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

Zeidan, AM; Borate, U; Pollyea, DA; Brunner, AM; Roncolato, F; Garcia, JS; Filshie, R; Odenike, O; Watson, AM; Krishnadasan, R; Bajel, A; Naqvi, K; Zha, J; Cheng, WH; Zhou, Y; Hoffman, D; Harb, JG; Potluri, J; Garcia-Manero, G

Author(s): Zeidan, AM; Borate, U; Pollyea, DA; Brunner, AM; Roncolato, F; Garcia, JS; Filshie, R; Odenike, O; Watson, AM; Krishnadasan, R; Bajel, A; Naqvi, K; Zha, J; Cheng, WH; Zhou, Y; Hoffman, D; Harb, JG; Potluri, J; Garcia-Manero, G;
Details: Publication Year 2023-02,Volume 98,Issue #2,Page 272-281
Journal Title: American Journal of Hematology
Publication Type: Research article
Abstract: 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.
Publisher: Wiley
Keywords: Aged; Humans; Male; *Antineoplastic Combined Chemotherapy Protocols/adverse effects; Azacitidine/therapeutic use; Leukemia, Myeloid, Acute/drug therapy; *Myelodysplastic Syndromes/drug therapy; Neutropenia/chemically induced; Sulfonamides; Treatment Outcome; Female
Department(s): Clinical Haematology
PubMed ID: 36309981
Publisher's Version: https://doi.org/10.1002/ajh.26771
Open Access at Publisher's Site: https://doi.org/10.1002/ajh.26771
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-06-15 07:25:01

Last Modified: 2023-06-15 07:25:48