Abstract

Treatment with immune checkpoint inhibitor (ICIs) has changed the therapeutic landscape of tumours, often associated with better prognosis and increased overall survival.However, ICIs can also cause adverse effects, including the CNS (neurological immune-related adverse events [NirAEs]).NirAEs occur in 1%-6% of patients with ICI treatment and often manifest as a heterogeneous presentation including encephalitis, vasculitis, aseptic meningitis and multiple sclerosis-like lesions/demyelinating syndromes, among others.The underlying mechanism of NirAEs is not fully understood; however, blockade of tumoural inhibitory signals, activation of cytotoxic T-cell-mediated response and molecular mimicry between tumour and nonneoplastic cells in the CNS seem to play a potential role.Here, we present a case of durvalumab-induced neurotoxicity in a 78M patient with metastatic small cell carcinoma (lung origin), who developed 6 months after carboplatin, etoposide and durvalumab treatment, a progressive weakness, sensory deficits causing wheel-chair dependence.Spinal cord MRI showed multiple white matter lesions within the posterior columns of the cervical and thoracic spinal cord.The patient died as of deterioration, and the brain with attached spinal cord were received for autopsy.Neuropathologic examination of the brain showed besides evidence of metastatic disease, a diffuse vasculitis (lymphocytic pattern) and encephalitis within the non-neoplastic background brain parenchyma and acute demyelination of the lateral and posterior white matter tracts of the cervical and thoracic spinal cord.Those adverse changes have been previously described with durvalumab treatment, pointing out the importance of recognizing ICI-induced NirAEs, which can be associated, if untreated, with a high morbidity and mortality.