Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis

Abstract

AbstractThis phase 1b study (NCT02717624) evaluated the safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.2% completed induction (6 AVR cycles) and 47.6% continued maintenance with acalabrutinib. Thirteen (61.9%) patients had grade 3 to 4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had coronavirus disease 2019 (COVID-19) infection (6 [28.6%] serious AEs and 5 [23.8%] deaths, all among unvaccinated patients). There were no grade ≥3 events of atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) by Lugano criteria was 100% (95% confidence interval [CI], 83.9-100.0) with a 71.4% complete response. With a median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The PFS rates at 1 and 2 years were 90.5% (95% CI, 67.0-97.5) and 63.2% (95% CI, 34.7-82.0), respectively; both were 95% after censoring for COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI, 70.7-99.3) and 75.2% (95% CI, 50.3-88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of the patients with available minimal residual disease (MRD) data achieved MRD negativity (10–6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity. The trial was registered at www.ClinicalTrials.gov as #NCT02717624.