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

ICIR

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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.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalClinical and experimental rheumatology
Volume37
Issue number3
StatePublished - May 1 2019

Fingerprint

Sjogren's Syndrome
Registries
Sialadenitis
Immunotherapy
Neoplasms
Cryoglobulins
Minor Salivary Glands
Information Dissemination
Rheumatology
Therapeutics
Internal Medicine
Allergy and Immunology
Routine Diagnostic Tests
Glucocorticoids
Mouth
Melanoma
Lung Neoplasms

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

@article{60e962b39d8d44c7b09dc3d40641f7d8,
title = "Sicca/Sj{\"o}gren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International ImmunoCancer Registry (ICIR)",
abstract = "OBJECTIVES: To analyse the worldwide occurrence of sicca/Sj{\"o}gren'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 Sj{\"o}gren'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/Sj{\"o}gren's syndrome and primarily PD-1 blockade requires further specific investigation.",
author = "ICIR and Manuel Ramos-Casals and Alexandre Maria and Su{\'a}rez-Almazor, {Mar{\'i}a E.} and Olivier Lambotte and Fisher, {Benjamin A.} and Gabriela Hern{\'a}ndez-Molina and Philippe Guilpain and Xerxes Pundole and Alejandra Flores-Ch{\'a}vez and Chiara Baldini and Clifton Bingham and Pilar Brito-Zer{\'o}n and Gottenberg, {Jacques Eric} and Marie Kostine and Radstake, {Timothy R.D.} and Thierry Schaeverbeke and Hendrik Schulze-Koops and Leonard Calabrese and Khamashta, {Munther A.} and Xavier Mariette",
year = "2019",
month = "5",
day = "1",
language = "English (US)",
volume = "37",
pages = "114--122",
journal = "Clinical and Experimental Rheumatology",
issn = "0392-856X",
publisher = "Clinical and Experimental Rheumatology S.A.S.",
number = "3",

}

TY - JOUR

T1 - Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International ImmunoCancer Registry (ICIR)

AU - ICIR

AU - Ramos-Casals, Manuel

AU - Maria, Alexandre

AU - Suárez-Almazor, María E.

AU - Lambotte, Olivier

AU - Fisher, Benjamin A.

AU - Hernández-Molina, Gabriela

AU - Guilpain, Philippe

AU - Pundole, Xerxes

AU - Flores-Chávez, Alejandra

AU - Baldini, Chiara

AU - Bingham, Clifton

AU - Brito-Zerón, Pilar

AU - Gottenberg, Jacques Eric

AU - Kostine, Marie

AU - Radstake, Timothy R.D.

AU - Schaeverbeke, Thierry

AU - Schulze-Koops, Hendrik

AU - Calabrese, Leonard

AU - Khamashta, Munther A.

AU - Mariette, Xavier

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

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