Renoir phase III Rituximab-Lenalidomide vs Rituximab as Maintenance Treatment in Relapsed/Refractory Follicular Lymphoma
Barbara Botto, Carola Boccomini, Andrea Evangelista, Vittorio Ruggero Zilioli, Antonella Anastasia, Federica Cavallo, Francesco Merli, Manuela Zanni, Monica Tani, Annalisa Chiarenza, Anna Marina Liberati, Annarita Conconi, Chiara Rusconi, Alessia Bari, Ilaria Del Giudice, Gianluca Gaidano, Michele Spina, Nilla Maschio, Claudia Castellino, Delia Rota-Scalabrini, Benedetta Puccini, Annalisa Arcari, Sara Bigliardi, Giorgia Maria Elena Matta, Benedetta Bianchi, Donato Mannina, Dario Marino, Piero Galieni, Fabrizio Ciambelli, Gerardo Musuraca, Cristina Muzi, Chiara Bottelli, Elisa Genuardi, Erika Meli, Simone Ferrero, Stefano Luminari, Marco Ladetto, Giovannino Ciccone, Umberto VitoloMaintenance treatment in elderly patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase III, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in elderly patients with R/R FL after one or two prior therapies. Patients achieving partial or complete response (PR/CR) after 4-6 cycles of standard rituximab-based chemotherapy were randomized 1:1 to maintenance with rituximab alone (R, standard arm) or rituximab plus lenalidomide (R2, experimental arm). The primary endpoint was 2-year progression-free survival (PFS) from randomization with an expected HR =0.5. A total of 152 patients (median age 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR 58%) and were randomized to R (n=65) or R2 (n=64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm (HR 0.73, 95% CI 0.46-1.16, p=.183). An unplanned hypothesis- generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70y (HR=0.35): R2 96% vs R 69%. Two-year overall survival (OS) rates were similar (R2 80% vs R 89%; HR 1.12). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary endpoint of the study was not met and R2 maintenance did not significantly improve 2-year PFS in elderly patients with R/R FL, though a numerically benefit was observed. R2 showed a more favorable benefit/risk profile in patients <70 years whereas in older patients careful consideration of individual tolerability is warranted. Trial registration: RENOIR study (NCT02390869) clinicaltrial.gov