On May 20, 2022, azacitidine for injection was approved by the U.S. Food and Drug Administration for pediatric patients with newly diagnosed juvenile myelomonocytic leukemia.1
Supporting Efficacy Data
Approval was based on findings in the multicenter AZA-JMML-001 trial (ClinicalTrials.gov identifier NCT02447666), in which 18 patients (median age = 2.1 years) received intravenous azacitidine daily on days 1 to 7 of 28-day cycles for a minimum of three cycles and a maximum of six cycles, unless patients had disease progression or were ready for hematopoietic stem cell transplantation (HSCT) between cycles 4 and 6.
Clinical remission on international juvenile myelomonocytic leukemia response criteria at 3 months was observed in nine patients (50%, 95% confidence interval = 26%–74%), including complete remission in three. The median time to response was 1.2 months (range = 1–1.9 months). HSCT was performed in 94% of patients.
How It Is Used
The recommended dose for patients aged 1 month to up to 1 year r weighing up to 10 kg is 2.5 mg/kg. The recommended dose for patients aged aged 1 year or older and weighing at least 10 kg is 75 mg/m2. Treatment is given for 7 days in 28-day cycles for a minimum of three and a maximum of six cycles. A delay in dose not exceeding 14 days can be considered for nonhematologic toxicities. Dose reductions are not recommended for hematologic toxicity during the first three cycles. Treatment should be discontinued for patients with a neutrophil count less than 0.5 × 109/L at the end of cycle 3 or on day 1 of cycle 5 or 6.
Among the 18 patients receiving azacitidine in the AZA-JMML-001 trial, the most common adverse events of any grade were pyrexia (61%), rash (44%), upper respiratory tract infection (44%), anemia (39%), thrombocytopenia (28%), and vomiting (28%). The most common grade 3 or 4 adverse events were anemia (33%), thrombocytopenia (22%), neutropenia (11%), and abdominal pain (11%). Serious adverse events occurred in 67% of patients. Treatment was discontinued due to adverse events in one patient.
Azacitidine for injection has warnings/precautions for risk of substitution with other azacitidine products (eg, oral azacitidine); anemia, neutropenia, and thrombocytopenia; hepatotoxicity; renal toxicity; tumor-lysis syndrome; and embryofetal toxicity. This treatment is contraindicated in patients with advanced malignant hepatic tumors and in those with hypersensitivity to azacitidine or mannitol.
1. Vidaza (azacitidine for injection), for subcutaneous or intravenous use, prescribing information, Celgene Corporation, May 2022. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2022/050974s034lbl.pdf. Accessed June 6, 2022.