospitalization, transfusions), and inflation-adjusted Medicare spending were compared.

The balanced, pseudo-randomized cohorts included 1315 patients. The analytical cohort was 926 patients in the NMZL/SMZL cohort that received BR or rituximab (NMZL, 609; SMZL, 317). Whereas about half of patients received first-line rituximab every year between 2009 and 2016, the use of BR increased from 4% (2009) to 23% (2016). Among the NMZL/SMZL cohort of patients receiving BR or rituximab, patients who received BR were younger and were more likely to have NMZL, stage 2 to 4 lymphoma, and B symptoms. With median follow-up of 3.8 years, median EFS was 4.3 years (95% confidence interval [CI], 3.5-5.1) and median OS was 5.7 years (95% CI, 4.9-6.7) in the NMZL cohort, and 4.5 years (95% CI, 3.8-6.5) and 5.2 years (95% CI, 4.4-6.7), respectively, in the SMZL cohort. Overall, there was no significant difference in either EFS (hazard ratio [HR] for BR, 1.00; 95% CI, 0.76-1.30; P = .98) or OS (HR, 1.14; 95% CI, 0.85-1.53; P = .38). Toxicities were greater with BR, including hospitalizations (risk ratio [RR], 1.46; 95% CI, 1.14-1.87; P = .003) and transfusions (RR, 2.35; 95% CI, 1.55-3.56; P <.001). Mean Medicare spending within 1 year of diagnosis was higher after BR (mean, $83,480) than after rituximab (mean, $53,776; P <.001).

Separate propensity score models were fitted for the NMZL and SMZL cohorts. In the NMZL cohort (N = 609), 434 patients (71%) received rituximab, and 175 patients (29%) received BR. No significant differences were observed in EFS (HR for BR, 0.93; 95% CI, 0.68-1.29; P = .67) or OS (HR, 1.16; 95% CI, 0.82-1.63; P = .40); however, toxicities and costs were consistently higher with BR. In the SMZL cohort (N = 317), 272 patients (86%) received rituximab, and 45 patients (14%) received BR. Similar to the NMZL cohort, there were no significant differences in EFS (HR for BR, 0.84; 95% CI, 0.46-1.53; P = .56) or OS (HR, 0.92; 95% CI, 0.46-1.83; P = .80), but toxicities and costs were higher.

Based on this large observational study, it was concluded that the use of first-line BR is increasing among older patients with SMZL and NMZL treated in the community. However, BR was not associated with any significant EFS or OS benefit over single-agent rituximab, but was associated with increased toxicities and costs.

Olszewski AJ, et al. ASH Abstract 2824. Session 623.