Incidence of invasive fungal infections in patients with chronic lymphocytic leukemia receiving ibrutinib within the veteran’s healthcare administration

Abstract

Purpose Ibrutinib is a tyrosine kinase inhibitor that is increasingly prescribed in chronic lymphocytic leukemia (CLL). Invasive fungal infections (IFIs) have been reported early after ibrutinib initiation. Timing of IFIs is within 6 months and commonly reported fungal infections include Cryptococcus, Aspergillus, and Pneumocystis. Currently, there are no recommendations for routine prophylaxis against IFIs in patients receiving ibrutinib for CLL. Objective The objective of this study was to evaluate the incidence of IFIs in patients receiving ibrutinib for CLL in first-line and relapsed/refractory (R/R) settings. Methods This was a retrospective, cohort study of patients diagnosed with CLL and initiated on ibrutinib in the Veterans Health Administration (VHA) from October 1, 2013 to March 31, 2018. Patients were included if diagnosed with a proven or probable IFI from the start date of ibrutinib to 30 days after the last dose of ibrutinib. Results Fourteen out of 1069 patients met inclusion criteria for IFI while on ibrutinib for CLL. All patients included were male with a median age of 78 years. Fifty percent of patients were initiated on ibrutinib within 3 months of last chemotherapy. IFIs occurred within 3 months (50%) and 6 months (71%) of ibrutinib initiation. Seventy-one percent of patients were continued on ibrutinib with concurrent IFI diagnosis. Conclusion The reported IFI incidence of 1.3% is comparable to current estimates of 1.2%. Future studies should examine the relationship of ibrutinib and incidence of IFIs in first-line and R/R settings in addition to identifying clinical risk factors predisposing patients to IFIs.

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents

“…Increased susceptibility to fungal infection has been reported during ibrutinib treatment [ 173 , 174 , 175 ]. However, the incidence of severe invasive fungal infections is relatively low, ranging from 1.2% to 3% of treated patients [ 176 , 177 , 178 , 179 ], and mainly occurs in heavily pretreated patients or those receiving concurrent steroid treatment [ 173 , 177 , 178 ]. Furthermore, treatment with single-agent ibrutinib can increase susceptibility to PJP, even in TN patients [ 180 , 181 ].…”