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

Autor:	Ramos-Casals M; 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. mramos@clinic.cat, Maria A; Department of Internal Medicine Multi-Organic Diseases, Local Referral Center for Autoimmune Diseases, Saint Eloi Hospital, Montpellier University Hospital, France., Suárez-Almazor ME; Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lambotte O; 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., Fisher BA; 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., Hernández-Molina G; Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Subirán, México City, Mexico., Guilpain P; Department of Internal Medicine Multi-Organic Diseases, Local Referral Center for Autoimmune Diseases, Saint Eloi Hospital, Montpellier University Hospital, France., Pundole X; Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Flores-Chávez A; Department of Autoimmune Diseases, ICMiD, Barcelona, Spain., Baldini C; Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy., Bingham Iii CO; Department of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Brito-Zerón P; Department of Autoimmune Diseases, ICMiD, Barcelona, and Department of Internal Medicine, Hospital CIMA-Sanitas, Barcelona, Spain., Gottenberg JE; 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., Kostine M; Department of Rheumatology, Centre Hospitalier Universitaire, Bordeaux, France., Radstake TRD; Department of Rheumatology/Clinical Immunology, University Medical Center Utrecht, The Netherlands., Schaeverbeke T; Department of Rheumatology, Centre Hospitalier Universitaire, Bordeaux, France., Schulze-Koops H; Department of Rheumatology/Clinical Immunology, Ludwig-Maximilians-University Munich, Germany., Calabrese L; Department of Rheumatic/Immunologic Diseases, Cleveland Clinic University, Cleveland, OH, USA., Khamashta MA; Lupus Clinic, Rheumatology Department, Dubai Hospital, UAE., Mariette X; 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.
Jazyk:	angličtina
Zdroj:	Clinical and experimental rheumatology [Clin Exp Rheumatol] 2019 May-Jun; Vol. 37 Suppl 118 (3), pp. 114-122. Date of Electronic Publication: 2019 Aug 28.
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu