ASH 2024 | An update on zanubrutinib in acalabrutinib-intolerant B-cell malignancies: the BGB-3111-215 trial

At ASH 2024, we also presented a follow-up update on the 215 or SWITCH study, which is the study that looked at zanubrutinib in patients who are intolerant to acalabrutinib or ibrutinib. This was the general study. The presentation was focused on zanubrutinib in patients who were not tolerant to acalabrutinib in B-cell malignancies. As a quick reminder, this study took patients with different histologies, CLL, FL, mantle cell lymphoma, marginal zone lymphoma, or Waldenstrom. We had two cohorts. The first cohort, 57 patients who were intolerant to ibrutinib. What we’re reporting here is the second cohort or cohort two. These were patients who were intolerant to acalabrutinib and we have 35 patients. So these were patients who were having clinical benefit from acalabrutinib, but had to stop because of adverse events. And as long as they didn’t have progressive disease and prior BTKi, they could go on zanubrutinib. And again, as I mentioned, 35 patients were enrolled. 14 out of 35 patients were also previously intolerant to ibrutinib in addition to acalabrutinib, which was the main inclusion criteria. Now, one important number to remember, the cumulative acalabrutinib exposure was 5.7 months. So we’ll come back to this number. So in average, patients were on acalabrutinib for 5.7 months before being enrolled in the study. And basically, the study showed that as of the cut-off of the study, only 11 of 35 patients discontinued therapy and 88% remain on this study. Most of the acalabrutinib intolerance events, or to be exact, 69% did not recur at any grade with zanubrutinib. So it’s like almost 70% of adverse events did not come back. We also showed that the safety profile of zanubrutinib remained favorable. Fortunately, we did not have any AEs leading to death. And also among the 32 patients who had efficacy evaluable status, disease control rate was 93.8%. So patients either stayed in their good response or had an improvement of their response status. And one thing I wanted to highlight is remember the exposure time to acalabrutinib before coming on a study was 5.7 months. But if you look at the zanubrutinib exposure, it’s now 14.8 months. So it means that these patients had enough time to show the adverse events on zanubrutinib. One of the initial comments we got in this study was that the exposure time to zanubrutinib was relatively short. But here we’re showing that patients were on zanubrutinib much longer than the time they were on acalabrutinib. And despite that, the 70% of events did not recur. So basically the take-home point is that for patients who did not tolerate acalabrutinib, which is another great and well-tolerated BTK inhibitor, but for patients who have issues tolerating it, zanubrutinib remains to be a great option and provides a favorable safety and efficacy profile in that setting.

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