open access

Vol 53, No 2 (2022)
Review article
Submitted: 2022-01-11
Accepted: 2022-01-31
Published online: 2022-04-06
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Chronic lymphocytic leukemia following venetoclax treatment failure

Oktawia Sośnia1, Bartosz Puła1
DOI: 10.5603/AHP.a2022.0013
·
Acta Haematol Pol 2022;53(2):94-103.
Affiliations
  1. Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

open access

Vol 53, No 2 (2022)
REVIEW ARTICLE
Submitted: 2022-01-11
Accepted: 2022-01-31
Published online: 2022-04-06

Abstract

Venetoclax (ABT-199) is a highly selective and potent inhibitor of BCL-2, capable of inducing deep remission in chronic lymphocytic leukemia (CLL). The introduction of this compound to the treatment armamentarium of CLL represented a real breakthrough, as the drug is effective in high-risk CLL patients and in the setting of Bruton’s tyrosine kinase inhibitors (BTKi) failure. Nevertheless, treatment failure or progression following venetoclax treatment occurs over time. Potential mechanisms of refractoriness, including BCL-2 mutations or activation of alternative anti-apoptotic pathways, have been identified. So far, questions regarding patient management after venetoclax and venetoclax-based regimen failure have yet to be answered, and only a few studies have addressed this problem. With increasing use of venetoclax-based treatment, the optimal sequencing and the most suitable next line treatment should be addressed in upcoming guidelines. In this review, we summarize the possible mechanism of resistance to venetoclax, and explore possible therapeutic options in cases of venetoclax failure.

Abstract

Venetoclax (ABT-199) is a highly selective and potent inhibitor of BCL-2, capable of inducing deep remission in chronic lymphocytic leukemia (CLL). The introduction of this compound to the treatment armamentarium of CLL represented a real breakthrough, as the drug is effective in high-risk CLL patients and in the setting of Bruton’s tyrosine kinase inhibitors (BTKi) failure. Nevertheless, treatment failure or progression following venetoclax treatment occurs over time. Potential mechanisms of refractoriness, including BCL-2 mutations or activation of alternative anti-apoptotic pathways, have been identified. So far, questions regarding patient management after venetoclax and venetoclax-based regimen failure have yet to be answered, and only a few studies have addressed this problem. With increasing use of venetoclax-based treatment, the optimal sequencing and the most suitable next line treatment should be addressed in upcoming guidelines. In this review, we summarize the possible mechanism of resistance to venetoclax, and explore possible therapeutic options in cases of venetoclax failure.

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Keywords

chronic lymphocytic leukemia, immunochemotherapy, ibrutinib, venetoclax, resistance

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About this article
Title

Chronic lymphocytic leukemia following venetoclax treatment failure

Journal

Acta Haematologica Polonica

Issue

Vol 53, No 2 (2022)

Article type

Review article

Pages

94-103

Published online

2022-04-06

Page views

187

Article views/downloads

49

DOI

10.5603/AHP.a2022.0013

Bibliographic record

Acta Haematol Pol 2022;53(2):94-103.

Keywords

chronic lymphocytic leukemia
immunochemotherapy
ibrutinib
venetoclax
resistance

Authors

Oktawia Sośnia
Bartosz Puła

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