Paraneoplastic myelitis associated with durvalumab treatment for extensive-stage small cell lung cancer

Abstract

Paraneoplastic neurologic syndromes(PNSs) caused by immune checkpoint inhibitors(ICIs) is rare and requires clinicians to differentiate between disease progression and immune-related adverse effects(irAEs). We hereby report the case of immune-related myelitis accompanied by positive paraneoplastic autoantibodies following durvalumab treatment for extensive-stage small cell lung cancer (ES-SCLC). A 70-year-old Chinese woman with ES-SCLC was administered durvalumab with etoposid-platinum(EP) as first-line treatment. Four cycles after treatment with EP plus ICI, she developed immune-related myelitis with positive paraneoplastic autoantibodies (CV2, SOX1, ZIC4). Spinal MRI showed diffuse abnormal signal shadow in the cervicothoracic spinal cord. She was discontinued for chemotherapy, and treated with high-dose steroids, intravenous immunoglobulin and plasmapheresis, maintenance therapy with steroids resulted in a favorable neurologic outcome. This is the first report of durvalumab-related PNSs. We supposed that the development of paraneoplastic myelitis was causally related to immune activation by durvalumab. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of paraneoplastic myelitis.

Keywords: Durvalumab; Immune checkpoint inhibitor; Immune-related adverse effects; Paraneoplastic neurologic syndromes; Programmed cell death ligand protein 1; Small-cell Lung cancer.

Fig. 1

Chest CT scan showed an almost complete tumor response after three cycles of durvalumab treatment. A Before durvalumab treatment. CT plane scan revealed right lower lobe peripheral lung cancer with hilar lymph node metastasis. Simultaneously, CT contrast enhanced imges showed right lower pulmonary artery invasion, right lower pulmonary vein and right atrium tumor thrombus, right adrenal metastasis. B After durvalumab treatment for three cycles. CT lung window revealed Focal necrosis, thin-walled cavity formationthe hilar lymph nodes were significantly reduced. The morphology of hilum of lung returned to normal

Fig. 2

Immune injury of spinal cord was associated with durvalumab treatment. A Spinal magnetic resonance imaging (MRI) showed the swelling and hyperintensity of C7-T3 Segmentsspinal cord The lesions were laterally distributed in transverse section, and no enhancement was found in CE MRI. B Spinal MRI showed improvement after steroid pulse immunoglobulin and plasmapheresis therapy. The atrophy of the affected spinal cord were shown in the late images of follow-up

Fig. 3

The progression of the lung tumor on chest CT were not synchronized with the changes of the cervicothoracic spinal cord on MRI. A After durvalumab treatment for three cycles. The right lower lobe lung cancer were obviously necrosis and formed thin-walled cavity formed, the hilar lymph nodes were significantly reduced. However, MRI of the spinal cord showed swellowed and ongitudinally extensive intramedullary hyperintensity in the cervicothoracic spinal cord. B The cancer progressed after cessation of anti-cancer therapy four months later. However, MRI showed atrophy of myelopathy.lesions of cervicothoracic spinal cord were stable