Experts Discuss Sonrotoclax and Lymphoma Trials at ASH 2025

Agrima Mian, MD Cleveland Clinic | Sam Yamshon, MD NYU Langone Health

Key Points

• Single-agent sonrotoclax, a novel B-cell lymphoma 2 (BCL2) inhibitor, showed very favorable outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

• Sonrotoclax has a shorter half-life and greater selectivity than venetoclax, potentially reducing toxicity.

• Bispecific antibody trials returned promising results in both indolent and aggressive lymphomas across treatment lines.

Sonrotoclax Monotherapy in MCL and Other Notable Lymphoma Trials

At the 2025 ASH Annual Meeting (ASH 2025), Agrima Mian, MD, of Cleveland Clinic, and Samuel Yamshom, MD, of NYU Langone Health, discussed one of the presentations for sonrotoclax, a next-generation BCL2 inhibitor, and considered the breadth of presentations in lymphoma at the meeting.

The phase 1/2 BGB-11417-201 trial enrolled patients with relapsed or refractory MCL previously treated with Bruton’s tyrosine kinase (BTK) inhibitor to receive sonrotoclax monotherapy. In the trial, sonrotoclax showed promising efficacy as a single agent, particularly in a population that had previously received one or more BTK inhibitors, said Dr. Yamshon. Venetoclax and other BCL2 inhibitors have shown the most potential in combination regimens, though toxicity can be a limiting factor. Due to its shorter half-life, sonrotoclax may improve the toxicity profile of these combinations, though more data are needed.

The doctors also discussed the variety of data presented at ASH 2025, showcasing the efficacy of bispecific antibodies in both indolent lymphomas and aggressive B-cell lymphomas across treatment settings. The EPCORE-FL1 data were particularly notable for their highly favorable efficacy and response outcomes. 

Moving forward, the question for bispecific antibodies, similar to sonrotoclax, may be how well they combine with other agents or how existing combinations can be modified, Dr. Yamshon said.