Phase Ib Trial Finds Acalabrutinib Plus Venetoclax and Rituximab Induces 'Durable' Responses in MCL

The combination of acalabrutinib plus venetoclax and rituximab (AVR) is well tolerated and induces durable and deep clinical and molecular responses in patients with treatment-naïve mantle cell lymphoma (MCL), according to a phase Ib study.

The results of the two-year safety and efficacy analysis were presented in a poster session at the 2022 American Society of Hematology Annual Meeting by Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues.

The open-label, single-arm, multicenter, phase Ib study enrolled adults with treatment-naïve MCL who received acalabrutinib plus rituximab for six 28-day cycles with maintenance rituximab for up to two years for responders and oral acalabrutinib continuously until progressive disease or intolerable toxicity. Venetoclax started at cycle two with a standard five-week ramp-up to 400 mg/day and continued for two years.

The study enrolled 21 patients (median age, 66 years; range, 51–85). In terms of clinical characteristics, 90.5% [n=19] had Ann Arbor stage IV disease, 71.4% [n=15] had initial bone marrow involvement, 19% [n=4] had a high-risk simplified Mantle Cell lymphoma International Prognostic Index score, and 4.8% [n=1] had blastoid histology.

At data cutoff (March 29, 2022), 15 patients (71.4%) remained in the study, while five (23.8%) died of COVID-19, and one (4.8%) started new therapy.

Treatment response was assessed by clinical examination, computed tomography (CT), and positron emission tomography (PET) by Lugano criteria. The overall response rate was 100% (n=21), complete response rate was 90% (n=19), and partial response rate was 10% (n=2) by PET/CT.

Median time to initial response and best response were 2.8 (range, 0.7-5.6 months) and 3.0 (range, 0.7-18.3 months) months, respectively. Median duration of response was not reached even after censoring COVID-19 deaths. With a median follow-up of 25.8 months (range, 8.0-38.5 months), the median progression-free survival (PFS) and overall survival were not reached. PFS rates at one and two years were 90% (95% CI, 65.6-97.4) and 54.4% (95% CI, 21.6-78.5), respectively (both were 94.7% [95% CI, 68.1-99.2] after censoring COVID-19 deaths)

“This study strongly supports further clinical investigation of AVR for treatment-naïve MCL,” the authors wrote.

Reference

Wang M, Robak T, Maddocks K, et al. Acalabrutinib plus venetoclax and rituximab in patients with treatment-naïve (TN) mantle cell lymphoma (MCL): 2-year safety and efficacy analysis. Abstract #2884. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.