Mylotarg® (gemtuzumab ozogamicin)—a drug that was withdrawn from the market in 2010 because of uncertain benefit and safety concerns—reduces the risk of relapse in children and young adults with acute myeloid leukemia (AML). These results were presented at the 2013 Annual Meeting of the American Society of Hematology.
Mylotarg was originally approved in 2000 under the U.S. Food and Drug Administration’s accelerated approval program. This program allows the FDA to approve a drug to treat serious diseases with an unmet need based on a surrogate endpoint (a laboratory measurement or a physical sign used as a substitute for a clinically meaningful endpoint such as survival). Drugs with accelerated approval must be further tested after approval to confirm a benefit. If the expected benefit is not confirmed, the FDA can withdraw the drug from the market.
Mylotarg was approved to treat patients ages 60 years and older with recurrent AML who were not candidates for other chemotherapy. The surrogate endpoint that prompted accelerated approval was response rate (the percentage of patients whose leukemia decreased or disappeared).
After approval, a confirmatory clinical trial was conducted to determine whether Mylotarg improved survival with AML. The study—which compared treatment with chemotherapy and Mylotarg to treatment with chemotherapy alone—was stopped early when Mylotarg failed to provide a clinical benefit, and after a greater number of deaths occurred among patients treated with Mylotarg.
The current Phase III clinical trial was conducted by the Children’s Oncology Group. The study enrolled 1,070 children and young adults with AML. Study participants were assigned to standard therapy alone or in combination with Mylotarg. Stem cell transplantation was used for high-risk patients and for intermediate-risk patients with a matched family donor.
- The addition of Mylotarg reduced the risk of relapse. After three years, relapses had occurred in 33% of patients who received Mylotarg and 41% of patients who did not receive Mylotarg. Mylotarg did not have a significant effect on overall survival.
- Serious side effects (including death) were more common in the Mylotarg group. Treatment-related death occurred in 6.6% of the patients who received Mylotarg and 4% of patients who did not receive Mylotarg.
These results suggest that Mylotarg may provide a benefit in the treatment of AML in children and young adults.
Reference: Gamis AS, Aplenc R, Alonzo TA et al. Gemtuzumab Ozogamicin (GO) In Children With De NovoAcute Myeloid Leukemia (AML) Improves Event-Free Survival (EFS) By Reducing Relapse Risk – Results From The Randomized Phase III Children’s Oncology Group (COG) Trial, AAML0531. Presented at the 55thASH Annual Meeting and Exposition. New Orleans, LA. December 7-10, 2013. Abstract 355.