Identifying Differences Between BTK Inhibitors for B-Cell Malignancies

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Richard R. Furman, MD, discusses the distinguishing features between the 3 different Bruton’s tyrosine kinase inhibitors as treatment of patients with B-cell malignancies.

Richard R. Furman, MD, professor of medicine, Morton Coleman, MD Distinguished Professor of Medicine, director, CLL Research Center, Weill Cornell Medicine, and attending physician, NewYork-Presbyterian Hospital, discusses the distinguishing features between the 3 different Bruton’s tyrosine kinase (BTK) inhibitors as treatment of patients with B-cell malignancies.

Ibrutinib (Imbruvica) is a first-generation BTK inhibitor, says Furman, and zanubrutinib (Brukinsa) and acalabrutinib (Calquence) are second-generation inhibitors. Because all 3 of these agents covalently bind to the same residue and work through the same mechanism in terms of their efficacy, the only difference is the specificity and the drug to drug interaction, according to Furman.

Because of the difference in specificity, there are fewer off-target effects with the second-generation BTK inhibitors compared with ibrutinib. This also leads to different adverse event profiles, says Furman. Because of the differences in how the drugs are metabolized, there are also differences in their interactions with other drugs.

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