Dr Hoffmann on the Significance of Efficacy Data for Sonrotoclax Plus Zanubrutinib in MCL

“You have to crawl before you can walk, and [BGB-11417-101] was the crawl study. We demonstrated safety and efficacy for [sonrotoclax plus zanubrutinib]…This is a promising strategy that reinvigorates the role of BCL2 inhibition in MCL, not just in combination with zanubrutinib, but in combinations with a lot of other agents.”

Marc S. Hoffmann, MD, an associate professor of Hematologic Malignancies and Cellular Therapeutics, medical director of Lean and Quality Improvement and the Lymphoma Program at The University of Kansas Medical Center, discussed data for sonrotoclax (Beqalzi) plus zanubrutinib (Brukinsa) for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) from the phase 1/1b BGB-11417-101 trial (NCT04277637) which was presented at the 2026 EHA Congress.

Patients who were treated at the 320-mg per day recommended phase 2 dose of sonrotoclax (n = 27) experienced an overall response rateof 81.5%, in addition to a complete response (CR) rate of 59.3%. The median time to CR was 5.2 months (range, 1.5-32.5), with the median duration of response and progression-free survival were both not reached at data cutoff. Notably, one instance of grade 3 atrial fibrillation occurred, and no clinical tumor lysis syndrome (TLS) was observed.

Hoffmann pointed out how now new safety signals were observed with the combination, and the regimen was ultimately well tolerated in the trial. Moreover, rates of hematologic toxicities were low among patients who received the combination, he underscored. After touching on the efficacy data shown for the combination, Hoffmann mentioned that the lead-in period for zanubrutinib was a limitation for the study that caused some patients to be refractory to BTK inhibitor monotherapy, adding that the positive safety data shown indicate flexibility with lead-in periods for future trials.

Hoffmann then highlighted upcoming trials evaluating the combination, like the phase 3 CELESTIAL-RRMCL trial (NCT06742996), which is currently accruing; this study is randomly assigning patients with relapsed/refractory MCL to received sonrotoclax plus zanubrutinib or placebo plus zanubrutinib. Ultimately, he concluded by emphasizing how further trials may help provide clinical practice with concrete data to help inform decisions, and Hoffman hopes see more data on how the combination compares with others in the MCL treatment paradigm.