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

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.