Sicca/Sjögren Syndrome Triggered by PD-1/PD-L1 Checkpoint Inhibitors: Data from the International ImmunoCancer Registry (ICIR)

Manuel Ramos-Casals ¹, Alexandre Maria ², Maria E. Suárez-Almazor ³, Olivier Lambotte ⁴, Benjamin A. Fisher ⁵, Gabriela Hernandez-Molina ⁶, Philippe Guilpain ², Xerxes Pundole ³, Soledad Retamozo⁷, Alejandra Flores-Chávez ⁸, Chiara Baldini ⁹, Clifton Bingham ¹⁰, Pilar Brito-Zerón ¹¹, Jacques-Eric Gottenberg ¹², Marie Kostine ¹³, Timothy R.D. Radstake ¹⁴, Thierry Schaeverbeke ¹⁵, Hendrik Schulze-Koops ¹⁶, Leonard Calabrese ¹⁷, Munther A Khamashta ¹⁸ and Xavier Mariette ¹⁹, ¹Department of Autoimmune Diseases, ICMiD. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX. Department of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain., Barcelona, Spain, ²Department of Internal Medicine, Multi-Organic Diseases, Local Referral Center for Autoimmune Diseases, Saint Eloi Hospital- Montpellier-1 University, Montpellier Cedex 5, France, Montpellier, France, ³Department of Rheumatology/Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX , USA., Houston, TX, ⁴APHP Médecine Interne/Immunologie Clinique, Hôpital Bicêtre, Paris, France. Université Paris Sud 11 – INSERM U1184 - CEA, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France., Paris, France, ⁵Institute 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, Birmingham, United Kingdom, ⁶Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, ⁷Instituto De Investigaciones En Ciencias De La Salud, Univ. Nacional de Córdoba, Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina., Cordoba, Argentina, ⁸Department of Autoimmune Diseases, ICMiD, Barcelona, Spain., Barcelona, Spain, ⁹Rheumatology Unit, University of Pisa, Italy., Pisa, Italy, ¹⁰Johns Hopkins University, Baltimore, MD, ¹¹Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic. Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain., Barcelona, Spain, ¹²Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, ¹³Department of Rheumatology, Centre Hospitalier Universitaire, Bordeaux, France, Bordeaux, France, ¹⁴Department of Rheumatology/Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Utrecht, Netherlands, ¹⁵FHU ACRONIM, Department of Rheumatology, Centre Hospitalier Universitaire, Bordeaux, France, Bordeaux, France, ¹⁶Department of Rheumatology/Clinical Immunology, Ludwig-Maximilians-University Munich, Munich, Germany., Munich, Germany, ¹⁷Rheumatologic and Immunologic Disease/Cleveland Clinic, Cleveland, OH, ¹⁸King's College London School of Medicine, London, United Kingdom, ¹⁹Center 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

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Checkpoint Inhibitors and registry, SICCA, Sjogren's syndrome

Session Information

Date: Monday, November 11, 2019

Title: 4M119: Sjögrenʼs Syndrome – Basic & Clinical Science (1902–1907)

Session Type: ACR Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: To analyse the worldwide occurrence of sicca/Sjögren (SjS) 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 investigating for a clinical suspicion of SjS 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 PD1/PD1-L inhibitors (nivolumab in 9, pembrolizumab in 7 and durvalumab in 4); no cases associated with CTLA-4 inhibitors were identified. The main SjS-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 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 to 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 SjS 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 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.

Conclusion: Patients with Sjögren syndrome triggered by ICI display a very-specific profile different from that reported in idiopathic primary SjS, 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 (Figure). The close association found between sicca/Sjögren syndrome and primarily PD1 blockade requires further specific investigation.

Disclosure: M. Ramos-Casals, None; A. Maria, None; M. Suárez-Almazor, Bristol-Myers Squibb, 5, Pfizer Inc, 5, Eli Lilly, 5; O. Lambotte, None; B. Fisher, None; G. Hernandez-Molina, None; P. Guilpain, None; X. Pundole, None; S. Retamozo, None; A. Flores-Chávez, None; C. Baldini, None; C. Bingham, Abbvie, 5, AbbVie, 5, BMS, 2, 5, Bristol Meyer Squibb, 2, 5, Bristol Myers-Squibb, 2, 5, Bristol-Myers Squibb, 2, 5, Eli Lilly, 5, Eli/Lilly, 5, Genentech/Roche, 5, Janssen, 5, Janssen Research & Development, LLC, 2, Pfizer Inc, 5, Regeneron/Sanofi, 5, Sanofi/Regeneron, 5; P. Brito-Zerón, None; J. Gottenberg, Abbvie, 8, BMS, 2, 5, Lilly, 5, 8, Pfizer, 2, 5, Roche, 8, Sanofi-Genzyme, 5, 8, UCB, 5, 8; M. Kostine, None; T. Radstake, None; T. Schaeverbeke, BMS, 5, Janssen, 5, Lilly, 5, Nordic Pharma, 5, Novartis, 5, Pfizer, 5, Roche Chugai, 5, Sanofi, 5; H. Schulze-Koops, None; L. Calabrese, AbbVie, 8, Amgen, 5, Bristol-Myers Squibb, 8, Crescendo, 8, Genentech, 8, GlaxsoSmithKline, 5, Horizon, 5, Janssen, 5, 8, Pfizer, 5, Sanofi-Regeneron, 5, UCB, 5, 8; M. Khamashta, None; X. Mariette, Biogen, 2, Bristol-Myers Squibb, 5, GlaxoSmithKline, 5, Janssen, 5, LFB Pharmaceuticals, 5, OSE Immunotherapeutics, 2, Pfizer, 2, 5, UCB Pharma, 5, 8.

To cite this abstract in AMA style:

Ramos-Casals M, Maria A, Suárez-Almazor M, Lambotte O, Fisher B, Hernandez-Molina G, Guilpain P, Pundole X, Retamozo S, Flores-Chávez A, Baldini C, Bingham C, Brito-Zerón P, Gottenberg J, Kostine M, Radstake T, Schaeverbeke T, Schulze-Koops H, Calabrese L, Khamashta M, Mariette X. Sicca/Sjögren Syndrome Triggered by PD-1/PD-L1 Checkpoint Inhibitors: Data from the International ImmunoCancer Registry (ICIR) [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/sicca-sjogren-syndrome-triggered-by-pd-1-pd-l1-checkpoint-inhibitors-data-from-the-international-immunocancer-registry-icir/. Accessed .

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/sicca-sjogren-syndrome-triggered-by-pd-1-pd-l1-checkpoint-inhibitors-data-from-the-international-immunocancer-registry-icir/