Rituximab Maintenance Prolongs Response Duration after Salvage Therapy with R-FCM in Patients with Relapsed Follicular Lymphomas and Mantle Cell Lymphomas: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).

Preceding studies have shown that Rituximab prolongs the time to treatment failure (TTF) and response duration (RD) in follicular lymphoma (FL) when given either together with chemotherapy or as maintenance after a no R containing therapy. In the current study the impact of R maintenance on RD was evaluated after remission induction by an R-chemo combination. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized a first randomization between 4 courses of chemotherapy with Fludarabine (25mg/m²/d days 1–3), Cyclophosphamide (200mg/m²/d days 1–3) and Mitoxantrone (8mg/m²/d day 1) (FCM) versus FCM plus Rituximab (375mg/m²/d on day 0) (R-FCM). Patients entering a complete (CR) or partial remission (PR) underwent a second randomzation for observation only versus R maintenance with 4 weekly doses of R (375mg/m²/d) to be given at three and nine month after end of therapy. Both randomizations were stratified for histology and preceding therapy. The first randomization was stopped after 147 patients demonstrating a significant improvement for the R-FCM therapy in initial response, progression free survival and even overall survival (OS). So all subsequent patients received R-FCM.

174 cases are currently evaluable for the second randomization, 136 of whom had received R-FCM for remission induction. In these patients the median RD has not been reached in the R-maintenance arm whereas it is 17 months in patients with no further treatment after R-FCM (p=0.0024). This improvement was seen both in FL and MCL. This study demonstrates that R maintenance after R-FCM salvage therapy is highly effective and improves the outcome of patients with relapsed FL and MCL.