Addition of Rituximab to First-Line MCP (Mitoxantrone, Chlorambucil, Prednisolone) Chemotherapy Prolongs Survival in Advanced Follicular Lymphoma - 4 Year Follow-Up Results of a Phase III Trial of the East German Study Group Hematology and Oncology (OSHO#39).

Abstract

Introduction: Rituximab plus chemotherapy has been proved to be the gold - standard in treating advanced follicular lymphoma. Here we report the 4-year-follow-up data of our phase III trial comparing MCP - chemotherapy vs rituximab + MCP both followed by interferon maintenance in advanced symptomatic follicular lymphoma. Methods: Previously untreated patients with advanced stage (III + IV) symptomatic CD 20-positive indolent NHL and mantle cell lymphoma (n=358) were randomized to receive either MCP-chemotherapy (mitoxantrone 8 mg/m² d1+2, chlorambucil 3x3 mg/m² d 1–5, prednisolone 25 mg/m² d 1–5 x 8 q 4 weeks) or MCP + rituximab (375 mg/m² d −1). Here we report the results of the ITT population of patients with follicular lymphoma (FL) (grade 1+2), who represented the majority of patients and for whom the sample size primarily was calculated, so this is not a subgroup analysis. Study endpoints included overall and complete response rate (RR + CR), progression free survival (PFS), event free survival (EFS), time to next treatment (TTNT), overall survival (OS) and toxicities. Results: with a median follow - up of nearly 4 years (47 months) we are able to provide relatively mature data. Concerning toxicities there was no striking difference, but there was a significantly increased risk to experience a CTC grade III or IV toxicity for leukocytes in the R-MCP arm, however this did not increase the risk of infections. For the FL - ITT population the results are given in the table. Conclusions: Concerning all end points rituximab plus MCP is significantly superior to MCP alone in the treatment of advanced follicular lymphoma. Special attention should be drawn to the fact, that after a median follow-up of 47 months we can demonstrate a clinically and statistically significant survival advantage for the immunochemotherapy. Results R-MCP (n=105) MCP (n=96) p-value Response rate 92,4% 75% .0004 Complete Response 49,5% 25% .0009 PFS median n.r. 29 months < .0001 PSF 4 years 71% 40% EFS median n.r. 26 months < .0001 EFS 4 years 69% 35,5% TTNT median n.r. 29,4 months .0002 OS median n.r. n.r. .0096 OS 4 years 87% 74%