Beyond ibrutinib: novel BTK inhibitors for the treatment of chronic lymphocytic leukemia. Issue 6 (22nd November 2022)

• Record Type: Journal Article
• Authors: Perutelli, Francesca; Montalbano, Maria Chiara; Boccellato, Elia; Coscia, Marta; Vitale, Candida
• Is Part Of: Current opinion in oncology. Volume 34:Issue 6(2022)
• Page Start: 757
• Page End: 767
• Publication Date: 2022-11-22
• Subjects: acalabrutinib -- BTK inhibitors -- chronic lymphocytic leukemia -- pirtobrutinib -- zanubrutinib; Oncology -- Periodicals; 616.994
• DOI: 10.1097/CCO.0000000000000897
• Languages: English
• ISSNs: 1040-8746

Abstract

Abstract : Purpose of the review: Ibrutinib was the first Bruton tyrosine kinase inhibitor (BTKi) approved for clinical use, contributing to a dramatic change in the treatment landscape of chronic lymphocytic leukemia (CLL). This review provides an overview of next-generation BTKi that have been recently approved or are being investigated for the treatment of CLL, specifically highlighting differences and similarities compared to ibrutinib. Recent findings: Acalabrutinib presented comparable response rates to ibrutinib with lower rates of adverse events and is currently approved for the treatment of CLL. Zanubrutinib displayed excellent response rates with a lower incidence of BTKi-related adverse events, but major rates of neutropenia, and its approval is awaited. With the aim of overcoming drug resistance, noncovalent BTKi have been developed. Of all the explored agents to date, pirtobrutinib has shown promising results with manageable toxicities. Summary: For the treatment of CLL, several effective therapeutic strategies to target BTK are or will soon be available: these drugs present different safety profiles, thus making it possible to tailor the treatment choice according to patient's characteristics. Importantly, noncovalent BTKi will provide a therapeutic chance also for those relapsed/refractory CLL patients who are BTKi-resistant and are considered an unmet clinical need.