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

Article Figures & Data


  • Figure 1

    Estimated cumulative incidence rate and radiologic presentation of P jirovecii in a CLL patient treated with ibrutinib. (A) The estimated cumulative incidence of PCP in CLL is 4.5% at 1 year on ibrutinib, and 5.6% at 2 years and thereafter. The cumulative incidence of PCP was estimated by considering deaths or early discontinuation of ibrutinib without PCP as competing risk events; otherwise, patients on ibrutinib treatment were censored at the last follow up if no PCP was observed.11 (B-E) Chest CT images of 2 patients are shown who were diagnosed with and treated for PCP while on ibrutinib. The first patient presented with multifocal ground-glass opacificies (B), which significantly improved after treatment of PCP (C). The second patient presented with unilateral nodular infiltrates (D), which resolved after treatment (E).


  • Table 1

    Patient characteristics and clinical presentation of PCP

    Pre-ibrutinibPre-PCP*Presentation and diagnosis of PCPTreatment and outcome
    Patient Age/SexRai stage FISH, IGHVALC/μL ANC/μLCD4/μL CD8/μL CD19/μL NK/μLIgG mg/dL IgM mg/dL IgA mg/dLALC/μL ANC/μLCD4/μL CD8/μL CD19/μL NK/μLIgG mg/dL IgM mg/dL IgA mg/dL
    PCP#1 69/MII Del17p, IGHV-M39 8301593500135 940N/AN/ATT-PCP: 1.9 mo;TMP/SMX 2DS thrice daily, then twice daily for a total of 21 d;
    2140876182920CT: multifocal infiltrates (Figure 1B);Resolved, on prophylaxis (Figure 1C)
    36 76347BAL: PCR+, DFA−, no other pathogen
    PCP#2 68/MI Tri12, IGHV-U58206394871810551727TT-PCP: 23.6 mo;TMP/SMX 2DS thrice daily, then switched to atovaquone 750 mg twice daily for a total of 21 d;
    4420267648202016CT: focal infiltrates;Resolved, no prophylaxis
    510833631BAL: PCR+, DFA−, coexisting Mycobacterium gordonae
    PCP#3 72/MIII Normal, IGHV-U90 83013621013115 690N/AN/ATT-PCP: 1.9 mo;TMP/SMX 2DS twice daily for 18 d;
    18701181861060CT: bilateral infiltrates;Resolved, on prophylaxis
    88 014127BAL: PCR+, DFA−, no other pathogen
    PCP#4 78M§IV Tri12, IGHV-U184 524207493579 310966809TT-PCP: 6.0 mo;TMP/SMX 2DS thrice daily for 14 d;
    12 8702860275650127784CT: bilateral infiltrates;Resolved, no prophylaxis
    177 80021161 825185BAL: PCR+, DFA+; coexisting S aureus and rhino/enterovirus
    PCP#5 70/MIII Tri12, IGHV-U191 31027045141470734615TT-PCP: 11.6 mo;TMP/SMX 2DS thrice daily for 21 d;
    1970134154476035097CT: nodular infiltrates (Figure 1D);Resolved, electively began prophylaxis a year after PCP (Figure 1E)
    164 5974969126BAL: PCR+, DFA−, coexisting Penicillium
    • All patients, except for PCP#4 received ibrutinib as first-line therapy.

    • ALC, absolute lymphocyte count; ANC, absolute neutrophil count; CD4, absolute CD4+ T-cell count; FISH, fluorescence in situ hybridization (Del17p: deletion 17p, Tri12: trisomy 12); IgG, immunoglobulin G; IGHV, Ig heavy chain variable (M: mutated, U: unmutated); NK, natural killer; S aureus, Staphylococcus aureus; TMP/SMX, trimethoprim/sulfamethoxazole; TT-PCP, time from the start of ibrutinib until the first diagnosis of PCP.

    • * ALC and ANC were assessed within 1 week prior to PCP diagnosis. Lymphocyte and Ig subsets were assessed within 2 weeks prior to PCP diagnosis.

    • No lymphocytes subset or Ig data are available between starting ibrutinib and PCP diagnosis for the 2 patients diagnosed at 2 months on single-agent ibritinib.

    • Patient was receiving IVIG replacement.

    • § Patient was previously treated with two lines of therapy prior to ibrutinib. All other patients were previously untreated for CLL prior to ibrutinib.