Venetoclax-Based Regimens Show Promising Efficacy, Safety Profile for Older Patients with AML

A recent meta-analysis showed that venetoclax combined with low-intensity therapies like hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) were efficacious and had a reasonable safety profile in older patients with acute myeloid leukemia (AML).

“The prognosis for older patients with AML remains poor due to the aggressive nature of the disease and the limitations of conventional chemotherapy, which is often not well tolerated in this population,” the authors wrote.

Importantly, venetoclax, a BCL2 inhibitor, is considered a promising treatment option when combined with HMA or LDAC. But to determine the safety, efficacy, and predictive factors for response to venetoclax-based regimens in older patients with AML, researchers developed a meta-analysis of 12 studies, including 1432 older patients with AML treated with venetoclax-based regimens.

Qureshi and colleagues conducted a comprehensive search using PubMed, Embase, Web of Science, and Google Scholar databases. For statistical analyses, they used Review Manager or the Comprehensive Meta-Analysis software. Their bias assessment of the included randomized studies was performed with Cochrane’s risk of bias tool.

The pooled analysis showed that, among patients treated with venetoclax and HMAs, the rate of complete response with or without incomplete blood count recovery (CR/CRi) was 59% and the overall response rate (ORR) was 64%. For patients treated with venetoclax and LDAC, an ORR of 50% was observed.

Venetoclax combined with HMAs showed a significant survival benefit (HR = 0.57; [95% CI, 0.47 to 0.68]; P < 0.00001). Looking at the safety profile of these regimens, the most common grade 3 or greater hematologic disorder in patients with AML treated with venetoclax and HMAs was febrile neutropenia (39%). For patients treated with venetoclax and LDAC, thrombocytopenia was more common (41%).

“Venetoclax combined with HMAs or LDAC demonstrated promising efficacy and a tolerable safety profile in older patients with AML,” the researchers concluded. “Moreover, venetoclax and HMAs showed significant survival benefits among older patients with AML. TP53 and FLT3 mutations, R/R AML, and adverse cytogenetics predicted poor response rates in patients treated with venetoclax combined with HMAs.”

Reference
Qureshi Z, Jamil A, Altaf F, Siddique R. Safety, efficacy, and predictive factors of venetoclax-based regimens in older patients with acute myeloid leukemia: a meta-analysis. In: Proceedings of the Society of Hematologic Oncology 2024 Annual Meeting. Clin Lymphoma Myeloma Leuk. 2024 Sept;9(24);Supplement 1:S331.