Ready, set, GO? Treating older adults with AML

In this issue of Blood, Knapper et al 1 report the results of a large, randomized trial of daunorubicin and cytarabine with 2 doses of gemtuzumab ozogamicin (GO; DAGO2) vs CPX-351 in older adults with acute myeloid leukemia (AML) without adverse cytogenetics.The original primary end point of the study was overall survival (OS).However, because of accrual being affected by the COVID-19 pandemic, the primary end point was changed to event-free survival (EFS), with an event being defined as resistance to treatment (refractory disease or partial response after course 2), relapse, or death.GO is an antibody-drug conjugate comprising a monoclonal antibody targeting CD33 and calicheamicin.Although it was initially approved by the US Food and Drug Administration (FDA) in 2000, it was recalled in 2010 after observations of increased early mortality when added to standard induction chemotherapy. 2That study, as well as other early studies, used GO at doses of 6 to 9 mg/m 2 .The UK National Cancer Research Institute (NCRI) pioneered lower doses of 3 mg/m 2 , capped at 5 mg, with no added hepatotoxicity, and demonstrated that the addition of GO benefited patients with AML with favorable-risk cytogenetics.These findings were subsequently confirmed by a large meta-analysis, which demonstrated the benefit of GO in both favorable-and intermediate-risk AML. 3 This supported reapproval by the FDA in 2017.More recently, the NCRI showed that giving 2 doses of GO with intensive chemotherapy was associated with improved OS over a single dose of GO in patients with nonadverse cytogenetics. 4