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This letter presents a case study of a 34-year-old man with relapsing-remitting multiple sclerosis (RRMS) who developed severe progressive multifocal leucoencephalopathy (PML) after using natalizumab. The patient was treated with various interventions, including plasmapheresis and intravenous immunoglobulin, but did not show clinical improvement. However, after receiving pembrolizumab, the patient experienced significant clinical improvement, including improved mobility and cognitive function. The use of pembrolizumab in PML associated with natalizumab is a novel approach, and more research is needed to determine its effectiveness in similar cases. [Extracted from the article]