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. 2021 Nov:158:208-216.
doi: 10.1016/j.ejca.2021.05.041. Epub 2021 Aug 25.

Immune checkpoint inhibitor-associated sarcoidosis: A usually benign disease that does not require immunotherapy discontinuation

Noémie Chanson  1 , Manuel Ramos-Casals  2 , Xerxes Pundole  3 , Karijn Suijkerbuijk  4 , Milton José de Barros E Silva  5 , Merav Lidar  6 , Karolina Benesova  7 , Jan Leipe  8 , Nihan Acar-Denizli  9 , Pauline Pradère  10 , Jean-Marie Michot  11 , Anne-Laure Voisin  12 , Maria E Suárez-Almazor  13 , Timothy R D Radstake  4 , Virginia Fernandes Moça Trevisani  14 , Hendrik Schulze-Koops  7 , Audrey Melin  15 , Caroline Robert  15 , Xavier Mariette  16 , Robert P Baughman  17 , Olivier Lambotte  18 ; ICIR; Coordination; Co-Convenors; Steering Committee; Research Fellows; Data Scientist
Collaborators, Affiliations

Immune checkpoint inhibitor-associated sarcoidosis: A usually benign disease that does not require immunotherapy discontinuation

Noémie Chanson et al. Eur J Cancer. 2021 Nov.

Abstract

Objective: To analyse the clinical patterns of sarcoidosis triggered by immune checkpoint inhibitors (ICIs) in patients with cancer.

Patients and methods: The ImmunoCancer International Registry is a big data-sharing multidisciplinary network from 18 countries dedicated to evaluating the clinical research of immune-related adverse events related to cancer immunotherapies.

Results: We identified 32 patients with biopsy-proven sarcoidosis. Underlying cancer included mainly melanoma (n = 24). Cancer immunotherapy consisted of monotherapy in 19 cases (anti-PD-1 in 18 and ipilimumab in 1) or combined ipilimumab + nivolumab in 13. The time median interval between initiation of ICI and sarcoidosis diagnosis was 3 months (range, 2-29 months). The use of combined ICI was associated with a shorter delay in developing sarcoidosis symptoms. The disease was symptomatic in 19 (59%) cases with mostly cutaneous, respiratory and general symptoms. The organs involved included mainly the mediastinal lymph nodes (n = 32), the lungs (n = 11), the skin (n = 10) and the eyes (n = 5). Pulmonary computed tomography studies showed bilateral hilar lymphadenopathy in all cases. There was no severe manifestation. Specific systemic therapy was required in only 12 patients (37%): oral glucocorticoids in 9, and hydroxychloroquine in 3. ICIs were held in 25 patients (78%) and definitively discontinued in 18 (56%) patients. Seven patients continued ICI treatment with a second flare in one case. In six additional patients, an ICI was reintroduced with no harm, and sarcoidosis relapsed in one of them.

Conclusion: Our study shows that ICI-related sarcoidosis seems to have a specific profile, possibly more benign than that of idiopathic sarcoidosis, and does not necessarily imply ICI discontinuation.

Keywords: Immune checkpoint inhibitor; Immune related adverse event; Immunotherapy; Readministration; Sarcoidosis.

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Conflict of interest statement

Conflict of interest statement Prof Olivier Lambotte was paid for expert testimony by and received consultancy fees from BMS France, MSD and Astra Zeneca; received consultancy fees from Incyte; gave expert testimony for Janssen and received grant from Gilead outside this work. Prof. Robert is a consultant for BMS, Novartis, Roche, Pierre Fabre, Sanofi, Pfizer and MSD. Dr. Leipe reports receiving consultancy and/or speaker fees and/or travel reimbursements unrelated to the topic covered in this publication: Abbvie, BMS, EUSA Pharma, Janssen-Cilag, Gilead, Lilly, Mylan, Novartis, Roche/Chugai, Sanofi UCB. He also has scientific support not related to the topic covered in this publication from Abbott, Gilead, Novartis and federal state Baden-Württemberg. Maria Suarez-Almazor is a consultant for ChemiCentryx, Celgene and Avenue Therapeutics, unrelated to this work. Dr. Robert Baughman has received research grants from Genentech, Actelion, Bayer, aTyr, Belephron, Mallinckrodt and Novartis. He has been a consultant for Riovant, Mallinckrodt and United Therapeutics. He is a member of the speakers’ bureau for Mallinckrodt, Boehringer Ingelheim and United Therapeutics. Dr. J. M. Michot was the principal/sub-investigator of clinical trials in the last five years for Abbvie, Agios, Amgen, Astex, AstraZeneca, Blueprint, BMS, Celgene, Forma, Genentech, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Lilly, Medimmune, MSD, Nektar Therapeutics, Novartis, Oncopeptides AB, Pfizer, Pharmamar, Roche, Sanofi, Seattle Genetics, Sierra Oncology and Xencor. Prof Hendrik Schulze-Koops was paid for expert testimony by and received consultancy fees from AbbVie, Amgen, AstraZeneca, Biogen International, BMS, Boehringer Ingelheim, Celgene, Celltrion, Gilead, GSK, Hospira, Janssen-Cilag, Lilly, Medac, MSD, Merck, Mundipharma, Mylan, Novartis, Pfizer, Sanofi-Aventis, Hexal Sandoz, Roche and UCB. Karijn Suijkerbuijk has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre and Abbvie and received honoraria from Novartis, MSD and Roche. Karolina Benesova has received research grant/research support from (any project) Medical faculty (Olympia Morata Programme) and Foundations commission of University of Heidelberg, Rheumaliga Baden-Württemberg e.V., Abbvie Novartis. She received consultancy and/or speaker fees and/or travel reimbursements (any project) from Abbvie, BMS, Gilead/Galapagos, Janssen, Lilly, MSD, Medac, Mundipharma, Novartis, Pfizer, Roche, and UCB. Dr. Milton Barros was paid for expert testimony by and received consultancy fees from BMS Brazil, MSD and Sanofi and is a member of the speakers' bureau for BMS, MSD and Sanofi. Virginia Fernandes Moça Trevisani, Pauline Pradere, Noémie Chanson, Audrey Melin, Merav Lidar, Pr Xavier Mariette, Manuel Ramos, Nihan Acar, Timothy R.D. Radstake, Xerxes Pundole and Anne-Laure Voison have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

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