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Combination of Zandelisib Plus Zanubrutinib in Treatment of B-Cell Malignancies

By: Kayci Reyer
Posted: Friday, January 20, 2023

According to research presented at the 2022 Annual Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 78), a combination treatment of zandelisib plus zanubrutinib appears to be a safe and potentially active treatment for some patients with B-cell malignancies. Treatment with zandelisib and zanubrutinib, respectively P13Kδ and Bruton’s tyrosine kinase inhibitors, may help patients with relapsed or refractory follicular or mantle cell lymphoma overcome single-agent treatment resistance.

“Zandelisib plus zanubrutinib was well tolerated, with no increase in the rate or severity of class-related adverse events compared to either agent alone,” concluded Jacob D. Soumerai, MD, of Massachusetts General Hospital, Boston, and colleagues. “Additionally, responses appear to deepen over time.”

The study included 50 patients, 31 with follicular lymphoma and 19 with mantle cell lymphoma. Patients received 60 mg of zandelisib via intermittent dosing during the first 7 days of a 28-day treatment cycle plus 80 mg of twice-daily zanubrutinib. Treatment continued until disease progression or intolerance occurred. At follow-up on June 23, the median time receiving combination treatment for the 30 patients still on therapy was 11.4 months in the follicular lymphoma group and 6.5 months in the mantle cell lymphoma group. At that follow-up, 20 patients had discontinued treatment due to progressive disease (30%), consent withdrawal (6%), or adverse events (4%).

The overall response and complete response rates were, respectively, 80% and 20% in the follicular lymphoma group and 76% and 35% in the mantle cell lymphoma group. At a median follow-up of 11.1 months, median progression-free survival was 22.4 months in the follicular lymphoma group; at a median follow-up of 10.8 months, median progression-free survival was 10.4 months in the mantle cell lymphoma group. Significant adverse events included grade 3 atrial fibrillation, pneumonia, febrile neutropenia, and sepsis and grade 4 drug reaction with eosinophilia and systemic symptoms syndrome.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.


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