Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia

Abstract

The combination of a hypomethylating agent (HMA) and venetoclax (VEN) is approved for adults aged >75 years with newly diagnosed acute myeloid leukemia (AML) as well as those ineligible for intensive chemotherapy (IC). HMA/VEN is increasingly substituted for IC in adults with AML aged <75 years, particularly in those with adverse cytogenetic and molecular features. When patients fail to respond or relapse after HMA/VEN, the utility of salvage IC is largely unknown. We performed a retrospective single-institution study and identified 46 patients who received IC after HMA/VEN, including 24 patients who received HMA/VEN as their first treatment for AML. This population had complete remission (CR)/CR with incomplete count recovery (CRi)/morphologic leukemia-free state rate of 37%, CR/CRi rate of 28%, and a median overall survival (mOS) of 7.2 months (95% confidence interval, 5.0-10.3). Patients who relapsed after an initial response to HMA/VEN and subsequently received IC were more likely to achieve a CR/CRi than those refractory to HMA/VEN (50% vs 19%; P = .04), although there was no statistically significant difference in survival (mOS, 8.8 vs 5.4 months; P = .64). Age >65 years predicted poorer survival (mOS, 4.3 vs 10.6 months; P < .001). IC after HMA/VEN should be further studied and chosen with caution.