Venetoclax Plus Hypomethylating Agents for Treatment-Naïve Myelodysplastic Syndromes with Increased Blasts: A...

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.

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]).

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.

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.

Chinese Clinical Trial Registry, ChiCTR2200055204, https://www.chictr.org.cn/index.html.