Treatment with zanubrutinib was well tolerated and associated with high clinical activity in patients with relapsed/refractory (R/R) Waldenstrom macroglobulinemia (WM), according to a phase II study presented by Gang An, MD, of the Blood Diseases Hospital in China, at the 62nd American Society of Hematology Annual Meeting & Exposition.
The study was conducted in China and included 44 patients with R/R WM who were treated with one or more prior line of standard chemotherapy-containing regimens. Patients received zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity.
Efficacy was assessed by the major response rate (MRR), which was defined as the percentage of patients who achieved a complete response, very-good partial response (VGPR), or partial response. Progression-free survival (PFS), overall response rate, duration of major response, and safety comprised the secondary endpoints.
The median follow-up was 18.58 months. The MRR in the 43 patients evaluable for efficacy was 69.8%, with 32.6% of patients achieving a VGPR or better. The median PFS and median duration of response were not reached by the time of data cutoff.
Treatment-emergent adverse events (AEs) reported in 20% or more of patients were reduced neutrophil counts (56.8%), reductions in platelet counts (29.5%), decreased white blood cell counts (27.3%), upper respiratory tract infection (27.3%), diarrhea (25.0%), increased weight (20.5%), and arthralgia (20.5%).
In addition, grade 3 or higher AEs reported in 5% or more of patients included decreased neutrophil counts (31.8%), decreased platelet counts (20.5%), lung infection (13.6%), decreased white blood cell count (11.4%), pneumonia (9.1%), anemia (6.8%), and upper respiratory tract infection (6.8%).
There were no reported cases of atrial fibrillation/flutter or tumor lysis syndrome. Two patients died within a 30-day period from the last study treatment. Deaths were due to acute hepatitis B and multiple organ dysfunction syndrome (n=1), which were related to the study drug, and an unknown reason unlikely related to the treatment drug (n=1).
The treatment-related AEs that led to zanubrutinib discontinuation included lung infection (n=1), laryngeal cancer (n=1), WM (n=1), intracranial mass (n=1), acute hepatitis B (n=1), and multiple organ dysfunction syndrome (n=1).