Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase...

Area of Science:

• Oncology
• Infectious Diseases
• Pharmacology

Background:

• Previous studies suggested a potential link between Bruton tyrosine kinase inhibitors (BTKis) and invasive fungal infections (IFIs).
• Estimates of IFI frequency in patients with chronic lymphocytic leukemia (CLL) treated with BTKis were previously lacking.
• BTKis are now a first-line therapy for CLL, necessitating a clear understanding of associated risks.

Purpose of the Study:

• To characterize the prevalence of IFIs in patients with CLL.
• To quantify the risk of IFIs associated with BTKi use in CLL patients.
• To identify specific types of IFIs that may be elevated with BTKi therapy.

Main Methods:

• A retrospective analysis of adult patients with CLL was conducted using the TriNetX global research network database.
• A case-control study with propensity score matching was employed to compare IFI events between BTKi users and non-users.
• Analyses were adjusted for age, sex, ethnicity, and other clinical risk factors for IFIs.

Main Results:

• Among 5358 matched CLL patients, the 5-year incidence of IFIs was 4.6% with BTKi use versus 3.5% without.
• Approximately 1% of CLL patients developed an IFI while on a BTKi.
• Adjusted analyses revealed elevated rates of *Pneumocystis jirovecii* pneumonia (PJP) (0.5% vs 0.3%) and invasive candidiasis (3.5% vs 2.7%) with BTKi use.

Conclusions:

• BTKi use in CLL patients is associated with an adjusted elevated rate of PJP and invasive candidiasis.
• The overall rates of these IFIs remain low, with a high number needed to harm (120 for candidiasis, 358 for PJP).
• Further studies are needed to stratify IFIs by specific BTKis and identify at-risk patients for preventive interventions.