To report a case of ICI-associated LETM in a patient with non-small-cell lung cancer (NSCLC) treated with nivolumab and ipilimumab, who experienced symptom recurrence after initial improvement, and to contextualize this within available literature.

Immune checkpoint inhibitors (ICIs) are increasingly recognized to cause neurologic immune-related adverse events (irAEs), including longitudinally extensive transverse myelitis (LETM). Although rare, LETM can be severe, and reports of clinical relapse after apparent recovery are emerging. Optimal strategies for prevention of relapse remain uncertain.

We conducted a retrospective chart review of a 67-year-old man who developed 3 weeks of progressive bilateral lower extremity weakness without bowel, bladder, or sensory deficits. MRI spine demonstrated contrast-enhancing T2 hyperintense lesions spanning C6–T4, consistent with LETM. Cerebrospinal fluid revealed lymphocytic pleocytosis and elevated protein, with negative infectious, autoimmune, and paraneoplastic studies. ICIs were discontinued per ASCO irAE guidance, and he received 5 days of high-dose intravenous methylprednisolone with rapid clinical improvement, followed by discharge to rehabilitation without an oral steroid taper. Ten weeks later, he re-presented with similar symptoms; MRI showed no new lesions. He was treated with intravenous immunoglobulin, repeat IV methylprednisolone, and an oral steroid taper.

Initial concern was that absence of a steroid taper contributed to relapse. However, review of 11 published ICI-associated LETM cases identified 7 treated with nivolumab and/or ipilimumab, among whom 4 relapsed despite steroid tapering.

Apparent recovery after short-course corticosteroids in ICI-associated LETM may not represent complete resolution, and relapse can occur with or without a taper. Clinicians should maintain close surveillance for recurrence, particularly within 10–12 weeks after initial recovery. Optimal duration of corticosteroid therapy and escalation strategies remain undefined and require further investigation.