Patients with Relapsed/Refractory Marginal Zone Lymphoma in the MAGNIFY Phase IIIb Interim Analysis of Induction R2 Followed By Maintenance
Authors: Coleman Morton , Andorsky David Jacob , Yacoub Abdulraheem , Melear Jason M. , Fanning Suzanne R. , Kolibaba Kathryn S. , Lansigan Frederick , Reynolds Christopher M. , Nowakowski Grzegorz S. , Gharibo Mecide , Ahn Erin , Li Ju , Rummel Mathias J. , Sharman Jeff P 
Published: November 2020

Background: 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 (R2) 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).
Methods: MAGNIFY is a multicenter, phase IIIb trial in patients with R/R FL grades 1-3b, transformed FL (tFL), MZL, or mantle cell lymphoma (MCL; NCT01996865) in which optimal lenalidomide duration is being explored. Patients received 12 cycles of R2 (lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2 weekly in cycle 1 and then on day 1 of cycles 3, 5, 7, 9, and 11) followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 versus rituximab maintenance for 18 months. Data presented here focus on induction R2 in efficacy-evaluable MZL patients 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. The primary end point is progression-free survival (PFS) by 1999 International Working Group criteria.
Results: As of November 30, 2019, 393 patients with FL grades 1-3a and MZL enrolled; 76 (19%) had MZL. The median age of MZL patients was 68 years (range, 46-90), 68 (89%) had stage III/IV disease, and 72 (95%) had prior rituximab-containing therapy. Overall response rate was 68% with 39% CR/CRu, and median duration of response was 38.6 months (95% CI, 29.4-not reached [NR]). The median PFS was 41.2 months (95% CI, 38.4-NR). Efficacy results for MZL subtypes and the overall population (FL grades 1-3a + MZL) are shown in the table. Forty-two patients (55%) have completed 12 cycles of R2, and 41 (54%) 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%), diarrhea (37%), anemia (25%), thrombocytopenia (24%), and constipation (24%). Most common (≥ 10%) grade 3/4 AEs were neutropenia (41%; 1 patient [1%] had febrile neutropenia), thrombocytopenia (13%), and leukopenia (11%).
Conclusions: R2 is active with a tolerable safety profile in patients with R/R MZL. The efficacy and safety profile of R2 in MZL patients were similar to results observed in the overall MAGNIFY population.

Disclosures
Coleman: Seattle Genetics: Research Funding; EMD Serono Research and Development Institute Inc.: Research Funding; Innocare: Research Funding; ARCUS Biosciences: Research Funding; AstraZeneca Pharmaceuticals, LP (Acerta Pharma BV Trials): Research Funding; AstraZeneca Pharmaceuticals, LP: Research Funding; BMS (Celgene Corporation): Research Funding; Eli Lilly and Company: Research Funding; Genetech (F. Hoffman-LaRoche Ltd): Research Funding; Hutchinson MediPharma, LTD: Research Funding; Ipsen Group: Research Funding; Karyopharma Therapeutics, Inc.: Research Funding; Klus Pharma, Inc.: Research Funding; MeiPharma, Inc.: Research Funding; Merck Sharp & Dohme Corp.: Research Funding; Novartis Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; Boston BIoMedical, Inc.: Research Funding; BeiGene: Research Funding; Acerta: Research Funding. Andorsky:CTI: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Research Funding. Yacoub:Roche: Other: Support of parent study and funding of editorial support; Dynavax: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Incyte: Speakers Bureau; Hylapharm: Current equity holder in private company; Cara Therapeutics: Current equity holder in publicly-traded company; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau. Melear:Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau. Fanning:Takeda: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; TG Therapeautics: Consultancy; Abbvie: Consultancy; Prisma Health: Current Employment; Sanofi Aventis: Speakers Bureau. Kolibaba:Atara Biotech: Consultancy; Compass Oncology: Ended employment in the past 24 months; Verastem: Honoraria; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Novartix: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Sumitomo Dainippon Pharma Oncology: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lansigan:BMS: Consultancy; Seattle Genetics: Consultancy; BMS Steering Committee for MAGNIFY Program: Membership on an entity's Board of Directors or advisory committees; Spectrum Pharma: Consultancy, Research Funding. Reynolds:IHA Hematology/Oncology Consultants: Current Employment. Nowakowski:Kymera: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Curis: Consultancy; Kite: Consultancy; MorphoSys: Consultancy, Research Funding; Denovo: Consultancy; Seattle Genetics: Consultancy; Nanostrings: Research Funding; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding. Gharibo:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Bayer: Ended employment in the past 24 months. Ahn:BMS: Current Employment, Current equity holder in publicly-traded company. Li:BMS: Current Employment, Current equity holder in publicly-traded company. Rummel:Roche: Honoraria; Amgen GmbH: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Honoraria; Novartis Pharma GmbH: Honoraria. Sharman:BeiGene: Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.