PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA IN THE MAGNIFY PHASE 3B INTERIM ANALYSIS OF INDUCTION R2 FOLLOWED BY MAINTENANCE

Abstract

Relapse is expected when treating patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL), with a shortened response associated with each relapse. Lenalidomide combined with rituximab (R 2 ) has shown enhanced activity, with a recently reported median progression free-survival (PFS) of 39.4 months in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma, including those with FL and MZL (Augment; J Clin Oncol. 2019;37:1188). MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), MZL, and mantle cell lymphoma (MCL). Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m 2 /wk cycle 1 and then every 8 wk starting with cycle 3 (R 2 ) is given for 12 cycles followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R 2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group criteria. Secondary end points include safety, CR rate, duration of response (DOR), duration of CR, time-to-response, time-to-next antilymphoma therapy, and overall survival. Data presented here focus on induction R 2 in efficacy-evaluable patients with MZL compared with the overall population of FL grades 1–3a+MZL (not including FL grade 3b, tFL, or MCL) receiving ≥ 1 treatment with baseline/post-baseline assessments. As of August 28, 2020, 394 patients with FL grades 1–3a and MZL enrolled; 76 (19%) had MZL. The median age of patients with MZL was 68 years (range, 46–90), 68 (89%) had stage III/IV disease, and 72 (95%) had prior rituximab-containing therapy. Overall response rate in the MZL and overall population was 66% and 75% with 39% and 44% having a CR/CRu. Median DOR was 38.6 months (95% CI, 29.4–not reached [NR]) and NR (95% CI, 38.6–NR). The median PFS was 40.9 months (95% CI, 27.8–NR) and 41.2 months (95% CI, 38.7–NR). In the MZL population, 43 patients (57%) have completed 12 cycles of R 2 , and 42 (55%) have been randomized and entered maintenance. Twenty-eight patients (37%) prematurely discontinued both lenalidomide and rituximab, primarily due to adverse events (AEs; n = 11; 14%) and progressive disease (n = 6; 8%). The most common (≥ 20%) all-grade AEs were neutropenia (49%), fatigue (43%), diarrhea (37%), thrombocytopenia (24%), constipation (24%), and anemia (22%). Most common (≥ 10%) grade 3/4 AEs were neutropenia (41%; 1 patient [1%] had febrile neutropenia), thrombocytopenia (13%), and leukopenia (13%). R 2 is active with a tolerable safety profile in patients with R/R MZL. The efficacy and safety profile of R 2 in patient with MZL were similar to results observed in the overall MAGNIFY population. These results suggest that R 2 should be considered as a therapeutic option for patients with R/R MZL.