September 22, 2023

US FDA Approves Midostaurin for Treatment of Acute Myeloid Leukemia

The US FDA approved the use of Rydapt (midostaurin) in combination with chemotherapy for treating recently diagnosed adults with acute myeloid leukemia (AML), having a particular genetic mutation – FLT3 by Novartis. The drug is used in combination with standard induction using cytarabine and daunorubicin, and consolidation using cytarabine. The FDA has also approved the companion diagnostic test that enables detection of the FLT3 mutation – LeukoStrat CDx FLT3 Mutation Assay by Invivoscribe Technologies Inc.1,2

Acute myeloid leukemia encompasses a group of relatively well-defined hematopoietic neoplasms. A recent systematic literature review of AML revealed its prevalence ranged between 0.6–11.0 per 100,000 for all ages, ethnicities, and both genders.3

How it works:

Midostaurin, a multikinase inhibitor, is the first targeted therapy demonstrating improvement in overall survival (OS) in AML patients with the FLT3 mutation.4 Midostaurin inhibits FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, SRC, cyclin-dependent kinase 1, vascular endothelial growth factor receptor, and C-kit.5 It demonstrates single agent activity in both internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutant FLT3 AML.6

High-risk patients with AML and FLT3 mutations who were administered midostaurin plus standard chemotherapy showed improved survival compared to those on placebo plus chemotherapy.4 In the C10603 trial, 717 pre-therapy genetically defined subgroup of AML patients were randomized to either midostaurin (n=360) or placebo (n=357). The addition of midostaurin to standard chemotherapy and maintenance therapy (1 year) lead to a significant improvement in event free survival and overall survival  in patients whose blasts had a TKD or ITD (low or high FLT3 mutation burden).6

There were no statistically significant differences between the midostaurin and placebo groups in the overall rate of grade 3 or higher adverse events (hematologic or non-hematologic). Also, no differences were observed in treatment-related grade 5 adverse events.6

Side effects of Midostaurin:

In AML patients, the frequently observed side effects of midostaurin are febrile neutropenia, nausea and vomiting, headache, mucosal inflammation, petechial hemorrhages, epistaxis, musculoskeletal pain, device-related infection, hyperglycemia, and upper respiratory tract infection. Midostaurin is contraindicated in patients with hypersensitivity to midostaurin and pregnant or breastfeeding women. Development of signs and symptoms of pulmonary toxicity should lead to its discontinuation.1

Midostaurin has also been approved for the treatment of some rare adult hematological disorders, namely, aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm or mast cell leukemia. 1 In an open-label study, oral midostaurin was administered twice daily to 116 patients. The overall response rate observed was 60%, with 45% of the patients having a major response (complete resolution of at least one type of mastocytosis-related organ damage). The median overall survival and the median progression-free survival were 28.7 months and 14.1 months, respectively. The most common side effects of midostaurin in these patients were low-grade nausea, vomiting, and diarrhea. Other adverse events included peripheral edema, musculoskeletal pain, fatigue, abdominal pain, constipation, headache, pyrexia, and dyspnea.7

The recommended doses of midostaurin are detailed in the table below.2

Indication Dose
AML On days 8 to 21 of each cycle of induction and consolidation chemotherapy: 50 mg twice a day with food

Followed by 50 mg with food (as a single agent) for up to 12 months

Aggressive SM, SM with hematological neoplasm, or mast cell leukemia 100 mg twice a day with food


Credit: Dr. Rachita on behalf of Borderless Access

Copyright © 2017 BorderlessAccess




  1. FDA News Release – FDA approves new combination treatment for acute myeloid leukemia. U.S. Food & Drug Administration Website.
  2. Midostaurin. U.S. Food & Drug Administration Website
  3. Lubeck DP, Danese M, Jennifer D, Miller K, Richhariya A, Garfin PM. Systematic literature review of the global incidence and prevalence of myelodysplastic syndrome and acute myeloid leukemia
  4. Starr P. Midostaurin the first targeted therapy to improve survival in AML: Potentially practice-changing. Am Health Drug Benefits.
  5. Gallogly MM, Lazarus HM. Midostaurin: An emerging treatment for acute myeloid leukemia patients.
  6. Paper presented at: American Society of Hematology (ASH) 57th Annual Meeting; December 3–6, 2015; Orlando, FL, USA
  7. Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis.
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