EORTC/GIMEA

Results of a randomized phase III trial evaluating the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy provides no benefit in older patients with newly diagnosed acute myeloid leukemia (AML). The results of the EORTC/GIMEMA 06012 intergroup trial (AML-17) are published in the October 14, 2013 issue of the Journal of Clinical Oncology and also show that the combination is too toxic for patients 70 years of age or older. Gemtuzumab ozogamicin is an antibody-drug conjugate comprised of an anti-CD33 monoclonal antibody linked to a cytotoxic agent.

The study results show that 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.


An intensification strategy combining two upfront higher doses of gemtuzumab ozogamicin with sequential induction chemotherapy is highly myelosuppressive and not beneficial in older patients…


Professor Sergio Amadori, M.D. of the Tor Vergata University Hospital in Rome and Coordinator of this study noted: “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.”

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Other studies
Unlike the two trials published so far, the French ALFA-0701, and UK NCRI AML16 trial, a higher dose of GO was used. Furthermore, GO in induction was given before standard induction chemotherapy. According to the researchers, this turns out to be an important difference in the study design. 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, the AML17 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,” Amadori explained.

Study design
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.


Photo Credit: American Society of Hematology

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Last Editorial Review: April 5, 2019

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