Renoir phase III Rituximab-Lenalidomide vs Rituximab as Maintenance Treatment in Relapsed/Refractory Follicular...

Maintenance 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.