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