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

• After HMA/VEN treatment, AML patients treated with IC had a CR/CRi rate of 28% and median overall survival of 7.2 months.

• Patients over 65 did poorly with IC after HMA/VEN, achieving a median overall survival of 4.3 months (vs 10.6 months for younger patients)

The combination of a hypomethylating agent (HMA) and venetoclax (VEN) is approved for adults older than 75-years-old 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 younger than 75, 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 CR/CRi/MLFS rate of 37%, CR/CRi rate of 28% and median overall survival (OS) of 7.2 months (95% CI 5.0, 10.3 months). 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 = 0.04), though there was no statistically significant difference in survival (mOS 8.8 vs 5.4 months, p = 0.64). Age over 65 predicted poorer survival (mOS 4.3 vs 10.6 months, p < 0.001). IC after HMA/VEN should be further studied and chosen with caution.