Bendamustine in Combination with Rituximab As First-Line Treatment of Splenic Marginal Zone Lymphoma (BRISMA). Results of the IELSG-36 Phase II Study

Background and Purpose Splenectomy, as well as immunotherapy with Rituximab, provides a quick palliation in patients with SMZL, despite being unable to achieve cure. Thus systemic chemotherapy is ultimately required in most cases where it has been demonstrated effective although burdened by substantial toxicity. The IELSG-36 phase II study investigated the efficacy and safety of the association of Rituximab with Bendamustine as the first line treatment of non splenectomized SMZL patients.

Patients and Methods The IELSG-36 is an open-label, single arm phase II study designed according to Simon's two-stage method. The primary end point was complete response rate (CRR). Seventy-eight SMZL patients showing active symptomatic disease were registered at 30 centers in Italy and France. In 56 patients (71.8%) the diagnosis was confirmed on central revision and the patients were addressed to treatment with Bendamustine (90 mg/m2 day 1-2) and Rituximab 375 mg/m2 day 1 q28 for six cycles.

Results CRR and Overall Response Rate were 61% and 91%, respectively. With a median observation time of 30 months, 3-yr OS, PFS and DOR were 95% (95CI 81-98), 89% (95CI 75-95) and 93% (95CI 80-98), respectively. The recorded toxicity was mild, mostly hematological, and mainly reported during the first three cycles, although an exception G>3 neutropenia evenly occurred during the whole treatment course.

Conclusions Bendamustine in association with Rituximab is effective and well tolerated as first line immuno-chemotherapy regimen for non splenectomised SMZL. The favorable toxicity profile suggests the choice of this regimen when an association of chemotherapy with Rituximab is deemed to be used for high risk, heavily symptomatic non splenectomized SMZL patients.