Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies
- Author(s)
- Tam, CS; Dimopoulos, MA; Garcia-Sanz, R; Trotman, J; Opat, S; Roberts, AW; Owen, RG; Song, Y; Xu, W; Zhu, J; Li, J; Qiu, L; D'Sa, S; Jurczak, W; Cull, G; Marlton, P; Gottlieb, DJ; Munoz, J; Phillips, T; Du, C; Ji, M; Zhou, L; Guo, H; Zhu, H; Chan, WY; Cohen, A; Novotny, W; Huang, J; Tedeschi, A;
- Journal Title
- Blood Advances
- Publication Type
- epub ahead of print
- Abstract
- Zanubrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor evaluated in multiple B-cell malignancy studies. We constructed a pooled safety analysis to better understand zanubrutinib-associated treatment-emergent adverse events (TEAEs) and identify treatment-limiting toxicities. Data were pooled from 6 studies (N=779). Assessments included type, incidence, severity, and outcome of TEAEs. Median age was 65 years; 20% were ≥75 years old. Most patients had Waldenström macroglobulinemia (33%), chronic lymphocytic leukemia/small lymphocytic lymphoma (29%), or mantle-cell lymphoma (19%). Median treatment duration was 26 months (range: 0.1-65); 16% of patients were treated for ≥3 years. Common nonhematologic TEAEs were upper respiratory tract infection (URI, 39%), rash (27%), bruising (25%), musculoskeletal pain (24%), diarrhea (23%), cough, pneumonia (21% each), urinary tract infection (UTI), fatigue (15% each). Most common grade ≥3 TEAEs were pneumonia (11%), hypertension (5%), URI, UTI, sepsis, diarrhea, and musculoskeletal pain (2% each). Atrial fibrillation and major hemorrhage occurred in 3% and 4% of patients, respectively. Atrial fibrillation, hypertension and diarrhea occurred at lower rates than those reported historically for ibrutinib. Grade ≥3 AEs included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%). Treatment discontinuations and dose reductions for AEs occurred in 10% and 8% of patients, respectively. Thirty-nine patients (4%) had fatal TEAEs, including pneumonia (n=9), sepsis (n=4), unspecified cause (n=4), and multiple organ dysfunction syndrome (n=5). This analysis demonstrates that zanubrutinib is generally well tolerated with a safety profile consistent with known BTK inhibitor toxicities; these were manageable and mostly reversible.
- Publisher
- ASH
- Research Division(s)
- Blood Cells And Blood Cancer
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2021005621
- Open Access at Publisher's Site
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Creation Date: 2021-11-09 10:48:11
Last Modified: 2021-11-09 11:04:24