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Review
. 2024 Sep:201:104408.
doi: 10.1016/j.critrevonc.2024.104408. Epub 2024 Jun 14.

Severe infections in patients with chronic lymphocytic leukemia included in trials investigating BTK and BCL2 inhibitors

Francesca R Mauro  1 , Anna Maria Frustaci  2 , Andrea Visentin  3 , Candida Vitale  4 , Michele Bartoletti  5 , Chiara Oltolini  6 , Emanuela Zappulo  7 , Malgorzata Mikulska  8
Affiliations
Review

Severe infections in patients with chronic lymphocytic leukemia included in trials investigating BTK and BCL2 inhibitors

Francesca R Mauro et al. Crit Rev Oncol Hematol. 2024 Sep.

Abstract

Bruton tyrosine kinase inhibitors (BTKi) and the BCL-2 inhibitor venetoclax have significantly improved the prognosis of patients with chronic lymphocytic leukemia (CLL). However, the incidence of severe infections in patients receiving these agents needs to be better understood. Our review aimed to provide an overview of grade ≥3 infections in patients with CLL who received BTKi and venetoclax-based therapy in prospective trials. Infection rates were influenced by the age of patients and the duration of follow-up. For treatment-naive (TN) patients receiving BTKi, infection rates ranged between 11.4 % and 27.4 % and were close to 30 % in relapsed/refractory (R/R) patients. TN and R/R patients receiving fixed-duration venetoclax-based treatments showed variable rates, with maximum values around 20 %. Opportunistic and fatal infections were uncommon. In conclusion, infections remain a concern in patients with CLL receiving targeted agents. A better definition of factors increasing infection vulnerability could help identify those patients who require infection prophylaxis.

Keywords: BCL2 inhibitors; Chronic lymphocytic leukemia; Infections, BTK inhibitors; Treatment.

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Conflict of interest statement

Declaration of Competing Interest F.R.M.: Funding for research and educational projects from Abbvie, Takeda, Janssen. Member of Advisory Board for AbbVie, Beigene, AstraZeneca, Janssen. A.M.F.: Member of Advisory Board for Janssen, Beigene, AstraZeneca, Abbvie. A.V.: Member of Advisory Board for AbbVie, Beigene, AstraZeneca, Janssen, CSL Behring, Takeda. C.V.: Consultancy fees from Abbvie and Astra Zeneca. M.B.: speaker/advisor fees from MSD, BioMérieux, Gilead, AstraZeneca, Advanz, and Pfizer, all outside the submitted work. C.O.: None. E.Z.: None. M.M.: grant from Gilead paid to the Institution; speaker/advisor fees from Allovir, BioMérieux, Gilead, Janssen, Moderna, Mundipharma and Pfizer, all outside the submitted work.

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