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

Amer M. Zeidan, Uma Borate, Daniel A. Pollyea, Andrew M. Brunner, Fernando Roncolato, Jacqueline S. Garcia, Robin Filshie, Olatoyosi Odenike, Anne Marie Watson, Ravitharan Krishnadasan, Ashish Bajel, Kiran Naqvi, Jiuhong Zha, Wei Han Cheng, Ying Zhou, David Hoffman, Jason G. Harb, Jalaja Potluri, Guillermo Garcia-Manero

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)272-281
Number of pages10
JournalAmerican Journal of Hematology
Issue number2
StatePublished - Feb 2023
Externally publishedYes

ASJC Scopus subject areas

  • Hematology


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