Frontline Treatment with Ibrutinib with Rituximab (IR) Combination Is Highly Effective in Elderly (≥65 years) Patients with Mantle Cell Lymphoma (MCL) - Results from a Phase II Trial

Background - Mantle cell lymphoma (MCL) generally affects patients with a median age of 71 years. Majority of elderly MCL patients are transplant ineligible and are not suitable for intensive chemoimmunotherapy. Considering these limitations, our efforts are focused on developing “chemotherapy-free” modalities to treat these patients. We have previously reported high efficacy from a combination of ibrutinib with rituximab (IR) in relapsed MCL (Wang M et al Lancet Oncology 2015). We will now present the efficacy/safety analysis of our single center, phase II clinical trial using IR in previously untreated elderly (age ≥65 years) patients (pts) with MCL. Methods - We enrolled previously untreated elderly (≥65 years) MCL pts (n=50) in this study (NCT01880567). Pts with Ki-67% ≥ 50%, blastoid/pleomorphic histology and those with clinically uncontrolled co-morbidities (including atrial fibrillation) were excluded from this study. Pts received IR combination - ibrutinib 560 mg orally daily for 28 days (one cycle) continued until disease progression or discontinued for any reason. Rituximab was given on days 1, 8, 15 and 22 +/- 1 day by intravenous infusion (IV) at a fixed dose of 375 mg/m2 (Cycle 1, followed by rituximab on day 1 of every cycle starting in Cycles 3 - 8. Following cycle 8, rituximab was given on day 1 of every other cycle for up to 2 years. The primary objective was to assess the response rate and safety of IR in elderly MCL. Among evaluable samples, minimal residual disease (MRD) by flow cytometry at best response and whole exome sequencing (WES) from baseline tissue samples was performed. Results - Forty nine pts were included in this analysis. Median age was 71 years (range 65-84), 75% were males, ECOG PS was (0/1) in 48 (98%) pts, 16% had high risk simplified MIPI score and 28% had high risk biologic MIPI score. Forty seven patients (96%) had initial bone marrow involvement by MCL. The Ki-67% was low ( Conclusions - IR combination is an excellent frontline treatment option for elderly pts with MCL. Pts with baseline arrhythmias or pre-existing cardiac comorbidities could be managed cautiously and successfully while on this combination and are recommended to closely follow up with cardiology and may need an adjustment of anti-arrhythmic or ibrutinib dosing for optimal management. Download : Download high-res image (331KB) Download : Download full-size image Disclosures Lee: Seattle Genetics, Inc.: Research Funding. Westin: Juno: Other: Advisory Board; 47 Inc: Research Funding; Unum: Research Funding; Celgene: Other: Advisory Board, Research Funding; Novartis: Other: Advisory Board, Research Funding; Genentech: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding; Janssen: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Curis: Other: Advisory Board, Research Funding. Nastoupil: Spectrum: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding. Neelapu: Celgene: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Acerta: Research Funding; BMS: Research Funding; Cellectis: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Cell Medica: Consultancy; Pfizer: Consultancy; Precision Biosciences: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Karus: Research Funding; Poseida: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Allogene: Consultancy. Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang: Juno Therapeutics: Research Funding; Aviara: Research Funding; Acerta Pharma: Consultancy, Research Funding; Dava Oncology: Honoraria; Loxo Oncology: Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Kite Pharma: Consultancy, Research Funding; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding. OffLabel Disclosure: Ibrutinib and rituximab in frontline mantle cell lymphoma