CPC04 Avelumab-induced sarcoidosis during therapy for metastatic Merkel cell carcinoma

Abstract Merkel cell carcinoma (MCC) is a rare, aggressive nonmel­anoma skin cancer with high metastatic potential and a 33% mortality rate, higher than that of melanoma (Eng TY, Boersma MG, Fuller CD et al. Treatment of Merkel cell carcinoma. Am J Clin Oncol 1997; 20: 184–8). Avelumab, an anti-programmed death ligand 1 immune checkpoint inhibitor, has demonstrated durable responses and improved survival in MCC compared with chemotherapy. While generally well tolerated, it can cause immune-related adverse events (Kaufman HL, Russell J, Hamid O et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 2016; 17: 1374–85). We present the first reported case of newly diagnosed sarcoidosis in a patient receiving avelumab for metastatic MCC. A 69-year-old man had membranous glomerulonephritis treated with tacrolimus. He presented with a tender red dermal nodule on the left shin, surrounded by smaller similar lesions. He had multiple palpable lymph nodes. Computed tomography (CT) of the whole body confirmed left aortic, iliac chain and inguinal adenopathy. Biopsy of a left-leg lesion and lymph nodes later confirmed MCC. Following multidisciplinary team discussion, tacrolimus was stopped, and he commenced palliative avelumab for metastatic MCC. After 9 months of avelumab the leg lesions had healed completely. No new MCC lesions or metastases were identified. His renal function and electrolytes were stable. One year into treatment, he developed multiple erythematous papules on his upper chest. Biopsy reported non-necrotizing granulomatous inflammation, in keeping with cutaneous sarcoid. Positron emission tomography (PET)-CT demonstrated bilateral hilar and mediastinal nodal activity. He also had elevated calcium levels of 3.02 mmol L−1. Given these findings, he was diagnosed with sarcoidosis secondary to avelumab. Oral corticosteroids caused the sarcoid lesions to regress and normalized serum calcium levels. Follow-up PET-CT showed thoracic nodal avidity regression. Avelumab was paused for 3 months, then restarted. However, after 1 month, hypercalcaemia and deteriorating kidney function recurred. Avelumab was permanently discontinued on completion of the planned 2-year course of treatment. Immunotherapy-induced sarcoidosis is a rare but recognized immune-related adverse event. We believe this to be the first reported de novo case secondary to avelumab and we could find only a single report of known sarcoidosis reactivation in the literature (Tun Min S, Nordman IIC, Tran HA. Hypercalcaemia due to sarcoidosis reactivation in patient with metastatic Merkel cell carcinoma treated with avelumab. Case Rep Oncol 2019; 12: 621–7). Given the ever-increasing role of immunotherapy to treat advanced skin cancers, clinicians need to be aware of these complications as the incidence is likely to increase.