Background
Phase 3 RENOIR (Fondazione Italiana Linfomi), multicenter, open-label. Elderly R/R follicular lymphoma after 1–2 prior therapies; 152 enrolled (median age 71), 129 responders (ORR 85%, CR 58%) to 4–6 cycles of rituximab-chemo induction randomized 1:1 to maintenance.
Results
Interventions and follow up: Arm A: rituximab + lenalidomide (R2) maintenance (n=64)
Arm B: rituximab maintenance (n=65, standard)
Primary endpoint: 2-yr PFS from randomization (designed for HR 0.5)
mFollow up: 68 mo
Results: 2-yr PFS: 73% (R2) vs 64% (R); HR 0.73 (95% CI 0.46–1.16), P=.183 — primary endpoint NOT met
2-yr OS: 80% vs 89%; HR 1.12
Subgroup age <70 (unplanned): 2-yr PFS 96% vs 69%; HR 0.35 — hypothesis-generating only
Arm B: rituximab maintenance (n=65, standard)
Primary endpoint: 2-yr PFS from randomization (designed for HR 0.5)
mFollow up: 68 mo
Results: 2-yr PFS: 73% (R2) vs 64% (R); HR 0.73 (95% CI 0.46–1.16), P=.183 — primary endpoint NOT met
2-yr OS: 80% vs 89%; HR 1.12
Subgroup age <70 (unplanned): 2-yr PFS 96% vs 69%; HR 0.35 — hypothesis-generating only
Adverse events
Grade 3/4 (any): more frequent with R2 (rates NR)
Most common with R2: neutropenia, gastrointestinal disorders
Most common with R2: neutropenia, gastrointestinal disorders
Conclusions
Adding lenalidomide to rituximab maintenance did not significantly improve 2-yr PFS in elderly R/R FL despite a numerical benefit, with added toxicity. In older patients, individual tolerability should drive maintenance choice; the <70 signal warrants prospective study.
Key Limitations
Underpowered — design assumed an optimistic HR of 0.5; observed HR 0.73 could not reach significance with 129 randomized. Open-label. Age-subgroup benefit was unplanned/exploratory. Elderly-only population limits applicability of the <70 finding.
Clinical Context
R2 is FDA-approved as treatment for R/R FL (AUGMENT), but RENOIR does not support extending lenalidomide into the maintenance phase after rituximab-chemo salvage in elderly patients. Rituximab maintenance remains the standard maintenance option in this setting.