Leukaemia: Crowd control.

Nature reviews. Cancer 2017

Ulrike Harjes

Abstract

Standard frontline treatment of chronic lymphocytic leukemia (CLL) is with fixed-duration venetoclax-based doublets or indefinite covalent Bruton tyrosine kinase inhibitor (BTKI). Although these approaches achieve excellent results, venetoclax doublets have diminished efficacy in high-risk biological subgroups, and indefinite covalent Bruton tyrosine kinase inhibitor (cBTKI) is associated with cumulative cardiovascular and infectious toxicity. Triplet regimens for treatment of CLL involve simultaneous use of cBTKI, venetoclax, and anti-CD20 monoclonal antibody. Three major frontline Phase 3 trials (CLL-13/GAIA, AMPLIFY, and A041702) have demonstrated higher rates of undetectable minimal residual disease (uMRD) and longer remissions with triplets than doublets, particularly in patients with IGHV-unmutated (IGHV-U) disease. However, this comes at the cost of increased infectious toxicity, particularly with COVID-19, and thus has translated into a variable impact on progression-free survival (PFS) and, to-date, no overall survival (OS) benefit. Although there are promising Phase 2 data for triplets in patients with

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