Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib

Inhye E. Ahn, Theresa Jerussi, Mohammed Farooqui, Xin Tian, Adrian Wiestner and Juan Gea-Banacloche

Key points

  • Treatment with single-agent ibrutinib can increase susceptibility to Pneumocystis jirovecii pneumonia (PCP) in CLL patients.

  • Key components of PCP diagnosis are increased clinical suspicion and adequate sampling with diagnostic bronchoscopy.


Ibrutinib is not known to confer risk for Pneumocystis jirovecii pneumonia (PCP). We observed five cases of PCP in 96 patients treated with single-agent ibrutinib, including four who were previously untreated. Clinical presentations included asymptomatic pulmonary infiltrates, chronic cough and shortness of breath, and the diagnosis was often delayed. The median time from the start of ibrutinib to the 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/uL (median 966/uL) and IgG >500mg/dL (median 727 mg/dL). All patients underwent diagnostic bronchoalveolar lavage. Pneumocystis jirovecii was identified by PCR in all 5 cases; direct fluorescence antibody staining was positive in one. All events were grade ≤2 and resolved with oral anti-Pneumocystis therapy. Secondary prophylaxis was not given to three patients; with a total of 61 patient-months of follow-up no recurrence occurred. The lack of correlation with CD4 count and IgG level suggests the susceptibility to opportunistic infection may be linked to BTK inhibition. If this association is confirmed, significant changes in practice regarding surveillance and/or prophylaxis, possibly extending to other BTK inhibitors, may be appropriate.; NCT01500733, NCT02514083

  • Submitted June 16, 2016.
  • Accepted July 29, 2016.