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BTK Inhibitor Zanubrutinib Under Study in the Treatment of Resistant DLBCL

By: Vanessa A. Carter, BS
Posted: Wednesday, May 25, 2022

The phase II BGB-3111-207 study, performed by Yufu Li, MD, PhD, of Henan Cancer Hospital, Zhengzhou, China, and colleagues, examined the safety and efficacy of zanubrutinib—a selective Bruton’s tyrosine kinase (BTK) inhibitor—in patients with relapsed or refractory nongerminal diffuse large B-cell lymphoma (DLBCL) in China. These results, which were published in Blood Advances, concluded that zanubrutinib was associated with a favorable safety and tolerability profile for the treatment duration.

“Antitumor activity observed in this patient population was modest and similar to the results from other studies that also evaluated the efficacy of BTK inhibitors as monotherapy,” concluded the study authors. “This pattern suggests that, in patients with relapsed or refractory nongerminal center DLBCL, additional studies should focus on the development of mechanism-based treatment combinations and biomarker-driven patient selection.”

This multicenter, open-label study enrolled 41 adult patients in China with histologically confirmed nongerminal center DLBCL who had no response to or relapsed after at least one prior therapy, as well as those who did not undergo bone marrow transplantation and intensive chemotherapy. Participants were administered 160 mg of oral zanubrutinib twice daily until unacceptable toxicity or disease progression.

At the median follow-up of 6.8 months, the overall response rate was 29.3%, and the complete response rate was 17.1%. The median duration of response, progression-free survival, and overall survival were 4.5, 2.8, and 8.4 months, respectively. Notably, oral zanubrutinib appeared to demonstrate potential antitumor activity in patients with both MYD88 and CD79B mutations, who often have inferior outcomes with immunochemotherapy.

Grade 3 or higher adverse events were reported in 48.8% of treated patients, with four individuals experiencing events that led to treatment discontinuation. Of note, serious adverse events such as atrial fibrillation and/or flutter, as well as major hemorrhage, were not reported in any participants.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.


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