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Venetoclax Plus Azacitidine Shows ‘Encouraging OS’ in R/R MDS with Prior HMA Failure

By  Leah Sherwood - Last Updated: January 19, 2023

Venetoclax plus azacitidine provided “clinically meaningful benefits” in patients with relapsed or refractory (R/R) myelodysplastic syndromes (MDS) who had failed prior treatment with a hypomethylating agent (HMA), according to results of a phase Ib study.


The study, led by Amer M. Zeidan, MD, of the hematology section in the Department of Internal Medicine at Yale University and Yale Cancer Center in New Haven, Connecticut, evaluated the safety of venetoclax either alone or in combination with azacitidine therapy after HMA failure.

The investigators noted that there is “no standard of care for patients after HMA therapy failure; hence, there is a critical need for effective therapeutic strategies.”

The open-label, multicenter study consisted of three cohorts: (1) venetoclax monotherapy; (2) escalating doses of venetoclax (100, 200, and 400 mg) in combination with azacitidine to evaluate the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD); and (3) safety and efficacy of venetoclax 400 mg with azacitidine.

At the data cutoff date, 44 patients were enrolled in the venetoclax and azacitidine cohorts. Due to limited efficacy, the venetoclax monotherapy regimen was discontinued. The median follow-up of the study was 21.2 months (range, 0.4-37.5 months). The median age of patients treated with venetoclax and azacitidine was 74 years (range, 44-91 years), and the median number of prior HMA therapies was one (range, 1-2 therapies), with 28 (65%) patients receiving six or more cycles of therapy.

Grade ≥3 hematological adverse events included febrile neutropenia (34%), thrombocytopenia (32%), neutropenia (27%), and anemia (18%).

In the 44 patients who were enrolled in the venetoclax and azacitidine cohorts, marrow responses were seen, including complete remission (CR; n=3; 7%) and marrow CR (mCR; n=14; 32%); 36% (n=16/44) achieved transfusion independence for red blood counts and/or platelets, and 43% (n=6/14) with mCR achieved hematological improvement. The median time to CR/mCR was 1.2 months, and the median duration of response for CR plus mCR was 8.6 months. Median overall survival (OS) was 12.6 months.

No DLTs were reported in the dose-escalation cohorts, and the MTD was not reached in any cohort.

“The study demonstrated a manageable safety profile with meaningful clinical benefits with the combination of venetoclax and azacitidine in adult patients with R/R MDS,” Dr. Zeidan and colleagues wrote, noting that the combination “provides clinically meaningful benefits, including [hematologic improvement] and [transfusion independence] and encouraging OS.”

This study was funded by AbbVie and Genentech.


Zeidan AM, Borate U, Pollyea DA, et al. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Am J Hematol. 2023;98(2):272-281.

Original Source: Venetoclax Plus Azacitidine Shows ‘Encouraging OS’ in R/R MDS with Prior HMA Failure | Blood Cancers Today

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