Venetoclax Plus Azacitidine Achieves High Response Rates in Untreated High-Risk MDS

By Patrick Daly - Last Updated: December 5, 2023

Venetoclax plus azacitidine was well tolerated and achieved favorable rates of complete response (CR), partial response (PR), and marrow CR (mCR) in a majority of patients with treatment-naïve higher-risk myelodysplastic syndromes (MDS), reported authors of a phase Ib study presented at the 65th American Society of Hematology Annual Meeting and Exposition in San Diego, California.

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Lead and presenting author, Jacqueline Garcia, MD, of the Dana-Farber Cancer Institute at Harvard Medical School in Boston, Massachusetts, also stated that venetoclax plus azacitidine induced hematologic improvements in half of the study’s patient population.

Dr. Garcia’s presentation covered 107 participants with higher-risk MDS defined by a Revised International Prognostic Scoring System score greater than three, an Eastern Cooperative Oncology Group performance status of two or less, and less than 20% bone marrow blasts at baseline. The cohort had a median age of 68 years (range, 26-87), 64% of patients had intermediate or poor cytogenetic risk, and 89% of patients had at least five percent bone marrow blasts.

All patients received the recommended phase II dose of oral venetoclax 400 mg once daily on days one through 14 alongside intravenous or subcutaneous azacitidine 75 mg/m2 on days one through seven or days one through five eight, and nine over 28-day cycles.

The primary endpoint was the rate of CR, and major secondary endpoints included duration of CR, mCR, hematologic improvement, overall response rate (ORR), red blood cell and platelet transfusion independence, overall survival (OS), time to next treatment, transformation to acute myeloid leukemia (AML), and time until AML transformation.

At the data cutoff of May 31, 2023, the cohort had a median OS of 26 months (95% CI, 18.1-51.5) and estimated 12-month and 24-month OS rates of 71.2% (95% CI, 61.4-78.9) and 51.3% (95% CI, 41.2-60.5), respectively. Hematologic improvements were observed in 51 out of 104 (49%) evaluable patients; specifically, erythroid response in 40 out of 93 (43%), platelet response in 32 out of 74 (43.2%), and neutrophil response in 10 out of 57 (17.5%).

The median time to next treatment was 6.8 months (95% CI, 5.6-8.3) in the 57.9% of patients who underwent further therapies, of which 39.3% included transplantation. The median time to transplantation was 4.8 months (range ,1.4-16.8). The authors noted that 17 patients who received transplantations were not eligible for transplantation at the study baseline.

While the majority of patients reported grade 3 or higher treatment-emergent adverse events, Dr. Garcia and colleagues supported the favorable response rates, and noted that “a separate phase III study of this combination is ongoing to confirm survival benefit.”

Reference

Garcia JS, Platzbecker U, Odenike O, et al. Efficacy and safety of venetoclax in combination with azacitidine for the treatment of patients with treatment-naive, higher-risk myelodysplastic syndromes. Abstract #319. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.

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