Dr. Furman on Differences Between BTK Inhibitors in B-Cell Malignancies

Richard R. Furman, MD, professor of medicine; Morton Coleman, MD Distinguished Professor of Medicine; director of the CLL Research Center at Weill Cornell Medical College, Weill Cornell Medicine, and attending physician at New York-Presbyterian Hospital, discusses differences among the different available BTK inhibitors for use in patients with B-cell malignancies.

To date, ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) are the 3 BTK inhibitors that have received regulatory approval in the United States, Furman says. Ibrutinib is a first-generation BTK inhibitor while zanubrutinib and acalabrutinib are second-generation BTK inhibitors, Furman explains.

Since all 3 agents have the same bind covalently to the same residue and they operate using the same mechanism of action with regard to their efficacy, the main differences among them are in terms of their specificity and drug–drug interaction, Furman adds.

Notably, when comparing acalabrutinib and zanubrutinib with ibrutinib, fewer off-target effects are observed. The safety profiles of these drugs also differ, Furman adds. Additionally, because of the differences in how these BTK inhibitors are metabolized, there is a significant contrast in the way they interact with other drugs, Furman concludes.