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Infectious complications in CLL/SLL patients receiving Bruton's Tyrosine Kinase inhibitors – systematic review and meta-analysis of randomized controlled trials

S. Buchrits, G. Trieman, Odil Giladi, L. Hofstetter, R. Gurion, Galit Granot, Adi Shacham-Abulafia, P. Raanani et al.

Annals of Hematology, 2025

8,324 participants · 4 citations

Abstract

The development of Bruton Tyrosine Kinase inhibitors (BTKis) has revolutionized the management of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). However, increased infection rates have been reported in patients receiving BTKis in multiple clinical trials. This study aimed to evaluate the risk of infections associated with BTKis compared to other therapeutic regimens in CLL/SLL patients. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. We included trials comparing BTKi-containing regimens (e.g., BTKi alone or combined with anti-CD20 or venetoclax) to other therapeutic regimens, as well as studies comparing different BTKis or BTKi combinations. Primary outcomes were the risk of any infection and grade 3–4 infections. Secondary outcomes included pneumonia, sepsis, septic shock, COVID-19, fungal infections, fatal infections, bacteremia, and febrile neutropenia. Pooled risk ratios (RR) with 95% confidence intervals (CIs) were estimated using fixed or random effects models based on heterogeneity. Eighteen trials encompassing 8,324 patients were included. BTKi-containing regimens, either as monotherapy or combined with anti-CD20 or venetoclax, were not associated with a significantly increased risk of any infection compared to other regimens [BTKi + anti-CD20 or venetoclax: RR 0.93 (95% CI: 0.79–1.09, I2 = 46%), 3 trials; BTKi monotherapy: RR 1.12 (95% CI: 0.94–1.34, I2 = 73%), 3 trials]. Similarly, BTKi monotherapy was…

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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 8,324 participants or records.

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