title: Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib.
abstract: Ibrutinib is not known to confer risk for Pneumocystis jirovecii pneumonia (PCP). We observed 5 cases of PCP in 96 patients receiving single-agent ibrutinib, including 4 previously untreated. Clinical presentations included asymptomatic pulmonary infiltrates, chronic cough, and shortness of breath. The diagnosis was often delayed. Median time from starting ibrutinib to occurrence of PCP was 6 months (range, 2-24). The estimated incidence of PCP was 2.05 cases per 100 patient-years (95% confidence interval, 0.67-4.79). At the time of PCP, all patients had CD4 T-cell count >500/μL (median, 966/μL) and immunoglobulin G (IgG) >500 mg/dL (median, 727 mg/dL). All patients underwent bronchoalveolar lavage. P jirovecii was identified by polymerase chain reaction in all 5 cases; direct fluorescence antibody staining was positive in 1. All events were grade ≤2 and resolved with oral therapy. Secondary prophylaxis was not given to 3 patients; after 61 patient-months of follow up, no recurrence occurred. Lack of correlation with CD4 count and IgG level suggests that susceptibility to PCP may be linked to Bruton tyrosine kinase (BTK) inhibition. If confirmed, this association could result in significant changes in surveillance and/or prophylaxis, possibly extending to other BTK inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT01500733 and #NCT02514083.
authors: Medical Oncology Service, National Cancer Institute, and.
authors: Inhye E
authors: IE
authors: Ahn
authors: Office of Patient Safety and Clinical Quality, Clinical Center, National Institutes of Health, Bethesda, MD.
authors: Theresa
authors: T
authors: Jerussi
authors: Lymphoid Malignancy Section, Hematology Branch, and.
authors: Mohammed
authors: M
authors: Farooqui
authors: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and.
authors: Xin
authors: X
authors: Tian
authors: Lymphoid Malignancy Section, Hematology Branch, and.
authors: Adrian
authors: A
authors: Wiestner
authors: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Juan
authors: J
authors: Gea-Banacloche
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D010880:Piperidines; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine