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Clinical aspects

 

Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International ImmunoCancer Registry (ICIR)

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

 

  1. Department of Autoimmune Diseases, ICMiD, Barcelona; Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona; and Department of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain.
  2. Department of Internal Medicine Multi-Organic Diseases, Local Referral Center for Autoimmune Diseases, Saint Eloi Hospital, Montpellier University Hospital, France.
  3. Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  4. APHP Médecine Interne/Immunologie Clinique, Hôpital Bicêtre, Paris, and Université Paris Sud - INSERM U1184 - CEA, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses & Le Kremlin- Bicêtre, France.
  5. Institute of Inflammation and Ageing, University of Birmingham; and National Institute of Health Research Birmingham Biomedical Research Centre and Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  6. Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Subirán, México City, Mexico.
  7. Department of Internal Medicine Multi-Organic Diseases, Local Referral Center for Autoimmune Diseases, Saint Eloi Hospital, Montpellier University Hospital, France.
  8. Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  9. Department of Autoimmune Diseases, ICMiD, Barcelona, Spain.
  10. Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
  11. Department of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  12. Department of Autoimmune Diseases, ICMiD, Barcelona, and Department of Internal Medicine, Hospital CIMA-Sanitas, Barcelona, Spain.
  13. Dept. of Rheumatology, Strasbourg University Hospital, National Centre For Rare Systemic Autoimmune Diseases, CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunologie, Immunopathologie et Chimie Thérapeutique, University of Strasbourg, France.
  14. Department of Rheumatology, Centre Hospitalier Universitaire, Bordeaux, France.
  15. Department of Rheumatology/Clinical Immunology, University Medical Center Utrecht, The Netherlands.
  16. Department of Rheumatology, Centre Hospitalier Universitaire, Bordeaux, France.
  17. Department of Rheumatology/Clinical Immunology, Ludwig-Maximilians-University Munich, Germany.
  18. Department of Rheumatic/Immunologic Diseases, Cleveland Clinic University, Cleveland, OH, USA.
  19. Lupus Clinic, Rheumatology Department, Dubai Hospital, UAE.
  20. Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France.

on behalf of the ICIR

CER12399
2019 Vol.37, N°3 ,Suppl.118
PI 0114, PF 0122
Clinical aspects

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PMID: 31464670 [PubMed]

Received: 06/05/2019
Accepted : 02/07/2019
In Press: 28/08/2019
Published: 28/08/2019

Abstract

OBJECTIVES:
To analyse the worldwide occurrence of sicca/Sjögren’s (SS) syndrome associated with the use of immune checkpoint inhibitors (ICI) in patients with cancer.
METHODS:
The ImmunoCancer International Registry (ICIR) is a Big Data-Sharing multidisciplinary network composed by 40 specialists in Rheumatology, Internal Medicine, Immunology and Oncology from 18 countries focused on the clinical and basic research of the immune-related adverse events (irAEs) related to cancer immunotherapies. For this study, patients who were investigated for a clinical suspicion of SS after being exposed to ICI were included.
RESULTS:
We identified 26 patients (11 women and 15 men, with a mean age at diagnosis of 63.57 years). Underlying cancer included lung (n=12), renal (n=7), melanoma (n=4), and other (n=3) neoplasia. Cancer immunotherapies consisted of monotherapy (77%) and combined regimens (23%). In those patients receiving monotherapy, all patients were treated with PD-1/PD-L1 inhibitors (nivolumab in 9, pembrolizumab in 7 and durvalumab in 4); no cases associated with CTLA-4 inhibitors were identified. The main SS-related features consisted of dry mouth in 25 (96%) patients, dry eye in 17 (65%), abnormal ocular tests in 10/16 (62%) and abnormal oral diagnostic tests in 12/14 (86%) patients. Minor salivary gland biopsy was carried out in 15 patients: histopathological findings consisted of mild chronic sialadenitis in 8 (53%) patients and focal lymphocytic sialadenitis in the remaining 7 (47%); a focus score was measured in 5 of the 6 patients (mean of 1.8, range 1–4). Immunological markers included positive ANA in 13/25 (52%), anti-Ro/ SS-A in 5/25 (20%), RF in 2/22 (9%), anti-La/SS-B in 2/25 (8%), low C3/C4 levels in 1/17 (6%) and positive cryoglobulins in 1/10 (10%). Classification criteria for SS were fulfilled by 10 (62%) out of 16 patients in whom the two key classificatory features were carried out. Among the 26 patients, there were only 3 (11%) who presented exclusively with sicca syndrome without organ-specific autoimmune manifestations. Therapeutic management included measures directed to treat sicca symptoms and therapies against autoimmune-mediated manifestations (glucocorticoids in 42%, second/third-line therapies in 31%); therapeutic response for systemic features was observed in 8/11 (73%). No patient died due to autoimmune involvement.
CONCLUSIONS:
Patients with Sjögren’s syndrome triggered by ICI display a very specific profile different from that reported in idiopathic primary SS, including more frequent occurrence in men, a higher mean age, a predominant immunonegative serological profile, and a notable development of organ-specific autoimmune involvement in spite of the poor immunological profile. The close association found between sicca/Sjögren’s syndrome and primarily PD-1 blockade requires further specific investigation.

Rheumatology Article