What question did this study set out to answer?

To evaluate the efficacy and safety of venetoclax combined with hypomethylating agents in treatment-naïve patients with myelodysplastic syndromes with increased blasts.

April 26, 2026Open Access

Venetoclax Plus Hypomethylating Agents for Treatment-Naïve Myelodysplastic Syndromes with Increased Blasts: A Prospective Multicenter Cohort Study

NZNa ZhaoUniversity of Science and Technology of China LZLijun ZhuUniversity of Science and Technology of China XHXing HuUniversity of Science and Technology of China

Key Points

To evaluate the efficacy and safety of venetoclax combined with hypomethylating agents in treatment-naïve patients with myelodysplastic syndromes with increased blasts.
Conducted as a single-arm trial across six hospitals in China from August 2022 to September 2024.
Forty-three newly diagnosed adults received venetoclax plus azacitidine or decitabine in 28-day cycles with dose adjustments for toxicity.
Primary endpoints included overall response rate, duration of response, and safety, with secondary endpoints focusing on overall survival.
Overall response rate was 74.4% (95% CI, 58.8-86.5%), with 34.4% achieving complete remission.
Median duration of response was 8.1 months, with 68.8% maintaining response at 6 months.
Median overall survival was 12.8 months, with 62.4% surviving at 12 months.

Abstract

Purpose: Evidence supporting venetoclax combined with hypomethylating agents (HMAs) in treatment-naïve myelodysplastic syndromes with increased blasts (MDS-IB), a biologically aggressive subset with high risk of leukemic transformation, remains lacking. We conducted a prospective, multicenter cohort study to evaluate the efficacy and safety of venetoclax plus HMAs in newly diagnosed MDS-IB. Patients and Methods: In this prospective, multicenter, single-arm trial conducted at six hospitals in China (August 2022–September 2024), 43 newly diagnosed adults with MDS-IB received venetoclax (ramp-up to 400 mg on days 1– 14) plus azacitidine or decitabine in 28-day cycles. Dose adjustments were made for cytopenias, infections, or drug interactions. Primary endpoints were overall response rate (ORR), duration of response (DoR), and safety. Secondary endpoints included overall survival (OS) and transformation to acute myeloid leukemia. The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200055204). Results: The ORR was 74.4% (95% CI, 58.8-86.5%), comprising 34.4% complete remission (CR), 59.4% marrow CR (mCR), and 6.3% partial response (PR). Among the thirty-two patients who got ORR, the median DoR was 8.1 months (range, 0.9– 29.0). The 6-, 12-, and 24-month DoR rates were 68.8% (95% CI, 49.7– 81.8%), 53.2% (95% CI, 33.7– 69.4%), and 47.7% (95% CI, 27.8– 65.1%), respectively. Median OS was 12.8 months, with 12- and 24-month OS rates of 62.4% (95% CI, 46.1– 75.1%) and 49.3% (95% CI, 32.2– 64.3%), respectively. Grade 3/4 neutropenia/febrile neutropenia occurred in 60% (26/43), and pneumonia in 16% (7/43). The median interval between cycles was 59 days (range 33– 113), mainly due to hematologic toxicity. Conclusion: Venetoclax plus HMAs demonstrated promising clinical activity with manageable toxicity in newly diagnosed MDS-IB, supporting further prospective evaluation of this combination in treatment-naïve patients with increased-blast MDS. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200055204, https://www.chictr.org.cn/index.html . Keywords: venetoclax, hypomethylating agents, myelodysplastic syndromes

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