Severe Cerebellar Syndrome Linked With Durvalumab

Abstract

Durvalumab is a monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with programmed cell death 1 (PD-1) molecules. It has shown significant survival benefits in various cancers as an immune checkpoint inhibitor. With increased usage of this therapy, there are several cases with a predilection for neurological immune-related adverse effects from checkpoint inhibitor neurotoxicity. We identified an index patient with lung cancer treated with durvalumab, who developed disabling ocular and bulbar symptoms and severe truncal ataxia, and found symptomatic benefit with plasmapheresis (PLEX). A 57-year-old African American woman presented with 3 months of oscillopsia, dizziness, scanning speech, and inability to stand and walk due to severe truncal ataxia. She was found to have stage IIIA lung adenocarcinoma. Brain magnetic resonance imaging (MRI) demonstrated abnormal T2-fluid-attenuated inversion recovery sequence (T2/FLAIR) signal in bilateral cerebellar hemispheres with lack of enhancement suggestive of paraneoplastic cerebellar involvement. No distinct paraneoplastic antibody was identified. She received combined pulse-dose steroids and intravenous immunoglobulin (IVIg) with no improvement of cerebellar syndrome. A month later, she started inpatient chemotherapy and concurrent radiation therapy with transient cancer regression. Because of subsequent metastatic spread, durvalumab was initiated. She completed four doses that were complicated by worsening cerebellar symptoms and autoimmune colitis. During durvalumab holiday, she received two courses of five PLEX treatments, 2 months apart, along with vigorous physical and speech therapy. Her neurologic symptoms and functional status improved considerably and continued to improve after treatment. At present time, the patient is largely independent for activities of daily living (ADLs) and uses a walker. Repeated brain MRI revealed resolution of previously seen abnormalities. Checkpoint inhibitors may worsen concomitant paraneoplastic neurologic syndromes that develop in association with malignancies potentially responsive to PD-L1 and PD-1 inhibitors. Meticulous coordination and timing of life-saving immune therapies for cancer with effective immune treatments for an underlying or associated neurological syndrome are essential for best outcomes. J Neurol Res. 2020;10(2):44-47 doi: https://doi.org/10.14740/jnr571