Updated safety of midostaurin plus chemotherapy in newly diagnosed FLT3 mutation-positive acute myeloid leukemia: the RADIUS-X expanded access program

Leuk Lymphoma. 2020 Dec;61(13):3146-3153. doi: 10.1080/10428194.2020.1805109. Epub 2020 Aug 19.


Approval of midostaurin, a multikinase inhibitor, in combination with chemotherapy for the treatment of adults with newly diagnosed FLT3 mutation-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.

Keywords: Acute myeloid leukemia; FLT3; idarubicin; maintenance; midostaurin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Protein Kinase Inhibitors / adverse effects
  • Radius*
  • Staurosporine / analogs & derivatives
  • fms-Like Tyrosine Kinase 3 / genetics


  • Protein Kinase Inhibitors
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Staurosporine
  • midostaurin

Associated data

  • ClinicalTrials.gov/NCT02624570