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RITUXIMAB MAINTENANCE VERSUS OBSERVATION AFTER IMMUNOCHEMOTHERAPY (R‐CHOP, R‐MCP, R‐FCM) IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA: A RANDOMISED TRIAL OF GLSG AND OSHO

2017; Wiley; Volume: 35; Issue: S2 Linguagem: Inglês

10.1002/hon.2437_12

1099-1069

Eva Hoster, Michael Unterhalt, Mathias Hänel, Gabriele Prange‐Krex, Roswitha Forstpointner, A. Florschütz, Ullrich Graeven, Norbert Frickhofen, Gerald Wulf, Eva Lengfelder, Christian Lerchenmüller, Rudolf Schlag, Judith Dierlamm, Ludwig Fischer von Weikersthal, Anam Ahmed, Hanns‐Detlev Harich, Andreas Rosenwald, Wolfram Klapper, Martin Dreyling, Wolfgang Hiddemann, Michael Herold,

Chronic Lymphocytic Leukemia Research

Introduction: Despite frequent long lasting remissions to first-line treatment, follicular lymphoma of advanced stages is characterized by recurrent relapses. In the randomized PRIMA trial of the GELA, rituximab maintenance achieved prolonged progression-free survival (PFS) compared with observation in remission after first-line immunochemotherapy (Salles et al., Lancet 2011). The German study groups GLSG and OSHO initiated in 2007 a double randomized trial to investigate the efficacy and safety of rituximab maintenance versus observation in remission after randomly assigned induction treatment. Methods: Previously untreated patients with Ann Arbor stage II-IV follicular lymphoma in need of therapy and not candidates for autologous stem cell transplantation or curative radiotherapy were randomised to receive 6 cycles of R-CHOP, R-MCP, or R-FCM. Patients responding to induction treatment were subsequently randomised to 2 years rituximab maintenance or observation, stratified by type of induction treatment, quality of remission, and FLIPI. The trial was initially planned to detect with 95% power a 15% difference in complete remission rates between any of the three induction groups and a PFS hazard ratio of 0.60 by postremission strategy. Results: Recruitment was stopped in 2011 after the PRIMA results had been published. Median age of the 206 recruited patients was 66 years (range, 24-86), and FLIPI was low in 13%, intermediate in 28%, and high in 60%. A trend towards higher complete remission rates with R-FCM (43% of 58 patients) compared to R-CHOP (23% of 66) and R-MCP (24% of 66) was observed, but the differences were not statistically significant. High and comparable overall response rates were observed after R-CHOP (88%), R-MCP (89%), and R-FCM (91%). In terms of grade 3-4 leukocytopenia and grade 3-4 thrombocytopenia, R-FCM (92%, 17%) was more toxic than R-MCP (88%, 6%) which was more toxic than R-CHOP (63%, 3%); R-CHOP showed more frequent neurological toxicities (40%) compared with R-MCP (14%) and R-FCM (16%). Rituximab maintenance substantially prolonged progression-free survival in comparison to observation in remission (hazard ratio 0.39, p = 0.0064). In the rituximab maintenance group, 3-years PFS was 89% (8 PFS events among 65 patients) compared with 69% in the observation group (19 events among 63 patients). With 11 events, no differences in overall survival could be observed for maintenance vs. observation (hazard ratio 1.04, 95% CI 0.32-3.43, p = 0.95). Rituximab maintenance was more toxic with regards to leukocytes and the gastro-intestinal tract. Conclusions: In this randomized trial, 2 years rituximab maintenance was associated with substantially prolonged PFS in comparison to observation after response to first-line immunochemotherapy in follicular lymphoma. Our data represent an independent confirmation of the GELA PRIMA trial results. Keywords: follicular lymphoma (FL); immunochemotherapy; rituximab.