On March 30, the U.S. Food and Drug Administration (FDA) approved a revised label for the combination of daunorubicin and cytarabine (Vyxeos) to include a new indication to treat newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes (AML-MRC) in pediatric patients aged 1 year and older. The approved agent is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor.
The approval of daunorubicin/cytarabine for this indication is supported by safety data from two single-arm trials: AAML1421, conducted by the Children's Oncology Group (COG), and CPX-MA-1201, conducted by Cincinnati Children's Hospital (CCH), as well as evidence of effectiveness from “an adequate and well-controlled study” (per FDA regulations) in adults.
More About AAML1421 and CPX-MA-1201
The safety and pharmacokinetics of daunorubicin/cytarabine in children and young adults were established in two clinical studies that enrolled patients with AML or relapsed/refractory hematologic malignancies. Thirty-eight pediatric patients aged 1 to 21 years with AML in first relapse were enrolled in the phase I/II AAML1421 study conducted by COG, and 27 patients aged 1 to 19 years with relapsed/refractory hematologic malignancies were enrolled in the phase I CPX-MA-1201 study conducted by CCH. Both studies found no differences in the safety profile based on age. The use of daunorubicin/cytarabine for this indication is also supported by evidence of effectiveness from the phase III CPX-351-301 study, which was conducted in adult patients.
The labeling for daunorubicin/cytarabine has a boxed warning, as it cannot be substituted with other daunorubicin and/or cytarabine-containing products. In the phase III study, the most common adverse reactions (incidence ≥ 25%) were bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting.
"The expansion of the … label to include children is a welcome and necessary advancement in support of some of our most vulnerable patients," said Edward Anders Kolb, MD, Director of the Center for Cancer and Blood Disorders at Nemours/Alfred I. DuPont Hospital for Children and Chair of the Myeloid Disease Committee at COG.