Although neurologic adverse events are uncommon with immune checkpoint inhibitor (ICI) therapy, they may take months to occur, are often severe, and commonly result in treatment discontinuation, according to a retrospective analysis.

The study of patients on ICI therapy for skin cancer found that neurologic side effects usually required hospitalization and, in some cases, intensive care. They occurred with both combination ICI therapy and monotherapy.

“Early diagnosis and treatment, including an interdisciplinary team, are essential,” lead researcher Lea Pöschmann, MD, said in a presentation at the European Association of Dermato-Oncology (EADO) Congress 2026, held in Prague.

Moving forward, the field needs a better understanding of why these neurologic events occur, as well as “more effective and specific treatment options,” added Pöschmann of the National Center for Tumor Diseases and University Cancer Centre Dresden in Dresden, Germany.

There’s no doubt that ICI therapy can offer a substantial survival benefit to patients with melanoma. Pöschmann cited the “impressive” outcomes from the CheckMate 067 trial comparing nivolumab with or without ipilimumab vs ipilimumab alone in patients with previously untreated advanced melanoma.

At the same time, she said, “We have to deal with the high incidence of immune-related adverse events, which could involve every organ system and may potentially be irreversible, severe, and fatal.”

Referring to CheckMate, Pöschmann noted that 60% of patients in the combination therapy arm had a grade 3 or 4 treatment-related adverse event, most often gastrointestinal side effects.

When it comes to neurologic adverse events, research has suggested a prevalence of 4%-12% depending on the ICI regimen. While those adverse events, including headache, are frequently mild, there is also the potential for permanent and debilitating neurologic deficits.

For their study, Pöschmann and her colleagues wanted to take a closer look at the symptoms, diagnosis, treatment, and ultimate outcomes of patients who develop neurologic side effects on ICI therapy.

They started with medical records from 1318 patients at one university medical center who were treated with ICIs for skin cancer between 2016 and 2025. Overall, 43 had documented neurologic adverse events — an incidence of 3.3%.

Most patients with adverse events were treated for melanoma (88%); their mean age was 69.5 years, and 60.5% were male.

While the majority of those patients were on combination therapy with nivolumab plus ipilimumab (56%), many (44%) were on ICI monotherapy.

The most common diagnosis, affecting 49% of patients, was encephalitis. Another 28% were diagnosed with peripheral polyneuropathy, and 19% developed meningitis. One quarter of patients were diagnosed with more than one neurologic adverse event.

Often, the study found, those events took time to emerge, with a median onset of 123 days after the start of therapy.

Diagnostic interventions included neurologic examination, radiologic imaging, and laboratory parameters — though, Pöschmann noted, lab tests were “very unspecific,” often failing to look for autoantibodies or other possible causes of neurologic symptoms, such as vitamin B12 deficiency.

In addition, electronystagmography was performed in 33% of patients, electroencephalography in 20%, and lumbar puncture in 46.5%.

As for treatment, all patients received corticosteroids, including high-dose methylprednisolone for encephalitis. Many (30.2%) received additional immunosuppressive treatment, such as intravenous immunoglobulins, infliximab, or mycophenolate mofetil.

Only a minority of patients could be managed on an outpatient basis; 84% were hospitalized, with 7% requiring intensive care. Pöschmann said that for most patients, ICI therapy had to be discontinued or put on hold.

Regarding long-term outcomes, 44% of patients had no lasting toxicity, whereas 47% had chronic neurologic symptoms that eventually improved with immunosuppressive treatment.

Severe long-term toxicity — defined as limiting daily activities and not improving with immunosuppressive treatment — was seen in four patients (9%).

Mirna Šitum, MD, PhD, dermato-oncologist at the University Hospital Center “Sestre milosrdnice” in Zagreb, Croatia, co-chaired the session.

She said the findings underscore the importance of early surveillance for neurologic adverse events in patients on ICI therapy. She also suggested that clinicians have a lower threshold for multidisciplinary neurology workup when patients have potential symptoms of such side effects.

Pöschmann agreed on both points and added that any time patients develop nonspecific symptoms on ICI therapy, clinicians should have the possibility of neurologic involvement on their radar.

The researchers disclosed receiving no funding for the study and having no relevant financial relationships.