Response to combined peptide receptor radionuclide therapy and checkpoint immunotherapy with ipilimumab plus nivolumab in metastatic Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine cancer of the skin. For patients who are refractory to immune checkpoint inhibition (ICI), treatment options are limited. Few cases of MCCs with high somatostatin receptor (SSTR) expression were reported to show responses upon SSTR-directed peptide receptor radionuclide therapy (PRRT). A combination of PRRT and ICI has not been reported in MCC to date. A 60-year old man with metastatic MCC, who was primarily resistant to the anti-PD-L1 ICI with avelumab and secondarily resistant to the anti-CTLA4 plus anti-PD-1 ICI therapy with ipilimumab plus nivolumab (IPI/NIVO) with additional RT, presented with multiple bone and lymph node metastases. After confirmation of SSTR expression, the patient was treated with a salvage therapy of additional four doses of IPI/NIVO combined with two cycles of PRRT. Treatment was well tolerated with transient hematoxicity and mild nausea. Re-staging three months after therapy start showed an exceptional good response. This case report demonstrates the feasibility of a combined treatment with IPI/NIVO and PRRT as a salvage option for MCC patients progressing under ICI therapy. Prospective evidence confirming the additive value of combining ICI and radionuclide therapy in a larger cohort is needed.