Despite having revolutionized the management of R/R MCL and CLL, covalent inhibitors of BTK demonstrate increased protein binding, have short half-lives, and exhibit decreased oral bioavailability, with only brief exposure to inactivate BTK. One-third of patients will develop primary BTK inhibitor resistance, and nearly all develop secondary resistance—despite response rates of single-agent BTK inhibitors being relatively high. Mechanisms of resistance to covalent BTK inhibitors are not fully elucidated and differ by malignancy type. Resistance, intolerance, toxicity, and disease progression are all factors that contribute to treatment discontinuation in patients taking covalent BTK inhibitors.
When covalent BTK inhibitors are no longer an option, noncovalent BTK inhibitors that are highly selective for BTK can reestablish response and propel the care of patients with R/R MCL and CLL forward. Efficacy of BTK inhibition delivered via noncovalent BTK inhibition could permit patients with B-cell malignancies to further extend the clinical benefit delivered via BTK inhibition by permitting the sequential use of inhibitors that bind by means of both covalent and noncovalent mechanisms.
Which of your patients are best suited for treatment with noncovalent BTK inhibitors?
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MATTHEW MCCARTY2yrI use a non covalent btk in the third line setting after covalent btk and bcl2
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Sanjaykumar Hapani, MERCY HOSPITAL OKLAHOMA CITY, INC2yrOVerall car-t ability to be deilivered in outpatient non-academic centers will allow us to help more patients
