Real-world outcomes of patients receiving salvage therapies for immune checkpoint inhibitor-resistant Merkel cell carcinoma: a rationale for future clinical trials

Cancer research · Merkel cell carcinoma

Real-world outcomes of patients receiving salvage therapies for immune checkpoint inhibitor-resistant Merkel cell carcinoma: a rationale for future clinical trials

Merkel cell carcinoma (MCC) is a rare, aggressive neuro‑endocrine skin cancer. First‑line immune‑checkpoint inhibitors (ICIs) that block PD‑1/PD‑L1 achieve durable responses in ~40% of patients, but the remaining ~60% progress either as primary or acquired resistance. In this prospective, single‑center cohort of 106 patients with ICI‑resistant MCC who received at least one salvage therapy, median progression‑free survival (PFS) was 9.5 months for acquired resistance versus 4.7 months for primary resistance (p = 0.006). Median disease‑specific survival (DSS) was not reached in the acquired‑resistance group versus 14.3 months (p = 0.006). Among salvage regimens (ICI alone, ICI + radiation, chemotherapy, chemotherapy + ICI), only the combination of ICI and radiation was significantly associated with improved DSS (adjusted hazard ratio = 0.35, 95% CI 0.14–0.91). A minority of patients (14/106) survived >3 years after salvage initiation, typically following customized, multimodal strategies. These data underscore the need for new salvage approaches and support the use of radiation combined with systemic therapy in the ICI‑resistant setting.

These results illustrate that patients with acquired ICI resistance derive longer survival from salvage therapy than those with primary resistance, and that adding radiation to ICI confers a survival advantage. The observation that a subset of patients can achieve durable, long‑term disease control informs future trial designs and supports multidisciplinary treatment strategies in this hard‑to‑treat population.

Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.

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