Venetoclax Plus Azacitidine Shows Promising Activity Among Elderly Patients With Relapsed AML
The combination of venetoclax and azacitidine demonstrated encouraging responses with manageable toxicity among elderly patients with relapsed acute myeloid leukemia (AML), according to study results published in the Mediterranean Journal of Hematology and Infectious Diseases.
While standard therapies for AML have demonstrated efficacy and tolerability among patients, poor prognosis for those who are older or who have genetic abnormalities remain. To identify an optimized regimen, researchers conducted a single-center retrospective study to determine the efficacy and impact of venetoclax plus azacitidine for elderly or unfit patients with R/R AML.
The primary end point was overall response rate (ORR) among patients 65 years or older with relapsed AML and secondary endpoints included overall survival (OS), event-free survival (EFS), and safety.
Overall, 50 patients were included, and the median age was 72 (range, 65 to 82). Among patients, 44% presented intermediate features, 46% presented cytogenetic features, and 16% were positive for a FLT3-ITD mutation. Most patients had at least one prior line of therapy (40%) and 24% had at least 3 prior lines of therapy. Prior allogeneic hematopoietic stem cell transplantation (alloHSCT) was reported by 14%.
The ORR was 60%, including 40% complete remission (CR) rate and 20% CR with incomplete hematologic recovery (CRi). A partial remission was met by 10% of patients. The median OS was 9.2 months (95% confidence interval [CI], 6.8 to 11.5), and the median EFS was 6.0 months (95% CI, 4.2 to 8.3).
Results from a univariate Cox analysis found poorer OS to be associated with ECOG performance status ≥2 (hazard ratio [HR], 2.1; 95% CI, 1.2 to 3.4; P = .002), adverse cytogenetics (HR, 1.8; 95% CI, 1.1 to 3.0; P = .015), and high baseline lactate dehydrogenase (LDH) levels (HR, 1.6; 95% CI, 1.0 to 2.6; P = .048).
In terms of safety, grade 3–4 neutropenia occurred among 46% and thrombocytopenia occurred in 32% of patients. Infections occurred in 36% of patients, while 24% had febrile neutropenia.
The researchers concluded, “Venetoclax combined with azacitidine demonstrated encouraging efficacy and manageable toxicity in this retrospective analysis of elderly patients with relapsed AML. Our real-world, single-center experience provides practical insights for a vulnerable, often underrepresented elderly AML population, and our biomarker analysis adds novelty to the existing literature.”
They added, “Future work should involve larger, prospective, or multicenter studies to validate these results, explore novel therapeutic combinations and more robust biomarker profiling, and ultimately advance personalized medicine strategies to optimize treatment outcomes.”
Source:
Yan M, Wang G, Wang J. Efficacy of venetoclax combined with azacitidine in elderly patients with relapsed acute myeloid leukemia. Mediterranean Journal of Hematology and Infectious Diseases. Published online September 1, 2025. doi:10.4084/mjhid.2025.058
