Roboz, Gail J.; Strickland, Stephen A.; Litzow, Mark R.; Dalovisio, Andrew; Perl, Alexander E.; Bonifacio, Gaetano; Haines, Kelly; Barbera, Alysha; Purkayastha, Das; Sweets, Kendra
Approval of midostaurin, a multikinase inhibitor, in combination with chemotherapy for the treatment of adults with newly diagnosedFLT3mutation-positive acute myeloid leukemia, was based on the phase 3 RATIFY trial results. RADIUS-X (NCT02624570) was an expanded access program providing access to midostaurin during regulatory review and extending the understanding of the safety and tolerability of midostaurin. Patients aged >= 18 years received midostaurin with 1-2 cycles of induction therapy (cytarabine plus daunorubicin or idarubicin) and <= 4 cycles of high-dose cytarabine consolidation chemotherapy or as single-agent maintenance therapy. The study enrolled 103 patients. No new safety events were observed; toxicities were not influenced by age, anthracycline choice, or coadministration of CYP3A4 inhibitors. The most common adverse events (AEs) were febrile neutropenia, nausea, and diarrhea. During maintenance, 46% of patients reported AEs. Midostaurin demonstrated a manageable safety profile and was associated with high transplant and low on-treatment relapse rates.