In a phase 1b trial, the combination therapy of acalabrutinib, venetoclax, and rituximab had a 100% clinical response rate and was well-tolerated in patients with treatment-naïve mantle cell lymphoma.
The combination therapy of acalabrutinib, venetoclax, and rituximab (AVR) had a 100% clinical response rate and was well-tolerated in patients with treatment-naïve (TN) mantle cell lymphoma (MCL), according to data from an ongoing, multicenter, open-label phase 1b study presented at the American Society of Hematology’s Annual Meeting and Exposition 2021.
During the study, investigators enrolled 21 patients with TN MCL aged 18 years or older with Eastern Cooperative Oncology Group Performance Status ≤2; bone marrow involvement was observed in 71% of these patients at baseline. Acalabrutinib was administered at 100mg twice a day starting on cycle 1 on day 1 and continuing until disease progression or discontinuation for any reason. Rituxumab was administered at 375 mg/m2 on day 1 of each 28-day cycle for 6 cycles, followed by maintenance during every other cycle for patients achieving complete response (CR) or partial response (PR), through cycle 24. Venetoclax was administered via an initial 5-week ramp-up schedule, starting on cycle 2 on day 1 and continuing through cycle 25, with 400mg daily administered after ramp-up.
The primary endpoint of the study was AVR safety, and dose-limiting toxicity (DLT) was assessed from cycle 2 on day 1 to cycle 3 on day 28. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS) per Lugano criteria. At the end of cycle 6, the ORR was 100%. Median DOR was 19 months overall, but was not reached due to 3 patients with COVID-19 related deaths being removed from the analysis. Median PFS and OS were not reached.
According to the investigators, no DLTs were observed. The most common adverse events (AEs) of any grade observed in at least 20% of patients included diarrhea, headache, fatigue, neutropenia, paresthesia, cough, dyspnea, myalgia, dizziness, and hypoesthesia. Grade 3/4 AEs occurring in 2 or more patients included neutropenia and pneumonia. AEs led to dose holds in 57% of patients and were associated with acalabrutinib in 52% of these cases, venetoclax in 48%, and rituximab in 14%.
Wang M, Robak T, Maddocks KJ, et al. Safety and efficacy of acalabrutinib plus venetoclax and rituximab in patients with treatment-naïve (TN) mantle cell lymphoma (MCL). Presented at: ASH Annual Meeting and Exposition 2021. Accessed December 10, 2021. https://ash.confex.com/ash/2021/webprogram/Paper146615.html