Background/Purpose: Immune check point inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) have demonstrated improved survival for multiple cancers but have been associated with immune related adverse events (IRAEs). Granulomatosis have been rarely reported.

Methods: We described patients with granulomatous /sarcoid-like reactions among those receiving anti-PD-1(L1) antibody included in the prospective registry REISAMIC (“Registry of Severe Adverse Events of Immunomodulating Monoclonal Antibodies in Oncology”) between June 2014 and December 2017.

Results: Out of 657 patients under ICIs, 7 cases (1%) developed sarcoid like reactions. ICI regimens included pembrolizumab (4 patients), nivolumab (3 patients) including one in association with ipilimumab, and one combined with an antiangiogenic thyrosine kinase inhibitor. Five patients had melanoma and 2 patients had renal cell carcinoma. Five patients had partial or complete response under immunotherapy while 2 patients had disease progression. Granulomatous reaction occured at a median time of 4 months after beginning the ICI. None patient had preexisting sarcoidosis or autoimmune disease. Granulomatosis involved lymph nodes in 7 cases (including lung in 6 cases), skin in 3 cases , and uveitis in 1 case. Patients were often asymptomatic (mediastinal and hilar lymphadenopathy discovered on radiological evaluation). Three patients developped granulomatous lesions on scars. These clinical presentations were highly suggestive of sarcoidosis diagnosis, confirmed by histology (skin biopsy, pulmonary biopsy in 1 case each, ultrasounded guided endobrachial fine needle aspiration in 3 cases, mediastinoscopy in 1 case). All biopsies were performed in order to avoid cancer progression. No other alternative diagnosis was identified. Bronchoalveolar lavage revealed lymphocytic alveolitis in 2 patients. Pulmonary function tests, cardiac evaluation, and calcemia were normal. Angiotensin converting enzyme levels were in the normal range for 6 out 6 patients. No patient needed corticosteroid treatment while 1 patient required hydroxychloroquine or cutaneous disease. Despite these IRAEs, immunotherapy was continued for 3 patients. Prognostic was good and lymphadenopathy and pulmonary infiltrate and skin granulomas improved in most cases particularly when ICI was stopped.

Conclusion: ICI induced sarcoidosis reactions are rare and most often benign.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/sarcoidosis-induced-by-immune-check-point-inhibitors/