Τίτλος:
Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 5 779). 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 5 9), sepsis (n 5 4), unspecified cause (n 5 4), and multiple organ dysfunction syndrome (n 5 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. © 2022 by The American Society of Hematology.
Συγγραφείς:
Tam, C.S.
Dimopoulos, M.
Garcia-Sanz, R.
Trotman, J.
Opat, S.
Roberts, A.W.
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, W.Y.
Cohen, A.
Novotny, W.
Huang, J.
Tedeschi, A.
Περιοδικό:
Blood advances
Εκδότης:
American Society of Hematology
Λέξεις-κλειδιά:
ibrutinib; zanubrutinib, age; anemia; atrial fibrillation; B cell leukemia; B cell lymphoma; bleeding; bone pain; chronic lymphatic leukemia; Conference Paper; constipation; contusion; coughing; data analysis; diarrhea; diffuse large B cell lymphoma; disease severity; drug dose reduction; drug safety; drug tolerability; drug withdrawal; dyspnea; fatigue; fever; follicular lymphoma; hairy cell leukemia; headache; heart atrium flutter; hematuria; human; hypertension; incidence; infection; lymphocytic lymphoma; mantle cell lymphoma; marginal zone lymphoma; multiple organ failure; musculoskeletal pain; myalgia; nausea; neutropenia; nonhodgkin lymphoma; opportunistic infection; pneumonia; purpura; rash; sepsis; skin cancer; thrombocytopenia; treatment duration; treatment outcome; tumor lysis syndrome; upper respiratory tract infection; urinary tract infection; vomiting; Waldenstroem macroglobulinemia
DOI:
10.1182/bloodadvances.2021005621
