Outcomes with fractionated gemtuzumab ozogamicin in molecularly defined favorable-risk acute myeloid leukemia

Randomized trials of gemtuzumab ozogamicin (GO), a CD33 directed antibody-drug conjugate, in combination with conventional anthracycline- and cytarabine-based induction chemotherapy (IC) for acute myeloid leukemia (AML) have shown heterogeneous benefit [ 1 ]. High single-dose regimens such as that used in SWOG S0106 showed excess early death and no benefit, whereas fractionated dosing in ALFA-0701 improved event-free survival (EFS) without excess mortality [ 2 , 3 , 4 ]. A pivotal patient-level meta-analysis of five randomized trials established a clear survival benefit in patients with favorable-risk cytogenetics, with a 20% absolute overall survival (OS) improvement at 6 years, and a smaller intermediate-risk benefit, ~5% at 6 years, with no benefit in adverse-risk disease [ 5 , 6 ]. However, these analyses relied on cytogenetics alone and predate the molecular risk stratification of the 2022 European LeukemiaNet (ELN), which reclassifies a substantial proportion of patients relative to earlier schemes [ 7 , 8 , 9 ]. The randomized evidence is strongest in core binding factor (CBF) AML, where GO is now widely considered standard of care, whereas its use in the remainder of the ELN 2022 favorable-risk category is less well defined [ 9 ]. Similarly, while the NCCN and other guidelines recommend the use of GO in favorable-risk AML, they do not define which subgroups should be included [ 10 ].