Real-world evidence on the use of lower-intensity treatment with venetoclax and azacitidine in newly diagnosed AML in younger patients

Azacitidine plus venetoclax (VenAza) is approved for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). The ELN2022 risk classification identifies IC-eligible patients with markers of poor response to induction treatment, who are therefore unlikely to benefit from IC; these markers do not affect response to VenAza, which could thus be an option for non-favorable risk IC-eligible patients. We describe the real-world outcomes of 53 newly diagnosed AML patients with a median age of 65.8 years (75.5% of whom adverse risk) undergoing first-line treatment with VenAza due to either IC-ineligibility or IC-eligibility with a low likelihood of benefit. After a median follow-up of 17.3 months since the start of VenAza, 33.9% were on-treatment, 18.9% had died on-cycle, 35.8% went off-treatment due to progression or complications, and 7.6% underwent treatment intensification. Bone marrow CR rates in patients with a hematologic response were over 90% (reaching 100% in IC-eligible patients), with negative MRD in over 90% of CRs. Median overall survival (OS) was 19.4 months; patients 65 to 74 years-old had an estimated OS at 3 years of 65.9% with median not-reached (NR), and IC-eligible patients (all with non-favorable risk disease) had a 3-year OS of 57.3% with median NR. Our results in a population including younger and fitter patients compare favorably with the literature, including the median OS of 14.7 months obtained in the VIALE-A trial on older or unfit patients, and can help support the decision to treat IC-eligible patients less intensively when the likelihood of response to IC is low.