On May 20, 2022, the FDA accelerated the approval of a new indication for azacitidine injection (Vidaza; Celgene) for the treatment of pediatric patients with newly diagnosed juvenile myelomonocytic leukemia (JMML).
The FDA granted this indication a breakthrough therapy designation. Azacitidine injection was previously approved for the treatment of patients with myelodysplastic syndromes.
This approval was based on the results of the AZA-JMML-001 study, an international, multicenter, open-label clinical trial that evaluated the pharmacokinetics, pharmacodynamics, safety, and activity of azacitidine before hematopoietic stem-cell transplant (HSCT) in 18 pediatric patients with JMML. The patients received intravenous (IV) azacitidine on days 1 to 7 of a 28-day cycle, for a minimum of 3 cycles and a maximum of 6 cycles. Patients were included in the study if they did not have disease progression or were not ready for HSCT between cycles 4 and 6.
The main efficacy outcome measures were clinical complete remission or partial remission according to the International Juvenile Myelomonocytic Leukemia Working Group response criteria at 3 months (cycle 3, day 28). The responses must have been sustained for at least 4 weeks in the 4-week period preceding or succeeding cycle 3, or for day 28.
Of the 18 patients, 9 (50%) patients had confirmed clinical responses. Of these 9 patients, 3 patients had a complete response and 6 patients had a partial response to IV azacitidine therapy. The median time to response was 1.2 months (range, 0.95-1.87 months).
The proportion of patients undergoing HSCT was 94%, and the median time to HSCT was 4.6 months (range, 2.8-19 months).
The most common (>30%) adverse reactions reported with IV azacitidine in pediatric patients with JMML were pyrexia, rash, upper respiratory tract infection, and anemia.
The recommended dose of IV azacitidine for patients aged 1 month to <1 year or those weighing <10 kg is 2.5 mg/kg; the recommended dose for patients aged ≥1 years and weighing ≥10 kg is 75 mg/m2.