Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial

The randomized, phase 3 ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin added to standard front-line chemotherapy significantly improves event-free survival in adults with de novo acute myeloid leukemia. Here we report an independent review of event-free survival, final overall survival, and additional safety results from ALFA-0701. Patients (N=271) aged 50-70 years with de novo acute myeloid leukemia were randomized to receive conventional front-line induction chemotherapy (3+7 daunorubicin+cytarabine) with/without gemtuzumab ozogamicin 3 mg/m2 on days 1, 4, and 7 during induction. Patients in remission following induction therapy received 2 courses of consolidation therapy (daunorubicin+cytarabine) with/without gemtuzumab ozogamicin (3 mg/2;/day on day 1) according to their initial randomization. The primary endpoint was investigator-assessed event-free survival. Secondary endpoints included overall survival and safety. A blinded independent review confirmed the investigator-assessed event-free survival results (August 1, 2011; hazard ratio, 0.66 [95% CI, 0.49-0.89]; 2-sided p=0.006), corresponding to a 34% reduction in risk of events in the gemtuzumab ozogamicin versus control arm. Final overall survival (April 30, 2013) favored gemtuzumab ozogamicin but was not significant. No differences were observed between arms in early death rate. The main toxicity associated with gemtuzumab ozogamicin was prolonged thrombocytopenia. Veno-occlusive disease (including after transplant) was observed in 6 patients in the gemtuzumab ozogamicin arm and 2 in the control arm. In conclusion, gemtuzumab ozogamicin added to standard intensive chemotherapy has a favorable benefit/risk ratio. These results expand front-line treatment options for adult patients with previously untreated acute myeloid leukemia. (ClinicalTrials.gov identifier: NCT00927498)