Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis

Abstract

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions.