Introduction: Immune checkpoint inhibitors (ICIs) significantly improved the survival of patients with advanced malignancies. However, ICIs are associated with immune-related adverse events (irAEs), which can be severe. Case presentation: Here, we present a 69-year-old male patient with metastatic urothelial carcinoma (mUC). In April 2018, he was treated in the KEYNOTE-672/ECHO-307 trial with pembrolizumab (anti-PD1) plus epacadostat (anti-IDO1). After three cycles, he developed encephalitis with involuntary dyskinesias of the face and extremities. These were recognized as faciobrachial dystonic seizures, suggestive of anti-LGI1 encephalitis provoked by the treatment. Serum autoantibodies against LGI1 were detected prior to treatment initiation and increased at the time of encephalitis, confirming the diagnosis. Pembrolizumab and epacadostat were withheld, and symptoms disappeared after administration of high-dose steroids. Still immunocompromised by long-term steroid taper, the patient developed a primo disseminated HSV-1 infection, complicated by hepatitis with acute liver failure. He recovered after intravenous treatment with acyclovir. Seven months thereafter, he had progressive disease of mUC. After careful consideration, pembrolizumab monotherapy was restarted with low-dose steroids and valacyclovir maintenance. The patient completed 24 months of treatment with pembrolizumab without the occurrence of new irAEs and has a durable tumor response for more than four years (last follow-up November 2025). Conclusions: Treatment with ICIs can lead to durable responses in patients with advanced malignancies but can be complicated by severe neurological irAEs. In selected cases, treatment with ICIs can be re-initiated safely and effectively. The neurological phenotype and type of neuronal antibody may aid clinical decision making. Maintenance therapy with low-dose steroids can be considered to minimize the relapse risk of irAEs.
Rijnders et al. (Thu,) studied this question.