A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes.

Autor: Zeidan AM; Section of Hematology, Department of Internal Medicine, Yale University and Yale Cancer Center, New Haven, Connecticut, USA., Borate U; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA., Pollyea DA; Division of Hematology, Department of Medicine, University of Colorado, Aurora, Colorado, USA., Brunner AM; Center for Leukemia, Massachusetts General Hospital, Boston, Massachusetts, USA., Roncolato F; Department of Hematology, St George Hospital, Sydney, New South Wales, Australia., Garcia JS; Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Filshie R; Department of Hematology, St Vincent's Hospital, Melbourne, Victoria, Australia., Odenike O; Section of Hematology/Oncology, University of Chicago Medicine and Comprehensive Cancer Center, Chicago, Illinois, USA., Watson AM; Department of Hematology, Liverpool Hospital, Sydney, New South Wales, Australia., Krishnadasan R; Department of Hematology, University of Arizona Cancer Center, Tucson, Arizona, USA., Bajel A; Department of Clinical Hematology, Peter MacCallum Cancer Center and The Royal Melbourne Hospital, Melbourne, Victoria, Australia., Naqvi K; Research and Development, Genentech Inc, South San Francisco, California, USA., Zha J; Research and Development, AbbVie Inc, North Chicago, Illinois, USA., Cheng WH; Research and Development, AbbVie Inc, North Chicago, Illinois, USA., Zhou Y; Research and Development, AbbVie Inc, North Chicago, Illinois, USA., Hoffman D; Research and Development, AbbVie Inc, North Chicago, Illinois, USA., Harb JG; Research and Development, AbbVie Inc, North Chicago, Illinois, USA., Potluri J; Research and Development, AbbVie Inc, North Chicago, Illinois, USA., Garcia-Manero G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2023 Feb; Vol. 98 (2), pp. 272-281. Date of Electronic Publication: 2022 Nov 10.
DOI: 10.1002/ajh.26771
Abstrakt: Patients with relapsed/refractory (R/R) higher-risk myelodysplastic syndromes (MDS) have a dismal median overall survival (OS) after failing hypomethylating agent (HMA) treatment. There is no standard of care for patients after HMA therapy failure; hence, there is a critical need for effective therapeutic strategies. Herein, we present the safety and efficacy of venetoclax + azacitidine in patients with R/R MDS. This phase 1b, open-label, multicenter study enrolled patients ≥18 years. Patients were treated with escalating doses of oral venetoclax: 100, 200, or 400 mg daily for 14 days every 28-day cycle. Azacitidine was administered on Days 1-7 every cycle at 75 mg/m 2 /day intravenously/subcutaneously. Responses were assessed per modified 2006 International Working Group (IWG) criteria. Forty-four patients (male 86%, median age 74 years) received venetoclax + azacitidine treatment. Median follow-up was 21.2 months. Hematological adverse events of Grade ≥ 3 included febrile neutropenia (34%), thrombocytopenia (32%), neutropenia (27%), and anemia (18%). Pneumonia (23%) was the most common Grade ≥ 3 infection. Marrow responses were seen including complete remission (CR, n = 3, 7%) and marrow CR (mCR, n = 14, 32%); 36% (16/44) achieved transfusion independence (TI) for RBCs and/or platelets, and 43% (6/14) with mCR achieved hematological improvement (HI). The median time to CR/mCR was 1.2 months, and the median duration of response for CR + mCR was 8.6 months. Median OS was 12.6 months. Venetoclax + azacitidine shows activity in patients with R/R MDS following prior HMA therapy failure and provides clinically meaningful benefits, including HI and TI, and encouraging OS.
(© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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