Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International Immunocancer Registry (ICIR)
(2019) In Clinical and Experimental Rheumatology 37. p.114-122- Abstract
- Objective. 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... (More)
- Objective. 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. Conclusion. 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. © COPYRIGHT CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2019. (Less)
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- author
- Ramos-Casals, Manel ; Olsson, Peter LU and Calabrese, C
- author collaboration
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Durvalumab, Immune checkpoint inhibitors, Nivolumab, Pembrolizumab, Sjögren's syndrome, antinuclear antibody, cevimeline, cryoglobulin, cyclosporine, durvalumab, glucocorticoid, interleukin 10, ipilimumab, La antibody, methylprednisolone, nivolumab, pembrolizumab, pilocarpine, programmed death 1 ligand 1, programmed death 1 receptor, rheumatoid factor, Ro antibody, adult, aged, Article, autoimmune disease, cancer combination chemotherapy, cancer immunotherapy, cancer registry, chordoma, clinical article, colon cancer, dry eye, eye examination, female, histopathology, human, human tissue, kidney cancer, lung cancer, male, melanoma, middle aged, monotherapy, mouth examination, priority journal, retrospective study, salivary gland biopsy, sialoadenitis, Sjoegren syndrome, uterine cervix cancer, xerostomia, immunology, minor saliva gland, register, B7-H1 Antigen, Female, Humans, Male, Middle Aged, Programmed Cell Death 1 Receptor, Registries, Salivary Glands, Minor, Sjogren's Syndrome
- in
- Clinical and Experimental Rheumatology
- volume
- 37
- pages
- 114 - 122
- publisher
- Pacini
- external identifiers
-
- scopus:85071636917
- ISSN
- 1593-098X
- language
- English
- LU publication?
- yes
- id
- d4a97819-f5b1-4eb9-b409-e8be02cd87e2
- alternative location
- https://www.clinexprheumatol.org/abstract.asp?a=14290
- date added to LUP
- 2020-04-22 13:00:15
- date last changed
- 2022-04-18 21:45:47
@article{d4a97819-f5b1-4eb9-b409-e8be02cd87e2,
abstract = {{Objective. 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. Conclusion. 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. © COPYRIGHT CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2019.}},
author = {{Ramos-Casals, Manel and Olsson, Peter and Calabrese, C}},
issn = {{1593-098X}},
keywords = {{Durvalumab; Immune checkpoint inhibitors; Nivolumab; Pembrolizumab; Sjögren's syndrome; antinuclear antibody; cevimeline; cryoglobulin; cyclosporine; durvalumab; glucocorticoid; interleukin 10; ipilimumab; La antibody; methylprednisolone; nivolumab; pembrolizumab; pilocarpine; programmed death 1 ligand 1; programmed death 1 receptor; rheumatoid factor; Ro antibody; adult; aged; Article; autoimmune disease; cancer combination chemotherapy; cancer immunotherapy; cancer registry; chordoma; clinical article; colon cancer; dry eye; eye examination; female; histopathology; human; human tissue; kidney cancer; lung cancer; male; melanoma; middle aged; monotherapy; mouth examination; priority journal; retrospective study; salivary gland biopsy; sialoadenitis; Sjoegren syndrome; uterine cervix cancer; xerostomia; immunology; minor saliva gland; register; B7-H1 Antigen; Female; Humans; Male; Middle Aged; Programmed Cell Death 1 Receptor; Registries; Salivary Glands, Minor; Sjogren's Syndrome}},
language = {{eng}},
pages = {{114--122}},
publisher = {{Pacini}},
series = {{Clinical and Experimental Rheumatology}},
title = {{Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International Immunocancer Registry (ICIR)}},
url = {{https://www.clinexprheumatol.org/abstract.asp?a=14290}},
volume = {{37}},
year = {{2019}},
}