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Abstract
The use of irreversible inhibitors of Bruton tirosine kinase (BTK) represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). The first in-class, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström’s macroglobulinemia. More selective inhibitors are being studied. Acalabrutinib is a novel irreversible second-generation BTK inhibitor that was shown to be more selective and potent than ibrutinib. This may reduce toxicity related to off-target activity of ibrutinib on other kinases including EGFR, ITK and Tec family kinases, and may also overcome drug resistance related to incomplete BTK inhibition with the last, and may improve its toxicity profile. Studied for patients with CLL R/R, acalabrutinib is also being investigated for the frontline treatment of CLL as monotherapy and in combination. Recently it has received approval for the treatment for MCL in the relapsed/refractory setting.
References
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