Pneumocystis jirovecii pneumonia and institutional prophylaxis practices in CLL patients treated with BTK inhibitors

Opportunistic infections (OIs), such as Pneumocystis jirovecii pneumonia (PIP), have been reported in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and are an important cause of morbidity and mortality. Currently, there are no international consensus guidelines regarding the use of antimicrobial prophylaxis for OIs, and in particular PJP, in CLL patients treated with Bruton tyrosine kinase inhibitors (BTKi's). We evaluated the frequency of PJP in CLL patients at our institution who were treated with BTKi's, and assessed the impact of prophylaxis on reducing the risk of PJP. We identified 217 patients treated with BTKi's, consisting of 3 cohorts: 143 patients on either BTKi monotherapy with ibrutinib or acalabrutinib, 17 patients receiving ibrutinib combination therapy with umbralisib as part of a clinical trial, and 57 patients receiving ibrutinib in combination with standard chemotherapy, also as part of a clinical trial. Forty-one percent of patients on BTKi monotherapy received prophylaxis, which was given at the discretion of the treating physician. The prevalence of PIP in all patients not on prophylaxis was 3.4% (3 of 87), and, specifically in BTKi-monotherapy patients not on prophylaxis, the PIP prevalence was 2.4% (2 of 85). PIP prophylaxis was effective, as there were no cases of PJP in patients on prophylaxis (0 of 130). The relatively low prevalence of PJP in our study population suggests that routine prophylaxis may not be indicated in CLL patients on BTKi therapy.