Durable benefit of immunotherapy in metastatic Epstein–Barr virus-positive nasopharyngeal carcinoma with cutaneous metastases (lethalides): a case report and review of the literature

Nasopharyngeal carcinoma (NPC) with cutaneous metastases (lethalides) is an exceedingly rare event associated with an aggressive clinical course and poor prognosis, making the management of plurirefractory disease a significant challenge in the evolving landscape of immunotherapy. Here, we report the case of a 59-year-old male diagnosed with stage IVA Epstein–Barr virus (EBV)-positive non-keratinizing NPC who achieved a complete response after induction chemotherapy and concurrent chemoradiotherapy. Twenty-six months later, the patient developed multifocal cutaneous metastases and locoregional recurrence. Over the course of approximately two and a half years, he received six lines of therapy, including platinum-based regimens, pembrolizumab, and cetuximab-paclitaxel, before enrolling in the phase I/II ABILITY-1 trial, where he received the novel interleukin-2 (IL-2) superkine MDNA11 plus pembrolizumab. Despite transient stabilization, the disease progressed, and the patient died 62 months after initial diagnosis. Throughout his clinical course, plasma EBV DNA acted as a precise real-time surrogate of tumor burden, consistently anticipating radiologic progression. This case underscores the aggressive nature of cutaneous NPC and the pivotal role of serial EBV DNA monitoring in guiding therapeutic transitions. Furthermore, the lack of response to multiple agents, including next-generation IL-2 variants, highlights the profound immune exhaustion in late-stage NPC and emphasizes the urgent need for novel targeted strategies, such as antibody-drug conjugates and adoptive T-cell therapies, in the post-immunotherapy setting.