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

被引:133
作者
Ahn, Inhye E. [1 ]
Jerussi, Theresa [2 ]
Farooqui, Mohammed [3 ]
Tian, Xin [4 ]
Wiestner, Adrian [3 ]
Gea-Banacloche, Juan [5 ]
机构
[1] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA
[2] NIH, Off Patient Safety & Clin Qual, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA
[3] NHLBI, Lymphoid Malignancy Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA
[4] NHLBI, Off Biostat Res, NIH, Bldg 10, Bethesda, MD 20892 USA
[5] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HIV; OPEN-LABEL; RITUXIMAB; TRIAL; FLUDARABINE; CYCLOPHOSPHAMIDE; BENDAMUSTINE; THERAPY; PHASE-3;
D O I
10.1182/blood-2016-06-722991
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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/mu L (median, 966/mu L) 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.
引用
收藏
页码:1940 / 1943
页数:4
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