On August 31, 2021, the FDA approved zanubrutinib (Brukinsa; BeiGene), a Bruton tyrosine kinase (BTK) inhibitor, for the treatment of adults with Waldenström’s macroglobulinemia. Zanubrutinib was previously approved for the treatment of adults with mantle-cell lymphoma.
“The ASPEN trial provided compelling evidence that Brukinsa is a highly active BTK inhibitor in Waldenström’s macroglobulinemia, and compared to the first-generation BTK inhibitor, showed improved tolerability across a number of clinically important side effects,” Steven Treon, MD, PhD, Director, Bing Center for Waldenström’s Macroglobulinemia Research, Dana-Farber Cancer Institute, Boston, MA, and Professor, Medicine, Harvard Medical School, Boston, said in a statement. “The approval of Brukinsa provides an important new option for targeted therapy in Waldenström’s macroglobulinemia.”
The FDA approved zanubrutinib for this indication based on results from the open-label, phase 3 ASPEN clinical trial comparing zanubrutinib with ibrutinib (Imbruvica; Pharmacyclics) in patients with Waldenström’s macroglobulinemia and a MYD88L265P mutation. A total of 201 patients were enrolled in the randomized cohort 1 of the study. The primary end point was very good partial response in the intent-to-treat population. Using the modified Sixth International Workshop on Waldenström’s Macroglobulinemia criteria, the response rate of partial response or better was 77.5% for zanubrutinib versus 77.8% for ibrutinib. At 12 months, the event-free DOR was 94.4% for zanubrutinib compared with 87.9% for ibrutinib.
The most common (≥20%) adverse reactions were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
