Kumar A, Batlevi C, Drullinsky P, et al. - Given bendamustine (B) and rituximab (R) with ibrutinib (IBR) showed good tolerability and efficacy (Maddocks Blood 2015), researchers undertook this phase I study to test the safety as well as tolerability of ibrutinib and venetoclax (VEN) with BR-IBR in relapsed, refractory (R/R) MCL. Patients (pts) suffering from R/R MCL were administered six 28-day cycles of BR-IBR-VEN in a 3+3 dose escalation design. Dose level 1 (DL1) involved B 90 mg/m2 day (d) 1 and 2, R 375 mg/m2 d1, and IBR 560mg daily. For cycle 1, VEN dose ramp-up was 20, 50, 100, and 200mg daily weekly. VEN 400mg daily was administered d1-5 during cycles 2-6. The study was amended to include dose level -1 (DL-1) with B at 70mg/m2, d1 and 2. At DL1, there occurred one dose limiting toxicity (DLT): grade 3 thrombocytopenia lasting >14 days. Neither DLTs, dose reductions or delays, significant cytopenias, nor ≥grade 3 tx(one prior line of treatment)-related adverse events occurred at DL-1 (n = 3). An overall response rate of 80% (8/10) was obtained, all complete responses. Findings demonstrated acceptable safety and tolerability as well as preliminary efficacy of BR-IBR-VEN at DL-1. Due to COVID pandemic, the study was closed post-enrollment of 3 of 6 pts at DL-1 and a definitive maximum tolerated dose was not ascertained.