Ushering in a New Combination-Driven Era in MCL

Early data with sonrotoclax presented at ASH 2025 reflect evolving treatment paradigms in mantle cell lymphoma (MCL), particularly the move away from traditional chemoimmunotherapy. Drawing on long-standing principles in oncology drug development, Michael Wang, MD, emphasizes that new agents are first evaluated as monotherapy in the relapsed/refractory setting to establish intrinsic activity, safety, and durability of response. Based on early findings, sonrotoclax has demonstrated encouraging response rates and a meaningful duration of response as a single agent, supporting its potential role in heavily pretreated and BTK inhibitor–refractory patients.

From there, the discussion shifts to combination strategies, which have historically driven the most durable outcomes in cancer care. In MCL, prior experience has shown that combining targeted agents—such as CD20 monoclonal antibodies, BTK inhibitors, and BCL2 inhibitors—can outperform single agents. Sonrotoclax is positioned as a key component of future doublet and triplet regimens, with the expectation that, following regulatory approval, multiple combination studies will further define its optimal use. The interview highlights that while strong responses are seen in the relapsed setting, outcomes often improve substantially when effective combinations are moved earlier in the treatment course.

Wang notes that prior frontline studies combining 3 mechanistically distinct therapies have achieved near-universal response rates and prolonged remissions lasting 4 to 5 years, raising the possibility of functional cure when disease is treated early. Looking ahead, sonrotoclax-based regimens may extend beyond targeted combinations to include bispecific antibodies and CAR T-cell therapies, further reshaping the MCL treatment landscape. The new data underscore growing optimism that innovative, chemo-free combinations anchored by agents like sonrotoclax can meaningfully improve long-term outcomes for patients with MCL.