Sequentially combining gemtuzumab ozogamicin (GO) and standard chemotherapy provides no benefit for older patients with acute myeloid leukemia (AML) and is too toxic for patients age 70 years or older. These results were determined by a randomized, phase III, EORTC/GIMEMA 06012 intergroup trial (AML-17). 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. The results were reported in the Journal of Clinical Oncology (2013; doi:10.1200/JCO.2013.49.0771).

“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,” said study coordinator Sergio Amadori, MD, of the Tor Vergata University Hospital in Rome.

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Amadori explained that the dose of GO and sequence of giving GO before standard induction chemotherapy was an important difference. Adding low doses of GO to chemotherapy in earlier trials resulted in a survival benefit for older patients with better-risk disease. However, Amadori stated that this study clearly indicated 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.

For these patients with limited alternatives, Amadori said, “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.”

The EORTC GIMEMA trial included 472 patients with newly diagnosed acute myeloid leukemia who were age 61 to 75 years. Patients were randomly assigned to 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, which was the primary end point, was 7.1 months in the GO arm and 10 months in the No GO arm. Other survival end points were similar in both arms. Grade 3/4 hematologic and liver toxicity were greater in the GO arm.