Triplet Combination Assessed for Safety, Efficacy in Patients with MCL

The combination of acalabrutinib, venetoclax, and obinutuzumab (AVO) is a safe and feasible treatment option for patients with relapsed or refractory mantle cell lymphoma (MCL), according to a multicohort study presented at the 65th ASH Annual Meeting & Exposition.

The phase I/II trial, led by Austin Kim, MD, of the Dana-Farber Cancer Institute, aimed to establish the recommended phase II dose of AVO in relapsed or refractory MCL. All patients had advanced-stage MCL and received a median of one prior treatment.

The study evaluated up to two dose levels of oral acalabrutinib, starting with the FDA-approved dose of 100 mg twice daily in cycle one, followed by a lower dose of 100 mg once a day if dose-limiting toxicities (DLTs) occurred in more than a sixth of patients.

Patients received intravenous obinutuzumab in cycle two (100 mg on day one, 900 mg on day two, 1000 mg on days eight and 15) and in cycles three to seven. The weekly venetoclax dose was increased in cycle three to a target dose of 400 mg daily. Acalabrutinib and venetoclax were continued indefinitely, and obinutuzumab maintenance was administered every two cycles—beginning with cycle nine—for 12 doses.

The twice-daily dose of acalabrutinib was deemed the recommended phase II dose. After a median follow-up of six months, the overall response rate was 78%, and the complete response rate was 67% after three cycles of AVO. Median overall survival and progression-free survival were not reached.

No DLTs occurred in the nine evaluable patients in the twice-daily dosing acalabrutinib cohort. The most common toxicities included headache, bruising, diarrhea, and upper respiratory infection. Hematologic toxicities included neutropenia, thrombocytopenia, and anemia.

Reference

Kim A, Armand P, Redd R, et al. Phase I safety and preliminary efficacy of acalabrutinib, venetoclax, and obinutuzumab (AVO) in patients with relapsed/refractory mantle cell lymphoma. Abstract #3031. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.