EORTC/GIMEMA trial shows combination of GO and chemotherapy provides no benefit for older patients with AML

Results of the randomized, phase III, EORTC/GIMEMA 06012 intergroup trial (AML-17) reported in the Journal of Clinical Oncology show that sequential combination of gemtuzumab ozogamicin (GO) and standard chemotherapy provides no benefit for older patients with acute myeloid leukemia (AML) and is too toxic for patients 70 years of age or more. GO is an antibody-drug conjugate comprised of an anti-CD33 monoclonal antibody linked to a cytotoxic agent.

Patients younger than 70 years with secondary acute myeloid leukemia might possibly benefit from such treatment. However, outcomes were significantly worse in the oldest age subgroup due to a higher risk of early mortality.

Prof. Sergio Amadori of the Tor Vergata University Hospital in Rome and Coordinator of this study says, "This large trial in older patients with AML is the third randomized study to assess the addition of GO to chemotherapy in elderly patients with AML. So, it is an important addition to the literature.

Unlike the two trials published so far (French ALFA-0701, and UK NCRI AML16), a higher dose of GO was used, and the GO in induction was given before standard induction chemotherapy. This turns out to be an important difference. While, as shown by the former trials, the addition of low doses of GO to chemotherapy resulted in a survival benefit for older patients with better-risk disease, our study clearly indicates that an intensification strategy combining two upfront higher doses of GO with sequential induction chemotherapy is highly myelosuppressive and not beneficial in older patients, particularly in the oldest age cohort where induction response and survival rates are significantly compromised due to excess early mortality. On the basis of the available studies, there is plausible evidence that lower doses of GO as an adjunct to standard chemotherapy may offer better outcomes for these patients with limited alternatives."

The EORTC GIMEMA trial included 472 patients with newly diagnosed acute myeloid leukemia who were between the ages of 61 and 75 years. Patients were randomly assigned to gemtuzumab ozogamicin (GO), 236 patients, or No GO, 236 patients, arms. The GO arm received a course of gemtuzumab ozogamicin followed by induction chemotherapy with mitoxantrone/cytarabine/etoposide. The No GO arm received only induction chemotherapy. Patients in remission received two consolidation courses with or without gemtuzumab ozogamicin.

Overall response rate was comparable in the two arms: 45% in the GO arm and 49% in the No GO arm. At a median follow-up of 5.2 years, the median overall survival, the primary endpoint, was 7.1 months in the GO arm and 10 months in the No GO arm (hazard ratio [HR], 1.20; 95% CI, 0.99 to 1.45; P = 0.07). Other survival endpoints were similar in both arms. Grade 3/4 hematologic and liver toxicity were greater in the GO arm.

The Intergroup EORTC/GIMEMA 06012 trial was coordinated by the EORTC Leukemia Group in collaboration with the GIMEMA Acute Leukemia Working Party and was conducted in 59 sites located in seven countries: Belgium, Croatia, France, Germany, Italy, Portugal, and The Netherlands. This trial was supported by an educational grant from Pfizer.