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FLT3 Inhibitor

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FLT3 Inhibitor, FLT3 Kinase Inhibitor, FMS-like Tyrosine Kinase 3, Fetal Liver Tyrosine Kinase 3, CD135, Crenolanib, Gilteritinib, Xospata, Midostaurin, Rydapt

  • See Also
  1. Small Molecule Inhibitor-Mediated Chemotherapy
  2. Chemotherapy
  • Indications
  1. Acute Myelogenous Leukemia (FLT3+ new or advanced/refractory)
    1. Gilteritinib (Xospata)
    2. Midostaurin (Rydapt)
  2. Severe Systemic Mastocytosis
    1. Midostaurin (Rydapt)
  • Mechanism
  1. FLT3 Tyrosine Kinase (FMS-like Tyrosine Kinase 3)
    1. Tyrosine Kinase Receptor
    2. Regulates the survival and proliferation of hematopoietic stem cells and progenitor cells
  2. FLT3 Mutations
    1. FLT3 mutations are found in one third of Acute Myelogenous Leukemia cases
  3. FLT3 Inhibitors
    1. FLT3 Inhibitors suppress only peripheral AML progenitor cells (blasts), NOT marrow cells
  • Medications
  1. Gilteritinib (Xospata)
    1. Risk of differentiation syndrome, PRES, Prolonged QTc, Pancreatitis
  2. Midostaurin (Rydapt)
    1. Risk of Interstitial Lung Disease, QTc Prolongation
  3. Crenolanib
    1. Orally benzimidazole small molecule agent
    2. Active against FLT3 (FMS-like Tyrosine Kinase 3)
    3. Active against Platelet-derived growth factor receptor (PDGFR, alpha and beta)
  • Dosing
  1. See other references for disease specific dosing protocols
  • Safety
  1. Avoid in Lactation
    1. Avoid Breast Feeding for 2 months after Gilteritinib
  2. Avoid in pregnancy (all trimesters, pregnancy category X)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count
    2. Electrocardiogram (for QTc Prolongation)
  • Adverse Effects
  1. Differentiation Syndrome (Gilteritinib)
    1. Life threatening condition, rapid myeloid cell proliferation and differentiation
    2. May present with acute respiratory distress, Acute Kidney Injury, fever, edema
    3. Onset in the first 10 weeks of therapy requiring prompt initiation of Corticosteroids
  2. Posterior Reversible Encephalopathy Syndrome or PRES (Gilteritinib)
  3. Prolonged QTc (Gilteritinib, Midostaurin)
  4. Acute Pancreatitis (Gilteritinib)
  5. Interstitial Lung Disease (Midostaurin)
  6. Other reported adverse effects
    1. Hepatotoxicity
    2. Rash
    3. Vomiting
  • Drug Interactions
  1. Strong CYP3A4 Inhibitor and Inducers
    1. Avoid with Gilteritinib and Midostaurin
  2. Medication Causes of QTc Prolongation
    1. Avoid with Gilteritinib and Midostaurin
  • Resources
  1. Gilteritinib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5ff59aa-9c0d-49a8-9053-1f179b482383
  2. Midostaurin (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=11fa3fc9-6776-49a6-b1c1-653f627c3e58
  • References
  1. Zhao (2022) Blood Rev 52:100905 +PMID: 34774343 [PubMed]