Gemtuzumab Ozogamicin Is an Effective First-Line AML Therapy

Systematic cytotoxic treatment with daunorubicin and cytarabine has been the standard induction regimen for patients with acute myeloid leukemia (AML) for decades, but targeted delivery of cytotoxic agents to leukemia cells may improve clinical outcome. In previous phase II and III clinical trials, the combination of gemtuzumab ozogamicin, a humanized anti-CD33 antibody conjugated to calicheamicin, with standard induction therapy elicited a complete response in some relapsed AML patients, but higher doses were associated with hematologic and hepatic toxicity and increased induction death. Castaigne and colleagues hypothesized that administration of fractionated low doses of gemtuzumab ozogamicin would minimize toxicity while allowing delivery of higher cumulative doses. Treatment-naïve AML patients, ages 50 to 70 years, without previous myeloproliferative or myelodysplastic syndrome were enrolled in a randomized, open-label phase III study comparing standard induction therapy with daunorubicin and cytarabine to standard induction therapy with three 3-mg/m² doses of gemtuzumab ozogamicin every 3 days (3-3-3 regimen). After induction therapy, the complete response rates were similar between the 2 groups (81% in the gemtuzumab ozogamicin group and 75% in the control group), but after 2 years, event-free survival, overall survival, and relapse-free survival were all significantly increased in the gemtuzumab ozogamicin group (40.8%, 53.2%, and 50.3%, respectively) compared with the control group (17.1%, 41.9%, and 22.7%, respectively). Of note, the benefit associated with gemtuzumab ozogamicin was most pronounced in patients with favorable or intermediate cytogenetics or FLT3 internal tandem duplication. The most frequent adverse events associated with gemtuzumab ozogamicin were delayed platelet recovery and persistent thrombocytopenia after chemotherapy, but the risk of treatment-related death was not increased. These findings suggest that the addition of fractionated low doses of gemtuzumab ozogamicin to standard induction therapy should be considered for older patients with de novo AML.

Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 2012 Apr 5 [Epub ahead of print].

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