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The use of immune checkpoint inhibitors in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is unknown. Concerns are particularly about their safety, due to their potential capacity to exacerbate inflammatory symptoms. Further, there is a lack of data about their role in controlling the UBA1 clones. In this clinical case, we report a successful use of cemiplimab in a patient with VEXAS syndrome and a concomitant diagnosis of metastatic squamous cell carcinoma.