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BTK Inhibitor

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BTK Inhibitor, Bruton Tyrosine Kinase Inhibitor, Ibrutinib, Imbruvica, Acalabrutinib, Calquence

  • See Also
  1. Small Molecule Inhibitor-Mediated Chemotherapy
  2. Chemotherapy
  • Indications
  1. Mantle Cell Lymphoma (Acalabrutinib's only FDA approved indication)
  2. Chronic Lymphocytic Leukemia (17p deletion)
  3. Waldenstrom's Macroglobulinemia
  4. Marginal Zone Lymphoma
  5. Chronic Graft versys host disease
  • Contraindications
  1. Baseline hepatic Insufficiency (Ibrutinib)
  • Mechanism
  1. Bruton's Tyrosine Kinase (BTK)
    1. BTK is part of group of src-related BTK/Tec, cytoplasmic Tyrosine Kinases
    2. BTK is key to B Cell receptor signaling and B Cell maturation
    3. BTK Is overexpressed in some B Cell malignancies, which facilitates their proliferation
  2. BTK Inhibitor (Bruton Tyrosine Kinase Inhibitor)
    1. Orally active, small molecules that irreversibly bind and inhibit BTK
    2. Blocks B-Cell Activation and B-Cell mediated signaling
    3. Greatest effect is on malignant B Cells that overexpress BTK
    4. BTK Inhibitors also affect normal B Cells, and are used in chronic Graft Versus Host Disease
  • Medications
  1. Acalabrutinib (Calquence)
    1. Risks include secondary malignancy, myelosuppression (bleeding and infection risk), Atrial Fibrillation
    2. Avoid with strong CYP3A Inhibitors and Inducers (and adjust dose with moderate agents)
    3. Avoid Proton Pump Inhibitors (and spaced dosing of H2 Blockers) with Acalabrutinib
  2. Ibrutinib (Imbruvica)
    1. Risks include secondary malignancy, myelosuppression (bleeding and infection risk), Atrial Fibrillation
    2. Other risks include Tumor Lysis Syndrome
    3. Avoid with strong CYP3A Inhibitors and Inducers (and adjust dose with moderate agents)
    4. Avoid in hepatic insufficiency
  • Dosing
  1. See other references for disease specific dosing protocols
  • Adverse Effects
  1. Myelosuppression (all agents)
    1. Neutropenia (and infection risk)
    2. Thrombocytopenia (and Bleeding Diathesis)
  2. Secondary primary malignancies including Skin Cancer (all agents)
  3. Atrial Fibrillation or Atrial Flutter (all agents)
  4. Hypertension (Ibrutinib)
  5. Tumor Lysis Syndrome (Ibrutinib)
  6. Other adverse effects
    1. Diarrhea
    2. Edema
    3. Headache
    4. Dizziness
    5. Anxiety
    6. Rash
  • Safety
  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, pregnancy category X)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count
    2. Electrocardiogram (EKG) for Atrial Fibrillation or flutter
    3. Secondary malignancy surveillance including skin exams
  • Drug Interactions
  1. Strong CYP3A Inhibitors and Inducers
    1. Avoid strong inhibitor and inducers with Acalabrutinib or Ibrutinib
    2. Adjust dosing with moderate inhibitors and inducers
  2. Antacids
    1. Avoid Proton Pump Inhibitors (and spaced dosing of H2 Blockers) with Acalabrutinib
  • Resources
  1. Acalabrutinib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b1409184-3267-4d8c-8f17-4e01f69828b1
  2. Ibrutinib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dfd0279-ff17-4ea9-89be-9803c71bab44
  • References
  1. Alu (2022) J Hematol Oncol 15(1):138 +PMID: 36183125 [PubMed]
  2. Ringheim (2021) Front Immunol 12:662223 +PMID: 34803999 [PubMed]