II. 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

III. Contraindications

  1. Baseline hepatic Insufficiency (Ibrutinib)

IV. 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

V. 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

VI. Dosing

  1. See other references for disease specific dosing protocols

VII. 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

VIII. 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

IX. 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

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Ontology: Ibrutinib (C3501358)

Definition (NCI) An orally bioavailable, small-molecule inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon oral administration, ibrutinib binds to and irreversibly inhibits BTK activity, thereby preventing both B-cell activation and B-cell-mediated signaling. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is required for B cell receptor signaling, plays a key role in B-cell maturation, and is overexpressed in a number of B-cell malignancies. The expression of BTK in tumor cells is also associated with increased proliferation and survival.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C551803
English ibrutinib, 2-Propen-1-one, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1h-pyrazolo(3,4-d)pyrimidin-1-yl)-1-piperidinyl)-, Ibrutinib, IBRUTINIB