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

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other B-Cell Lymphomas: Clinical and Epidemiological: Follicular Lymphoma: Advances in Treatment Approaches
Hematology Disease Topics & Pathways:
Clinically Relevant
Monday, December 13, 2021: 4:45 PM

Frederick Lansigan, MD1, David Jacob Andorsky, MD2, Morton Coleman, MD, FACP3*, Abdulraheem Yacoub, MD4, Jason Melear, MD5, Suzanne Fanning, DO6, Kathryn S. Kolibaba, MD7, Christopher M. Reynolds, MD, BA8, Grzegorz S. Nowakowski, MD9, Mecide Gharibo, MD10, Jung Ryun Ahn, MD10*, Ju Li, PhD10*, Mathias J. Rummel, MD, PhD11* and Jeff P. Sharman, MD12

1Dartmouth-Hitchcock Medical Center, Lebanon, NH
2Rocky Mountain Cancer Centers, US Oncology Research, Boulder, CO
3Clinical Research Alliance Inc, Weill Cornell Medicine, New York, NY
4University of Kansas Cancer Center, Westwood, KS
5Texas Oncology — Austin, US Oncology Research, Austin, TX
6Prisma Health, US Oncology Research, Greenville, SC
7US Oncology Research, Vancouver, WA
8IHA Hematology Oncology Consultants — Ann Arbor, Ypsilanti, MI
9Mayo Clinic, Rochester, MN
10Bristol Myers Squibb, Princeton, NJ
11Justus-Liebig-Universität, Giessen, Germany
12Willamette Valley Cancer Institute and Research Center, US Oncology Research, Eugene, OR

Background: Patients with relapsed indolent NHL (iNHL) have limited standard treatment options. Lenalidomide combined with rituximab (R2) has shown complimentary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) patients with iNHL (RELEVANCE: N Engl J Med 2018;379:934 and AUGMENT: J Clin Oncol. 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/m2/week cycle 1 and then every 8 weeks starting with cycle 3 (R2) are administered for 12 cycles. Patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) were randomized 1:1 to R2 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 (Table). All patients have completed R2 induction (n = 232, 59%) or discontinued study treatment (n = 162, 41%). 141 patients (36%) prematurely discontinued both lenalidomide and 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). Efficacy results are reported in the table by histology subgroups (FL vs MZL), and rituximab-refractory, double-refractory, and early relapse statuses. 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.

Conclusions: These data represent complete analysis of all patients in the induction phase of MAGNIFY which continue to support that R2 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.

Disclosures: Lansigan: Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Andorsky: Abbvie: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Epizyme: Research Funding. Coleman: immunomedics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Abbvie: Research Funding; Bristol Myers: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Gilead: Research Funding; BeiGene: Research Funding; Innocare: Research Funding; Merck: Research Funding; Pfizer: Research Funding; Roche: Research Funding. Yacoub: Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company. Melear: TG Therapeutics: Speakers Bureau; Astrazeneca: Speakers Bureau; Janssen: Speakers Bureau. Fanning: Sanofi: Speakers Bureau; Genmab: Membership on an entity's Board of Directors or advisory committees; TG Pharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau. Kolibaba: TG Therapeutics: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Atara Biotechm: Consultancy; McKesson Specialty Health: Consultancy; Sunitomo Dainippon Pharma: Consultancy; Tolero Pharma: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Nowakowski: Incyte: Consultancy; Kymera Therapeutics: Consultancy; TG Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Curis: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; MorphoSys: Consultancy; Karyopharm Therapeutics: Consultancy; Zai Labolatory: Consultancy; Daiichi Sankyo: Consultancy; Bantham Pharmaceutical: Consultancy; Genentech: Consultancy, Research Funding; Kyte Pharma: Consultancy; Ryvu Therapeutics: Consultancy; Selvita: Consultancy; Roche: Consultancy, Research Funding; Nanostrings: Research Funding. Gharibo: BMS: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Ahn: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; ADC therapeutics: Current equity holder in publicly-traded company. Li: BMS: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding. Sharman: Pharmacyclics LLC, an AbbVie Company: Consultancy; BeiGene: Consultancy; Lilly: Consultancy; Bristol-Myers Squibb: Consultancy; AbbVie: Consultancy; AstraZeneca: Consultancy; TG Therapeutics: Consultancy; Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Velos: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH