Children with newly diagnosed acute myeloid leukemia (AML) in Europe will not gain a new targeted option for now. The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) has finalized its assessment of an application to extend the use of Mylotarg (gemtuzumab ozogamicin, Pfizer) to children aged 1 year to less than 18 years with newly diagnosed AML, in combination with cytarabine and mitoxantrone. The committee did not recommend the new use.

However, the agency agreed that relevant data from the study submitted with the application will be added to the product information. This will give healthcare professionals up-to-date information on the effects of Mylotarg in these patients.

AML is a rare and aggressive blood cancer. Mylotarg is currently authorized in the EU for patients aged 15 years or older with previously untreated, de novo CD33-positive AML, excluding acute promyelocytic leukemia (APL), in combination with cytarabine and daunorubicin. The medicine has been authorized since April 2018 and received orphan designation in October 2000.

Mechanism of Action 

Mylotarg is an antibody-drug conjugate given by intravenous infusion, which can take 2 hours to administer. Its monoclonal antibody component, gemtuzumab, binds to CD33 on leukemia cells. Once internalized, the cytotoxic agent calicheamicin is released and breaks apart the cells' DNA, leading to cell death. The EMA said Mylotarg was expected to work the same way in children as in its existing indication.

Evidence Reviewed 

The company's main evidence came from a study of 515 children aged 1 year to less than 18 years, most with newly diagnosed, previously untreated CD33-positive AML (excluding APL). All participants received gemtuzumab ozogamicin plus cytarabine and mitoxantrone during the first induction course, either as one dose or three doses. The study was designed to test whether three doses were more effective than one. The main measure was event-free survival (EFS), defined as the time until loss of complete remission, relapse, a second unrelated cancer, or death. Overall survival was also assessed.

Supporting data came from a study of 1063 children and young adults with newly diagnosed de novo AML. That study compared standard chemotherapy alone with the same chemotherapy plus two doses of gemtuzumab ozogamicin.

Reason for Not Recommending the Extension 

The EMA concluded that the main study did not establish effectiveness. It did not show that gemtuzumab ozogamicin improved EFS. Also, because every child received the drug, the study could not show whether treatment with it was better than without it. The lack of a comparator also made it difficult to judge the drug's contribution to the overall risk of side effects.

The supportive study did show improved EFS with gemtuzumab ozogamicin, but this was not accompanied by better overall survival. More deaths also occurred among patients in the gemtuzumab ozogamicin group who had achieved complete remission. The agency noted additional uncertainties in how the two main efficacy measures were evaluated, and a higher proportion of patients in the gemtuzumab ozogamicin group had incomplete data relevant to EFS assessment.

The relevance of the supportive findings to the main study was also uncertain, because the studies used different treatment schedules and chemotherapy regimens. In the supportive study, gemtuzumab ozogamicin was given during both induction and intensification, whereas the main study used it during induction only.

On safety, the main study collected only selected prespecified side effects and only for 30 days after treatment. At that point many patients still had side effects, particularly neutropenia, which limited the safety assessment.

Next Steps 

The prescribing information for Mylotarg will be updated to include the relevant pediatric data. The EMA said there are no consequences for the authorized use in patients aged 15 years or older. The company also informed the agency that patients in clinical trials using Mylotarg are not affected. Patients in clinical trials or compassionate use programs who need more information should speak with their doctors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.