Jordi Guzman-Casta, Samuel Alejandro Lozano-Valdez, Frida Sophia Trejo-Mendoza, Mariana Cecilia Macías-Flores
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with limited therapeutic options once it reaches metastatic stages. While immune checkpoint inhibitors like avelumab have improved outcomes, achieving a complete and durable response in stage IV disease remains challenging. We report the case of a 75-year-old male diagnosed with stage IV MCC, negative for Merkel cell polyomavirus (MCPyV) and with 1% PD-L1 tumor cell expression, presenting with a primary tumor in the right thigh, a regional inguinal nodal conglomerate, and a distant mediastinal lymph node metastasis. Initial treatment with first-line avelumab resulted in a discordant response, with a near-complete metabolic response of the mediastinal lesion but persistence of the primary tumor. Localized radiotherapy (RT) - 66 Gy in 33 fractions delivered by intensity-modulated radiotherapy (IMRT), encompassing the primary tumor, the inguinal nodal conglomerate, and at-risk regional nodal basins - was subsequently added while avelumab was continued. Following completion of RT and the fourteenth cycle of avelumab, a complete metabolic and morphological response was documented by FDG PET-CT across all disease sites, including the non-irradiated mediastinal node, consistent with an abscopal effect. Treatment was reasonably well tolerated, with grade 3 radiodermatitis and grade 1 radiation cystitis as the only reported adverse events, and no immune-related toxicity. The patient has since maintained a durable remission under surveillance with maintenance RT. This case suggests a potent synergistic interaction between avelumab and RT, potentially mediated by an abscopal effect at the non-irradiated distant site. The strategic combination of these therapies may overcome initial resistance to immunotherapy in advanced MCC, highlighting the need for further clinical investigation into radio-immunotherapy protocols for this malignancy.