Clinical and biochemical predictors of response to avelumab in patients with metastatic Merkel Cell Carcinoma (MCC)

Background: Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous malignancy associated with poor prognosis. Immune checkpoint inhibitors (ICIs), including avelumab and pembrolizumab, have recently been approved as first-line treatment for metastatic MCC. Improved clinical outcomes in obese patients treated with ICIs, a phenomenon known as the “obesity paradox,” have been reported across several tumor types. However, data in metastatic MCC patients remain limited, likely due to the rarity of this disease.Patients and methods: This observational, hospital-based study investigated the role of clinical and biochemical markers as potential predictive factors of response to avelumab in patients with metastatic MCC. Patients treated at an Italian referral center for rare tumors between February 2019 and October 2025 were included. Clinicopathological characteristics, BMI, baseline laboratory parameters including neutrophil-to-lymphocyte ratio (NLR) and platelet (PLT) count, and response to avelumab were analyzed using prospectively collected data from an MCC system database.Results: A total of 41 patients were included. Pre-treatment BMI ≥ 30 was significantly associated with longer progression-free survival (PFS) compared with BMI < 30 [BMI < 30 Group: median PFS, 5 months (95% CI: 3.0 – 22.0); BMI ≥ 30 Group: median PFS, not reached; p=0.031]. The multivariable Cox regression model confirmed these observations. Conclusion: To our knowledge, this study represents one of the first investigations evaluating the predictive role of BMI in patients with metastatic MCC treated with first-line avelumab. Our findings are consistent with clinical observations of improved outcomes in obese patients receiving ICIs across multiple tumor types. Advanced age, baseline immune impairment, and obesity-associated “inflammaging” may represent key factors influencing antitumor immune responses in patients with this rare clinical entity.