PS1253 MAGNIFY: PHASE IIIB INTERIM ANALYSIS OF INDUCTION #R2 FOLLOWED BY MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON‐HODGKIN LYMPHOMA

Abstract

Background:There is a lack of standard treatment approaches for patients with relapsed indolent non‐Hodgkin lymphoma (iNHL). Current study results with PI3K inhibitors have reported a median PFS of <1 y in the relapsed/refractory setting (R/R) for patients with iNHL. Lenalidomide, an immunomodulatory agent, enhances the activity of rituximab when combined into a regimen known as R2, which has recently reported a median PFS of 39.4 mo in patients with R/R iNHL patients from the phase III AUGMENT study (Leonard. ASH 2018:445).Aims:These analyses examine the interim primary endpoint of overall response rate (ORR; 1999 IWG) for induction R2 in efficacy‐evaluable patients receiving ≥ 1 treatment and who have available baseline and post‐baseline assessments.Methods:The multicenter, non‐registrational phase IIIb MAGNIFY trial in patients with R/R follicular lymphoma (FL) grade 1–3a and marginal zone lymphoma (MZL) was designed to determine the optimal duration of lenalidomide (NCT01996865). R2 treatment includes lenalidomide 20 mg/d, d1–21/28 plus rituximab 375 mg/m2/wk cycle 1 and q8wk cycles 3+ given for 12 cycles, and is followed by 1:1 randomization in patients with stable disease or better to continued R2 vs rituximab maintenance.Results:370 enrolled patients (80% FL grade 1–3a; 20% MZL) had a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab‐containing). At a median 16.7 mo follow‐up, efficacy‐evaluable patients demonstrated a 73% ORR and 45% complete response (CR; Table). Similar efficacy results were shown for patients by histology. Overall, the median time to response (TTR) was 2.7 mo, median duration was response (DOR) was 36.8 mo, and median progression‐free survival (PFS) was 36.0 mo. According to their refractory status to rituximab at baseline, patients who were rituximab‐refractory and non‐refractory, respectively, had an ORR (CR) of 63% (40%) and 78% (47%), and median PFS of 18.1 mo and not reached. Of 370 patients who were randomized, 142 (38%) have entered the maintenance phase. The most common all‐grade adverse events were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Although the grade 3/4 adverse event neutropenia was 34%, all others were <6%.Summary/Conclusion:R2 therapy is an active treatment regimen in patients with R/R FL grade 1–3a and MZL, including patients refractory to rituximab, and with a tolerable safety profile.image