Efficacy and challenges involving combination therapies in CLL

Majed A Alanazi; Faith A A Kwa; Musab M A Omar; Juliana Antonipillai; Denise E Jackson

doi:10.1016/j.drudis.2024.104243

Efficacy and challenges involving combination therapies in CLL

Drug Discov Today. 2024 Nov 17;29(12):104243. doi: 10.1016/j.drudis.2024.104243. Online ahead of print.

Authors

Majed A Alanazi¹, Faith A A Kwa², Musab M A Omar³, Juliana Antonipillai⁴, Denise E Jackson⁵

Affiliations

¹ Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia; Ministry of Education, Riyadh, Saudi Arabia.
² Faculty of Health, Arts & Design, Swinburne University, Melbourne, VIC, Australia.
³ Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia; Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia.
⁴ Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia.
⁵ Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC, Australia. Electronic address: denise.jackson@rmit.edu.au.

PMID: 39551090
DOI: 10.1016/j.drudis.2024.104243

Abstract

Chronic lymphocytic leukemia (CLL), a malignant tumour, is characterized by expansion of mature monoclonal B lymphocytes expressing CD23 and CD5 in secondary lymphocytic organs, blood, and bone marrow. Here, we provide an in-depth review of CLL, emphasizing its pathophysiology, cytogenic changes, and treatment strategies, particularly the efficacy and challenges of treatments, such as Bruton tyrosine kinase (BTK) inhibitors, B cell lymphoma 2 (BCL2) inhibitors, and phosphatidylinositol 3-kinase (PI3K) inhibitors, as well as the need to understand their role in managing disease progression, chemoresistance, and intolerance. In addition, we explore efficacy based on patient response and comparison between monotherapy and combination therapy. We also highlight the need for innovative strategies to overcome treatment resistance and enhance patient outcomes.

Keywords: BCL2 inhibitors; BTK inhibitors; Chronic lymphocytic leukemia (CLL); Cytogenetic changes; PI3K inhibitors; Treatment efficacy.

Publication types

Review