TY - JOUR
T1 - A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes
AU - Zeidan, Amer M.
AU - Borate, Uma
AU - Pollyea, Daniel A.
AU - Brunner, Andrew M.
AU - Roncolato, Fernando
AU - Garcia, Jacqueline S.
AU - Filshie, Robin
AU - Odenike, Olatoyosi
AU - Watson, Anne Marie
AU - Krishnadasan, Ravitharan
AU - Bajel, Ashish
AU - Naqvi, Kiran
AU - Zha, Jiuhong
AU - Cheng, Wei Han
AU - Zhou, Ying
AU - Hoffman, David
AU - Harb, Jason G.
AU - Potluri, Jalaja
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2023/2
Y1 - 2023/2
N2 - 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/m2/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.
AB - 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/m2/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.
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U2 - 10.1002/ajh.26771
DO - 10.1002/ajh.26771
M3 - Article
C2 - 36309981
AN - SCOPUS:85141952850
SN - 0361-8609
VL - 98
SP - 272
EP - 281
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 2
ER -