PHASE IIIB STUDY OF LENALIDOMIDE PLUS RITUXIMAB FOLLOWED BY MAINTENANCE IN RELAPSED OR REFRACTORY NHL: ANALYSIS OF MARGINAL ZONE LYMPHOMA

Abstract

Introduction: Lenalidomide combined with rituximab (R2) has shown synergistic effects in preclinical settings. R2 is also clinically active and tolerable non-chemotherapy regimen in untreated and relapsed or refractory (R/R) patients with indolent non-Hodgkin lymphoma (NHL), including marginal zone lymphoma (MZL). The clinical potential of R2 supports further study in MZL and its subtypes. Method(s): MAGNIFY (NCT01996865) is a phase IIIb, multicenter, open-label study of R/R NHL patients with grades 1-3b follicular lymphoma (FL; including transformed FL), MZL, and mantle cell lymphoma (MCL). Patients receive 12 cycles of R2(oral lenalidomide 20 mg/d, d1-21 of a 28-d cycle; intravenous rituximab 375 mg/m2, d1, 8, 15, 22 of cycle 1 and d1 of subsequent odd cycles). Following R2 induction, those with stable disease or better are randomized 1:1 to maintenance R2 (oral lenalidomide 10 mg/d, d1-21 of a 28-d cycle; rituximab 375 mg/m2, d1 of every other cycle) or rituximab alone (375 mg/m2, d1 of every other cycle). The primary endpoint is progression-free survival (PFS); secondary endpoints include safety, overall survival, and response rates. This analysis focuses on MZL and includes the 3 subtypes: MALT, splenic MZL, and nodal MZL. Result(s): As of April 14, 2016, the R/R NHL population (N = 155) was composed of 27 (17%) patients with MZL, including 13 nodal MZL, 8 splenic MZL, and 6 MALT (4 without gastric involvement). The median age of MZL patients was 65 y (range, 46-85), most (81%) with stage III/ IV disease at study entry and all with ECOG PS 0-1. Patients with MZL had a median of 1 prior treatment regimen (range, 1-4), with 8 (30%) patients having >=2. The most common prior therapies were rituximab alone (44%), bendamustine/rituximab (BR; 26%), or R-CHOP-like regimens (26%); 37% were refractory to rituximab, defined as best response of SD/PD to rituximab/R-containing regimen or CR/PR <6 mo after last rituximab dose. The overall response rate (ORR) during induction in 22 evaluable MZL patients was 55% (45% CR/CRu); response assessment was too early with no reported efficacy in nonevaluable patients. Responses by subtype are shown in Table 1. The most common grade 3/4 treatment-emergent adverse events in MZL patients during induction were hematologic, 9 (33%) neutropenia and 3 (11%) thrombocytopenia. Conclusion(s): R2 induction showed favorable activity and tolerable safety profiles in R/R patients with MZL. Enrollment in MAGNIFY is ongoing. (Table Presented).