Advertisement

Invasive Pulmonary Aspergillosis Complicated by Carbapenem-Resistant Pseudomonas aeruginosa Infection During Pembrolizumab Immunotherapy for Metastatic Lung Adenocarcinoma: Case Report and Review of the Literature

  • Chiara Oltolini
  • Marco Ripa
  • Andrea Andolina
  • Elena Brioschi
  • Marta Cilla
  • Giovanna Petrella
  • Vanesa Gregorc
  • Barbara Castiglioni
  • Chiara Tassan Din
  • Paolo Scarpellini
Case Report

Abstract

The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs. These observations lead experts’ opinion to suggest primary anti-Pneumocystis prophylaxis in patients undergoing CTLA-4 and PD-1/PDL1 agents who will receive prednisone 20 mg daily for ≥ 4 weeks. Few data on invasive fungal infections in this context are available. We report here a case of probable invasive pulmonary aspergillosis (p-IPA) complicating first-line immunotherapy with pembrolizumab for metastatic lung cancer that was further aggravated by multidrug-resistant Pseudomonas aeruginosa superinfection of fungal cavities; the patient received concurrent systemic corticosteroid therapy as anti-edema treatment for cerebral metastases. Reviewing literature about Aspergillus diseases in subjects receiving CTLA-4 and PD-1 and PDL1-targeted agents, we found three cases of invasive aspergillosis and one case of exacerbation of chronic progressive pulmonary aspergillosis after nivolumab treatment; to the best of our knowledge, this is the first report of p-IPA complicating pembrolizumab immunotherapy. Briefly, in this new setting of biological/targeted drugs, waiting for growing clinical experience, we recommend a high level of alertness in diagnosing any infectious complications.

Keywords

Pembrolizumab Invasive pulmonary aspergillosis Metastatic lung cancer Programmed death-1/programmed death-1 ligand-targeted agents Opportunistic infections 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, formal consent in not required.

References

  1. 1.
    Redelman-Sidi G, Michielin O, Cervera C, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective-immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine 1-phosphate receptor modulators and proteasome inhibitors. Clin Microbiol Infect. 2018;24(Suppl 2):95–107.CrossRefGoogle Scholar
  2. 2.
    De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813–21.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guidelines. Clin Microbiol Infect. 2018;24(Suppl 1):1–38.CrossRefGoogle Scholar
  4. 4.
    Mikulska M, Furfaro E, Del Bono V, et al. Piperacillin/tazobactam seems to be no longer responsible for false-positive results of the galactomannan assay. J Antimicrob Chemother. 2012;67:1746–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Del Castillo M, Romero FA, Argüello E, et al. The spectrum of serious infections among patients receiving immune checkpoint blockade for the treatment of melanoma. Clin Infect Dis. 2016;63(11):1490–3.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Picchi H, Mateus C, Chouaid C, et al. Infectious complications associated with the use of immune checkpoint inhibitors in oncology: reactivation of tuberculosis after anti PD-1 treatment. Clin Microbiol Infect. 2017;24(3):216–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Kyi C, Hellmann MD, Wolchok JD, et al. Opportunistic infections in patients treated with immunotherapy for cancer. J Immunother Cancer. 2014;2:19.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Uchida N, Fujita K, Nakatani K, et al. Acute progression of aspergillosis in a patient with lung cancer receiving nivolumab. Respirol Case Rep. 2018;6(2):e00289.PubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Chiara Oltolini
    • 1
    • 4
  • Marco Ripa
    • 1
    • 3
  • Andrea Andolina
    • 1
    • 3
  • Elena Brioschi
    • 2
  • Marta Cilla
    • 2
    • 3
  • Giovanna Petrella
    • 2
  • Vanesa Gregorc
    • 2
  • Barbara Castiglioni
    • 1
  • Chiara Tassan Din
    • 1
  • Paolo Scarpellini
    • 1
  1. 1.Unit of Infectious Diseases, Division of Immunology, Transplantation and Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly
  2. 2.Department of Medical OncologySan Raffaele Scientific InstituteMilanItaly
  3. 3.University Vita-Salute San RaffaeleMilanItaly
  4. 4.Department of Infectious DiseasesSan Raffaele Scientific InstituteMilanItaly

Personalised recommendations