Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies

Tam, CS; Dimopoulos, M; Garcia-Sanz, R; Trotman, J; Opat, S; Roberts, AW; Owen, R; Song, Y; Xu, W; Zhu, J; Li, J; Qiu, L; D&#39;Sa, S; Jurczak, W; Cull, G; Marlton, P; Gottlieb, D; Munoz, J; Phillips, T; Du, C; Ji, M; Zhou, L; Guo, H; Zhu, H; Chan, WY; Cohen, A; Novotny, W; Huang, J; Tedeschi, A

Author(s): Tam, CS; Dimopoulos, M; Garcia-Sanz, R; Trotman, J; Opat, S; Roberts, AW; Owen, R; Song, Y; Xu, W; Zhu, J; Li, J; Qiu, L; D'Sa, S; Jurczak, W; Cull, G; Marlton, P; Gottlieb, D; Munoz, J; Phillips, T; Du, C; Ji, M; Zhou, L; Guo, H; Zhu, H; Chan, WY; Cohen, A; Novotny, W; Huang, J; Tedeschi, A;
Details: Publication Year 2022-02,Volume 6,Issue #4,Page 1296-1308
Journal Title: Blood Advances
Publication Type: Research article
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 Waldenstrom 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 (21%), pneumonia (21%), urinary tract infection (UTI), and 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 adverse events included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%).Treatment discontinuations and dose reductions for adverse events 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.
Keywords: Adult; Aged; *Atrial Fibrillation; Diarrhea/chemically induced; Humans; *Hypertension; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy; *Lymphoma, B-Cell; *Lymphoma, Follicular; *Musculoskeletal Pain; Piperidines; *Pneumonia; Pyrazoles; Pyrimidines; *Sepsis
Department(s): Haematology
PubMed ID: 34724705
Publisher's Version: https://doi.org/10.1182/bloodadvances.2021005621
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2021005621
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-04-11 08:06:34

Last Modified: 2025-04-11 08:08:00