Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Zanubrutinib: Coming of Age for BTK Inhibitors in the Treatment of Chronic Lymphocytic Leukemia?

Version 1 : Received: 24 April 2023 / Approved: 24 April 2023 / Online: 24 April 2023 (09:43:47 CEST)
Version 2 : Received: 19 May 2023 / Approved: 22 May 2023 / Online: 22 May 2023 (16:15:16 CEST)

A peer-reviewed article of this Preprint also exists.

Molica, S.; Tam, C.; Allsup, D.; Polliack, A. Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option. Cancers 2023, 15, 3737. Molica, S.; Tam, C.; Allsup, D.; Polliack, A. Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option. Cancers 2023, 15, 3737.

Abstract

Ibrutinib, a first-in-class Bruton’s Tyrosine Kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated, and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by significant off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine–rituximab (BR) in treatment-naive CLL patients with an acceptable safety profile. More recently, data from the phase III ALPINE trial which directly compared zanu with ibrutinib has demonstrated that zanu’s advantages are both an improved safety profile and enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and newly released German CLL algorithm, suggest that zanu may replace first-generation BTKi as one of the preferred therapeutic options for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile.

Keywords

CLL, Zanubrutinib, BTK inhibitors, efficacy, safety, chronic lymphocytic leukemia

Subject

Medicine and Pharmacology, Hematology

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