Complete metabolic response in stage IV Merkel cell carcinoma after combined avelumab and radiotherapy: a case report suggestive of an abscopal effect

Information from the abstract

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.

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