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

Introduction:
Patients with relapsed indolent NHL (iNHL) have limited standard treatment options. Lenalidomide combined with rituximab (R ) has shown complimentary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) patients with iNHL (RELEVANCE 2018;379:934 and AUGMENT: . 2019;37:1188).
Methods:
MAGNIFY is a multicenter, phase 3b trial in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL; NCT01996865) exploring optimal lenalidomide duration. In the induction phase, lenalidomide 20 mg PO on days 1–21 of a 28-day cycle + rituximab IV at 375 mg/m /week cycle 1 and then every 8 weeks starting with cycle 3 (R ) are administered for 12 cycles. Patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) were randomized 1:1 to R vs rituximab maintenance for 18 months. Data presented here are the complete analysis from the induction phase in efficacy-evaluable patients with FL grades 1–3a or MZL (FL grade 3b, tFL, and MCL not included). The focus of this interim analysis was overall response rate (ORR) by 1999 IWG criteria in the induction intention-to-treat population.
Results:
As of March 5, 2021, 394 patients (318 [81%] FL gr1–3a; 76 [19%] MZL) were enrolled. The 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% (n=279) with 42% (n=164) CR/CRu. All patients have completed R induction (n=232, 59%) or discontinued study treatment (n=162, 41%). 141 patients (36%) prematurely discontinued both lenalidomide+rituximab, primarily due to adverse events (AEs) (n=54, 14%) or progressive disease (n=42, 11%). The majority of patients who have completed induction have been randomized and entered maintenance (n=217). Median duration of response in the induction period was not reached (95% CI, 43.9 mo–NR), and median progression-free survival in the induction safety population (n=393) was 50.5 mo (95% CI, 39.5–NR). Most common all-grade AEs were 47% fatigue, 43% neutropenia, 37% diarrhea, 30% nausea, and 30% constipation. Grade 3/4 AEs occurring in ≥5% of patients included 37% neutropenia (10 patients [3%] had febrile neutropenia), 8% leukopenia, 6% thrombocytopenia, 5% anemia, and 5% fatigue. TEAEs lead to discontinuation of lenalidomide in 19% of patients and rituximab in 12% of patients; reduction or interruption of lenalidomide in 64% of patients; and to interruption of rituximab in 30% of patients (dose reduction for rituximab was not allowed). Neutropenia was the most common TEAE leading to lenalidomide discontinuation in 6% and reduction/interruption in 32%, and rituximab discontinuation in 3%. Infusion-related reaction was the most common TEAE leading to rituximab interruption in 8%.
Discussion:
These data represent complete analysis of all patients in the induction phase of MAGNIFY which continue to support that R 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.