LuciMido (Midostaurin)

About Midostaurin

Midostaurin is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.

Acute Myeloid Leukemia (AML)

Indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA-approved test

50 mg PO BID (~q12hr) on Days 8-21 of each cycle of induction with cytarabine and daunorubicin and on Days 8-21 of each cycle of consolidation with high-dose cytarabine

Take dose with food

Also see Administration

Systemic Mastocytosis (SM)

Indicated for adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL)

100 mg PO BID (~q12hr) with food

Continue treatment until disease progression or unacceptable toxicity

Dosage Modifications (ASM, SM-AHN, MCL)

ANC <1 x 10^9/L (without MCL) or ANC < 0.5 x 10^9/L with baseline ANC of 0.5-1.5 x 10^9/L

• Interrupt dosing until ANC ≥1 x 10^9/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
• Discontinue if low ANC persists for >21 days and is suspected to be related to midostaurin

Platelet count <50 x 10^9/L (without MCL) or <25 x 10^9/L with baseline of 25-75 x 10^9/L

• Interrupt dosing until platelet count ≥50 x 10^9/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
• Discontinue if low platelet count persists for >21 days and is suspected to be related to midostaurin

Hemoglobin <8 g/L (without MCL) or life-threatening anemia with baseline of 8-10 g/L

• Interrupt dosing until hemoglobin ≥8 g/L, then resume at 50 mg BID; if tolerated, increase to 100 mg BID
• Discontinue if low platelet count persists for >21 days and is suspected to be related to midostaurin

Grade 3 to 4 nausea and/or vomiting despite optimal antiemetic therapy

• Interrupt dosing for 3 days (6 doses), then resume at 50 mg BID; if tolerated, increase to 100 mg BID

Other grade 3 to 4 nonhematological toxicities

• Interrupt dosing until event has resolved to ≤grade 2, then resume at 50 mg BID; if tolerated, increase to 100 mg BID

Dosing Considerations

Administer prophylactic antiemetics before treatment to decrease risk of nausea and vomiting

AML

• Limitations of use: Not indicated as a single-agent induction therapy for AML
• Select patients for the treatment of AML based on the presence of FLT3 mutation positivity
• Information on FDA-approved tests for the detection of FLT3 mutation in AML is available at: https://www.fda.gov/CompanionDiagnostics

ASM, SM-AHN, and MCL

• Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment

Patient selection

• Select patients based on presence of FLT3 mutation in blood or bone marrow by LeukoStrat CDx FLT3 Mutation Assay