From the Guidelines
Acalabrutinib is a Bruton's tyrosine kinase (BTK) inhibitor, belonging to the class of targeted cancer therapies known as kinase inhibitors. This classification is based on its mechanism of action, which involves selectively blocking the BTK enzyme, a crucial component in the B-cell receptor signaling pathway 1. By inhibiting this enzyme, acalabrutinib disrupts the growth and survival signals in malignant B cells, particularly in conditions like chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma.
Some key points to consider about acalabrutinib include:
- Its selective inhibition of the BTK enzyme, which is designed to reduce off-target effects compared to first-generation BTK inhibitors 1.
- The typical administration route is oral, usually as capsules taken twice daily.
- Potential side effects that require monitoring include infections, bleeding risks, and cardiac arrhythmias, though it generally has good tolerability compared to some other cancer therapies.
- Recent studies, such as the ELEVATE-TN trial, have shown superior efficacy of acalabrutinib-obinutuzumab versus chlorambucil-obinutuzumab in terms of progression-free survival (PFS) and overall survival (OS) 1.
Given the evidence from recent and high-quality studies like the one published in the Annals of Oncology 1, the use of acalabrutinib as a BTK inhibitor is supported for the treatment of specific hematological malignancies, highlighting its importance in the class of targeted cancer therapies.
From the FDA Drug Label
CALQUENCE (acalabrutinib) is a kinase inhibitor. Acalabrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK). The class of medication that acalabrutinib is in is a kinase inhibitor, specifically a Bruton tyrosine kinase (BTK) inhibitor 2 2.
- Main mechanism of action: inhibition of BTK enzymatic activity
- Key characteristic: forms a covalent bond with a cysteine residue in the BTK active site
From the Research
Classification of Acalabrutinib
- Acalabrutinib is classified as a Bruton tyrosine kinase (BTK) inhibitor 3, 4, 5, 6, 7
- It is a second-generation, highly selective, potent, covalent BTK inhibitor 3
- Acalabrutinib is an orally available, next-generation inhibitor of BTK 4, 5
- It is a covalent BTK inhibitor with a differentiated selectivity and in vivo potency profile 7
Mechanism of Action
- Acalabrutinib works by inhibiting the activity of Bruton tyrosine kinase (BTK), which prevents the activation of the B-cell receptor (BCR) signaling pathway 4, 6
- This inhibition prevents both B-cell activation and BTK-mediated activation of downstream survival pathways 4