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Frontline Therapy of CLL—Changing Treatment Paradigms

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Abstract

Purpose of Review

The therapeutic landscape for chronic lymphocytic leukemia (CLL) has undergone a complete makeover following the introduction of highly effective targeted therapies, beginning with ibrutinib which first attained regulatory approval for CLL in 2014.

Recent Findings

In recent years, we have seen further refinement of therapeutic options with the development of newer-generation Bruton’s tyrosine kinase inhibitors (BTKi) including acalabrutinib and zanubrutinib that improve upon the safety of ibrutinib. Additionally, venetoclax-based approaches, combined with anti-CD20 antibodies, have allowed for time-limited targeted therapeutic strategies which are particularly attractive for certain subsets of patients though have demonstrated efficacy across all subgroups. Lastly, there is an ongoing movement toward the development of time-limited strategies inclusive of both a BTKi and venetoclax that may further widen potential options.

Summary

CLL patients requiring frontline therapy have a unique burden of choice between highly effective therapies that differ substantially with respect to side effect profiles and schedules. This review will focus on the frontline management of CLL in the setting of these rapidly changing options.

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    Catherine C. Coombs

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C.C.C. wrote the manuscript text and prepared the table/figure. CCC has received honoraria/served as a consultant for AbbVie, Allogene, AstraZeneca, Beigene, Genentech, Janssen, Lilly, MEI Pharma, Mingsight, Octapharma, TG Therapeutics, has served on speaker’s bureau for AbbVie, AstraZeneca, Beigene, Genentech, and has received research funding (paid to institution) from AbbVie, CarnaBio, Lilly.

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Coombs, C.C. Frontline Therapy of CLL—Changing Treatment Paradigms. Curr Hematol Malig Rep 19, 65–74 (2024). https://doi.org/10.1007/s11899-024-00726-x

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