COMBINATION OF IBRUTINIB WITH RITUXIMAB (IR) IS HIGHLY EFFECTIVE IN PREVIOUSLY UNTREATED ELDERLY (>65 YEARS) PATIENTS (PTS) WITH MANTLE CELL LYMPHOMA (MCL) – PHASE II TRIAL

Introduction: We reported the efficacy of ibrutinib with rituximab (IR) combination in relapsed MCL. Here we present the first efficacy/safety analysis of single center, phase II clinical trial of IR combination in untreated elderly pts with MCL. Methods: Previously untreated elderly (>65 years) MCL pts (n=42) were enrolled in this study (NCT01880567). Pts with Ki-67% ≥ 50% and blastoid/pleomorphic histology were excluded. 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 safety and the efficacy. Among evaluable samples, minimal residual disease (MRD) by flow cytometry at best response and other molecular studies for clonal evolution at various time points were performed. Results: The median age was 71 years (range 65-84), ECOG PS was (0/1) in 41 (98%) pts, 20% had high risk MIPI score, Ki-67% was low (<30%) in 30 (73%) and high (≥30-50%) in 11 (27%) pts, and 10% had complex karyotype. Median number of IR cycles was 19 (1-43). Best overall response (ORR) was 95% (69% CR, 26% PR, 5% stable disease). Median number of IR cycles to reach CR 4 (2-31). Thirty two patients had PET- based response assessment and all had CR (100%). MRD negative CR by flow cytometry was 65%. Overall, the median follow up was 24 months (6-42). Median PFS and OS were not reached. Among pts with low and high Ki-67%, median PFS was (not reached; p=0.28) and OS (not reached; p=0.02). Median duration on study was 19 months (range 1-39). Overall, 4 pts progressed (2 transformed to blastoid MCL) on study after taking IR for 4, 9, 13 and 32 months. Two pts died. At the time of last follow up, 24 pts remained on study and 18 (43%) discontinued therapy. Dose reduction was performed in 23 (55%) pts for various reasons. Most frequent grade 3-4 toxicities were 17% myalgias, 14% fatigue, 12% shortness of breath, 9% neutropenia and 5% new onset atrial fibrillation. Conclusions: IR combination in elderly pts with MCL as a frontline treatment was very effective and safe. This strategy provides an excellent frontline alternate to chemotherapy in elderly pts with MCL. Keywords: ibrutinib; mantle cell lymphoma (MCL). Disclosures: Wang, M: Consultant Advisory Role: Pharmacyclics and Janssen.