Phase III RENOIR trial: Rituximab + lenalidomide maintenance vs rituximab alone in R/R

The multicenter, open-label, randomized, phase III RENOIR trial (NCT02390869) evaluated rituximab + lenalidomide (R2) vs rituximab alone (R) as maintenance therapy in patients with relapsed/refractory (R/R) follicular lymphoma (FL) who were elderly (> 65 years) or ineligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) and had received 1 or 2 prior therapies containing rituximab. Following an induction of rituximab-based chemoimmunotherapy, patients were stratified as complete (CR) or partial response (PR) and randomized 1:1 to R2 (n = 64) or R (n = 65). The primary endpoint was 2-year progression-free survival (PFS). Results were published in Blood Advances by Botto et al.

Key data: At a median follow-up of 68 months, 2-year PFS was 73% in the R2 group vs 64% in the R group (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.46–1.16; p = 0.183) and 2-year overall survival (OS) was 80% vs 89%, respectively (HR, 1.12; 95% CI, 0.61–2.03; p = 0.72). In an unplanned exploratory subgroup analysis, patients aged <70 years had a higher 2-year PFS (96% vs 69%) and OS (100% vs 91%) with R2 vs R, respectively. Grade 3/4 treatment-emergent adverse events (TEAEs) were more frequent in the R2 group. Grade ≥3 neutropenia (p < 0.001) and gastrointestinal disorders (p = 0.032) were significantly higher with R2 vs R, while febrile neutropenia (p = 0.262), and infections (p = 0.480) were numerically higher; all other Grade 3/4 TEAEs were comparable. Fatal Grade 5 TEAEs occurred in five patients in the R group and four patients in the R2 group.

Key learning: R2 maintenance did not improve 2-year PFS vs R in patients with R/R FL who were elderly or ineligible for HDC-ASCT. A greater numerical PFS and OS benefit was observed in patients aged <70 years; however, further investigation is required to determine whether age modifies the benefit-risk profile of R2 maintenance.