Which Factors Impact Hematological Recovery After Venetoclax in AML, MDS-IB?

In patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes with increased blasts (MDS-IB) who received treatment with venetoclax and hypomethylating agents (HMAs), factors such as length of venetoclax dosing and prior chemotherapy exposure were associated with prolonged hematological recovery, according to a study presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

The investigators conducted a single-center retrospective study of 58 patients with newly diagnosed AML (n=49) or MDS-IB (n=9) who achieved a complete response (CR), CR with incomplete hematological recovery (CRi), or morphological leukemia-free state (MLFS) after receiving venetoclax plus HMA. The median patient age was 70.5 years. The primary endpoint was time to absolute neutrophil count (ANC) >1,000 cells/mm³ and platelet (PLT) count >100,000 cells/mm³ recovery, along with factors associated with myelosuppression.

Patients were divided according to ANC and PLT recovery time, starting from day one of the treatment cycle inducing the best response. The “early recovery” cohort was defined as patients who recovered in fewer than 35 days (ANC group, n=19; PLT group, n=27). The “prolonged recovery” group comprised patients who recovered in 35 or more days or who did not recover (ANC group, n=39; PLT group, n=31).

Overall, 82.2% of patients achieved CR or CRi, and 17.2% had MLFS lacking hematological recovery. RUNX1 was the most common mutation (22.4%), followed by TP53 (20.7%) and FLT3 (19%). However, these mutations were not significantly associated with prolonged neutropenia.

Longer recovery was associated with prior chemotherapy (P=0.023). Venetoclax dosing for longer than 14 days was associated with prolonged ANC recovery (P=0.044). Overall survival was 12 months in the early (95% CI, N/A) and nine months in the prolonged (95% CI, 5.7-12.3) ANC recovery groups, which was not significantly different. Patients with baseline ANC levels of at least 1,000 cells/mm³ had longer PLT recovery (P=0.021). Additionally, patients with a prior MDS or myeloproliferative neoplasm (MPN) diagnosis also had longer PLT recovery (P=0.001)

“Prior chemotherapy exposure and venetoclax dosing for >14 days are associated with prolonged ANC recovery, whereas prior MDS/MPN diagnosis and a higher baseline ANC level resulted in longer PLT recovery after [venetoclax plus] HMA therapy,” the authors summarized.

Reference

Smalinskaitė T, Kevličius L, Vaitekėnaitė V, et al. Prolonged cytopenias after first line treatment with venetoclax and hypomethylating agent in newly diagnosed AML/MDS-IB. Abstract #AML-700. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; Sept. 4-7, 2024; Houston, Texas.