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

Crit Rev Oncol Hematol. 2024 Sep:201:104408. doi: 10.1016/j.critrevonc.2024.104408. Epub 2024 Jun 14.

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.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase* / antagonists & inhibitors
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Clinical Trials as Topic
  • Humans
  • Infections* / epidemiology
  • Infections* / etiology
  • Leukemia, Lymphocytic, Chronic, B-Cell* / complications
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2* / antagonists & inhibitors
  • Sulfonamides / therapeutic use

Substances

  • Agammaglobulinaemia Tyrosine Kinase
  • Proto-Oncogene Proteins c-bcl-2
  • BTK protein, human
  • Protein Kinase Inhibitors
  • BCL2 protein, human
  • venetoclax
  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • Antineoplastic Agents