Re-challenge of immune checkpoint inhibitor after ICI-encephalitis: A case report

Immune-checkpoint inhibitor (ICI) related encephalitis (ICI-IE) is a severe adverse event, associated with high morbidity and mortality and requiring prompt ICI discontinuation. The safety of rechallenge with ICI after initial adverse event is largely unknown and must be considered only after cautiously weighing risks and benefits of resuming treatment. A 66-year-old otherwise healthy female was diagnosed with localized renal cell carcinoma, which was treated with immunotherapy, ipilimumab/ nivolumab. After the second cycle of treatment, she developed subacute progressive personality changes, memory loss and encephalopathy, and was diagnosed with CTCAE grade III immune-related limbic encephalitis. Her chemotherapy regimen with ipilimumab and nivolumab were promptly discontinued and she was treated with seven days of intravenous solumedrol with prolonged oral steroid taper. Four years later, she had recurrent metastatic disease, prompting the decision to pursue palliative immunotherapy with cabozantinib and immune checkpoint rechallenge with Nivolumab. Given her history of ICI-IE, neuroimmunology was consulted to discuss risks of rechallenge with ICI. Over 9 months after initiation of therapy, she remained without recurrence of immune-related adverse events (irAE) related to treatment. We present one of the first reports of successful rechallenge of immune checkpoint inhibition after ICI-IE in the setting of recurrent metastatic renal cell carcinoma. This treatment success may bolster the management options for refractory oncologic disease. Given potential risks associated with ICI rechallenge, it is imperative to employ a multidisciplinary approach with consideration of potential risks and benefits of treatment.