Low-Dose Venetoclax with Azacitidine Shows Rapid Remissions in Unfit Elderly AML

Elderly patients newly diagnosed with acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy may benefit from a deliberately reduced-dose combination of azacitidine and venetoclax, according to a retrospective analysis published in Clinical and Experimental Medicine. In the single-center study, 32 unfit elderly patients treated between January 2021 and March 2025 received subcutaneous azacitidine at 75 mg/m² daily on days 1–5 together with oral venetoclax at just 100 mg daily, initially given on days 3–16 of each cycle.

The defining feature of the regimen was its response-adapted venetoclax dosing, adjusted dynamically according to the bone marrow blast burden measured on day 17. When blasts remained at 10% or higher, venetoclax was prolonged to day 28. When blasts fell below 10%, the drug was discontinued in patients with hypoplastic marrow but extended to day 28 in those with normocellular marrow.

The reported remission outcomes were substantial. After the first induction cycle, the composite complete remission rate, combining complete remission and complete remission with incomplete hematologic recovery, reached 81.3%, with 43.8% of patients achieving minimal residual disease negativity. By cycle 2, the composite complete remission rate rose to 84.4% and MRD negativity to 65.6%, and the cumulative induction composite complete remission rate reached 87.5%. Median follow-up was 7.3 months, during which median overall survival was 12.3 months and median progression-free survival was 10.1 months.

Safety findings were presented as controllable within this unfit population. Grade 3 or higher thrombocytopenia occurred in 37.5% of patients, and febrile neutropenia in 43.8%. Thirty-day mortality was 0%, while 60-day mortality stood at 6.3%. Notably, the authors report that 40.6% of patients avoided platelet transfusion during induction, including some with baseline platelet counts as low as 29 × 10⁹/L who received no prophylactic interventions. The team interprets this reduced transfusion reliance as a marker of superior tolerability compared with standard-intensity approaches, although the study design did not include a direct comparison group.

The authors conclude that this response-adapted reduced-dose azacitidine-venetoclax regimen achieves rapid, deep remission with acceptable safety and serves as a feasible individualized treatment strategy for this high-risk elderly cohort. The findings carry important caveats: the analysis was retrospective, involved a single center and only 32 patients, and the relatively short median follow-up of 7.3 months limits conclusions about long-term survival. As an early-access, peer-reviewed accepted manuscript, the article is also subject to further editorial revision before the final version of record.

Subject of Research: A reduced-dose, response-adapted azacitidine plus venetoclax regimen for elderly newly diagnosed unfit acute myeloid leukemia patients

Article Title: Azacitidine plus low-dose venetoclax in elderly newly-diagnosed unfit AML: efficacy, safety, and implications for dose optimization

Article References: Zhou, Z., Lou, H., Luo, Y., Jiang, Y., Weng, Y., Rong, C., Yang, F., Chen, Y., Ai, C., Gao, P., Qian, J., Shi, J., Huang, X., Zhang, X., Qian, W., Duan, S., & Xia, Y. (2026). Azacitidine plus low-dose venetoclax in elderly newly-diagnosed unfit AML: efficacy, safety, and implications for dose optimization. Clinical and Experimental Medicine. https://doi.org/10.1007/s10238-026-02366-2

Image Credits: AI Generated

DOI: 10.1007/s10238-026-02366-2

Keywords: acute myeloid leukemia, azacitidine, venetoclax, elderly patients, dose optimization, remission, MRD negativity, hematologic toxicity, transfusion avoidance, retrospective study, plus, low-dose