IBCL-081 MAGNIFY Phase 3b Study of Lenalidomide + Rituximab (R2) Followed by Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Complete Induction Phase Analysis

Context: Patients with relapsed indolent NHL (iNHL) have limited standard treatment options. Lenalidomide + rituximab (R²) has shown complimentary clinical activity and is tolerable in both untreated and relapsed/refractory (R/R) iNHL. Design: MAGNIFY is a multicenter, phase 3b trial in R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL; NCT01996865). In the induction phase, lenalidomide 20mg PO d1–21 of a 28-d cycle + rituximab IV 375mg/m²/week cycle 1 and then q8w starting with cycle 3 (R²) are administered for 12 cycles. Patients with ≥SD were randomized 1:1 to R² vs rituximab maintenance for 18 months. Data here are the complete induction phase analysis in efficacy-evaluable patients with FL grades 1–3a or MZL. The focus of this interim analysis was ORR by 1999 IWG criteria in the induction ITT population. Results: As of March 5th, 2021, 394 patients (318 [81%] FL gr1–3a; 76 [19%] MZL) were enrolled. Median follow-up was 40.6 mo (range, 0.6–79.6). Median age was 66 y (range, 35–91), 328 (83%) had stage III/IV disease, with a median of 2 prior therapies (94% prior rituximab-containing). ORR was 71% with 42% CR/CRu. All patients have completed R² induction (n=232, 59%) or discontinued study treatment (n=162, 41%); 141 patients (36%) prematurely discontinued both lenalidomide and rituximab, primarily due to AEs (n=54, 14%) or PD (n=42, 11%). The majority who have completed induction have been randomized and entered maintenance (n=217). Median DOR in the induction period was NR (95% CI, 43.9 mo–NR); median PFS in the induction safety population was 50.5 mo (95% CI, 39.5–NR). Most common all-grade TEAEs were 47% fatigue, 43% neutropenia, 37% diarrhea. Grade 3/4 AEs occurring in ≥5% of patients included 37% neutropenia (10 patients [3%] had febrile neutropenia), 8% leukopenia, 6% thrombocytopenia, 5% anemia, 5% fatigue. Conclusions: These data represent a complete analysis of all patients in the induction phase of MAGNIFY that continue to support that R2 is active with a tolerable safety profile in patients with R/R FL grade 1–3a and MZL, including rituximab-refractory, double-refractory, and early relapse patients.