Zanubrutinib Well Tolerated, Exhibits Consistent Safety Profile in Patients With B-Cell Malignancies

According to a pooled analysis of data from 6 studies, zanubrutinib monotherapy for patients with B-cell malignancies is consistent with the toxicity profile of Burton tyrosine kinase (BTK) inhibitors. Zanubrutinib also exhibited a lower incidence of atrial fibrillation and hypertension compared to reports with ibrutinib.

“The dataset is noteworthy for its geographic and ethnic diversity, variety of B-cell malignancies, proportion of patients exposed to treatment ≥ 24 months, and substantial representation of elderly (≥ 75 years) patients,” said Constantine Tam, MD, MBBS, Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues. “Results from regression analyses suggest there may be an increased risk of major hemorrhage among zanubrutinib recipients receiving concurrent antiplatelet or anticoagulant therapy but must be interpreted cautiously, given the small number of major bleeding events,” continued Dr Tam.

Researchers analyzed safety data from 779 patients who had enrolled in 6 multicenter studies, including a phase 1 dose-comparison study, a phase 1/2 dose escalation study, several phase 2 studies, and a phase 3, randomized comparative trial of ibrutinib versus zanubrutinib. Patients in the cohort received zanubrutinib at doses from 40 to 320 mg/d.

The median treatment duration was 26 months; 16% of patients were treated for 3 years or longer. The median follow-up time was 28.6 months.

Zanubrutinib was approved for medical use in the United States in November 2019. The cutoff date for the study was March 31, 2020.

About a third (33%) of patients had Waldenstrom macroglobulinemia, while 29% had either chronic lymphocytic leukemia or small lymphocytic lymphoma, and 19% had mantle cell lymphoma. Of the cohort, 21% had a history of cardiac disorder, including 7% with a history of or current atrial fibrillation. However, atrial fibrillation, hypertension, and diarrhea occurred at lower rates than those reported historically for ibrutinib.

Grade 3 or higher AEs included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%). In all, 10% discontinued treatment due to treatment-emergent adverse events (TEAEs), and 4% suffered fatal TEAEs. Major hemorrhage also occurred in 4% of patients.

Source:
Tam C, Dimopoulos M, Garcia-Sanz R, et al. Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies. Blood Adv. 2022 Feb 22;6(4):1296-1308.