ASCO 2021 | Safety and efficacy of zanubrutinib in patients with B-cell malignancies
Mazyar Shadman, MD, Fred Hutchinson Cancer Research Center, Seattle, WA, shares an update on the preliminary results of the Phase II BGB-3111-215 trial (NCT04116437) of zanubrutinib for patients with previously treated B-cell lymphoma who are intolerant to prior BTK inhibitor therapy. At 4.2 months of follow up, 24/43 patients had reported an adverse event. Grade three or higher adverse events were reported in six patients and a serious adverse event was reported in one patient. No adverse events led to zanubrutinib discontinuation. All patients evaluable for efficacy maintained or achieved deepening of their response. Dr Shadman comments on these findings, comparing events which occurred with ibrutinib or acalabrutinib therapy to those which occurred with zanubrutinib therapy. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
At the EHA meeting, 2021, we have results of our Phase II study of zanubrutinib in patients with previously treated B-cell malignancies who were intolerant to either ibrutinib, acalabrutinib or both. So, the idea was to see if zanubrutinib as a second-generation BTK inhibitor could be better tolerated in patients who had to stop ibrutinib or acalabrutinib. Remember that these patients could not have had disease progression on one of the two drugs...
At the EHA meeting, 2021, we have results of our Phase II study of zanubrutinib in patients with previously treated B-cell malignancies who were intolerant to either ibrutinib, acalabrutinib or both. So, the idea was to see if zanubrutinib as a second-generation BTK inhibitor could be better tolerated in patients who had to stop ibrutinib or acalabrutinib. Remember that these patients could not have had disease progression on one of the two drugs. So, this is really a study that tries to see how feasible and how reliable zanubrutinib is in the post-ibrutinib, post-acalabrutinib, when patients switch because of intolerance.
So, we presented the first basically results at ASH 2020 and this is a larger number of patients at two cohorts. Ibrutinib only and acalabrutinib exposure for the second cohort, a total of 64 patients. I would just say maybe the take home message is that the zanubrutinib was very well tolerated in both cohorts. 75% of events, intolerance events, on both ibrutinib or acalabrutinib did not occur on zanubrutinib, which is I think clinically meaningful numbers. 75% of adverse events that were led to discontinuation did not occur.
With the events that occurred on zanubrutinib, 90% of those from the ibrutinib cohort were at the lower grade, 33% of the AEs that happened on acalabrutinib were at the lower grade. 10% of the ibrutinib side effects and 60% of the acalabrutinib side effects occurred at the same severity. We did not have any event that recurred at the higher severity, which again, this only happened in smaller percentage of patients that they had the recurrence of AEs, but even if it happened, it was either the lower grade or the same grade. So, we did not have that higher grade toxicity on zanubrutinib.
None of the patients had to stop the drug because of intolerance and of course the drug remains to be very effective and disease control was really high. So, I think that this is an important study in showing that patients who did not tolerate ibrutinib or acalabrutinib, zanubrutinib could be a viable option. The study will focus from now on more on patients who came off acalabrutinib for intolerance issues and hopefully we will have more data to present in future meetings or in the form of publications.
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