Drug1st line

Midostaurin (Rydapt)

Multikinase inhibitor (KIT, FLT3, PDGFR, PKC)

Response rate
60% ORR in AdvSM; 45% major response
Onset
Weeks–months
Route
Oral 100mg twice daily
Line
1st
IgM effect
N/A
Evidence level
green
Trial phase
Phase 4

Evidence summary

First FDA-approved KIT inhibitor for advanced SM (April 2017). In the landmark phase II trial (NEJM 2016), midostaurin achieved 60% ORR with 45% major responses in 89 evaluable AdvSM patients. Median OS 28.7 months. Active against both wild-type and D816V-mutated KIT. Less selective than avapritinib, with higher rates of GI toxicity.

Approved indications

Conditions for which Midostaurin (Rydapt) has regulatory approval (not specific to rare diseases covered here):

Advanced systemic mastocytosisFLT3-mutated AML

Drug identifiers

DrugBankDB06595
ATC CodeL01EX10

Sources (3)

DetailsGotlib J et al. (2016) Efficacy and Safety of Midostaurin in Advanced Systemic MastocytosisDOI
DetailsGotlib J et al. (2018) FDA Approval Summary: Midostaurin for the Treatment of Advanced Systemic MastocytosisDOI
DetailsDeAngelo DJ et al. (2018) Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trialDOI