EP1.04-04 Pembrolizumab-Induced Fatal Encephalopathy

Abstract

Pembrolizumab is a monoclonal antibody against programmed cell death 1 (PD-1) receptor approved for PD-L1 positive metastatic non-small cell lung cancer (NSCLC). Neurologic adverse events associated with anti-PD-1 antibodies are rare but might be fatal. We report a case of fatal encephalopathy in a patient with metastatic NSCLC treated with pembrolizumab. A 65-year-old former smoker woman with advanced lung adenocarcinoma with a KRASmutation and an intermediate expression of PD-L1 (20-30%) previously treated with combination of carboplatin and pemetrexed started pembrolizumab (200 mg, every three weeks) after disease progression. After the second infusion of pembrolizumab, she presented with seizures and decreased level of consciousness. Concerning neurological examination, the patient was vigil, carried out only simple commands with absence of speech. Additionally, her muscular tonus was increased. Blood tests were unremarkable. Electroencephalogram was consistent with diffuse encephalopathy and also showed frequent epileptiform activity. Cerebral computed tomography and magnetic resonance revealed central nervous system (CNS) multifocal demyelination. Cerebrospinal fluid was acellular with glucose and protein within normal range. Also, microbiologic examination and polymerase chain reaction (PCR) assay for cytomegalovirus, herpes simplex 1 and 2 and John Cunningham (JC) virus were negative. Anti-onconeural antibodies were absent. Systemic corticosteroid therapy (dexamethasone 4 mg, every six hours) was initiated, with no improvement. Best supportive care was decided by a multidisciplinary team and patient died one month after admission. After excluding other causes for encephalopathy as paraneoplastic syndrome, CNS infection and metastasis, temporal association with pembrolizumab administration made us suspect of an adverse event of this drug. A case of pembrolizumab-induced encephalopathy was reported in advanced NSCLC, after two doses administration and the patient recovered after high dose corticosteroids. However, another case of nivolumab-induced encephalopathy in advanced renal cell carcinoma was fatal, even with drug discontinuation and high dose corticosteroid therapy. Although anti-PD-1 rarely cause encephalopathy, our case highlights not only its occurrence but also shows that it may be rapidly progressive and irreversible. As this entity probably represents an autoimmune process due to PD-1 block, its course is impossible to predict.