Dr Phillips on the Preliminary Efficacy of Acalabrutinib Plus BR in MCL

Tycel Phillips, MD, MPH, associate clinical professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the updated safety profile and clinical activity seen with the addition of acalabrutinib (Calquence) to bendamustine and rituximab (Rituxan; BR) in patients with mantle cell lymphoma (MCL).

The phase 1 trial (NCT02717624) was conducted in patients with either treatment-naïve (n = 18) or relapsed/refractory MCL (n = 20). Patients received the regimen for 6, 28-day cycles. Patients in the previously untreated cohort who responded to the regimen received subsequent maintenance acalabrutinib and rituximab for up to 2 years. Both cohorts were given continuous oral acalabrutinib until disease progression or treatment discontinuation due to unacceptable toxicity. The study’s primary end point was safety. Key secondary end points were overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR) per Lugano criteria.

Data presented at the 2023 ASCO Annual Meeting showed that the triplet regimen produced an ORR of 89.5% in the overall population, with a complete response (CR) rate of 73.7%. Patients in the treatment-naïve cohort experienced an ORR of 94.4% with the combination. This consisted of a CR rate of 77.8% vs 88.9% according to PET-CT alone, Phillips expands. At a median follow-up of 47.6 months, both median PFS and median DOR were not reached in this cohort, he adds. Twelve- and 36-month PFS rates in this population were 88.5% and 68.1%, respectively.

Conversely, the ORR based on Lugano criteria in the relapsed/refractory population was 85%, including a CR rate of 70%, Phillips states. The CR rate with PET-CT alone was 80%, he notes. Median PFS was 28.6 months and median DOR was 43.5 months at a median follow-up of 20.4 months. The 12-month PFS rate was 73%, and the 36-month PFS rate was 47.3%.

The chemoimmunotherapy combination was also deemed safe and tolerable, although there was a high frequency of grade 3/4 adverse effects (AEs). No significant cardiac events were observed, Phillips states. However, more follow-up analysis may reveal some additional signals, he says. Additionally, the regimen was associated with an increased risk of infection, Phillips notes. The most common any-grade AEs of interest across both groups were neutropenia (60.5%), infections (73.7%), hemorrhage (36.8%), and cardiac events (21.1%). The high incidence of both neutropenia and infection can likely be attributed to the addition of acalabrutinib to this regimen, he concludes.