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

Ramos-Casals, Manuel, Maria, Alexandre, Suárez-Almazor, María E, Lambotte, Olivier, Fisher, Benjamin A, Hernández-Molina, Gabriela, Guilpain, Philippe, Pundole, Xerxes, Flores-Chávez, Alejandra, Baldini, Chiara, Bingham Iii, Clifton O, Brito-Zerón, Pilar, Gottenberg, Jacques-Eric, Kostine, Marie, Radstake, Timothy R D, Schaeverbeke, Thierry, Schulze-Koops, Hendrik, Calabrese, Leonard, Khamashta, Munther A and Mariette, Xavier Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International ImmunoCancer Registry (ICIR). Clinical and experimental rheumatology, 37 Sup (3). pp. 114-122. ISSN 0392-856X.

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To analyse the worldwide occurrence of sicca/Sjögren's (SS) syndrome associated with the use of immune checkpoint inhibitors (ICI) in patients with cancer.


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.


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.


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.

Item Type: Article
Subjects: WD Diseases and disorders of systemic, metabolic or environmental origin > WD811 Rheumatology
Divisions: Emergency Services > Neurology
Ambulatory Care > Rheumatology
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Depositing User: Mrs Yolande Brookes
Date Deposited: 30 Aug 2019 12:10
Last Modified: 30 Aug 2019 12:10

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