Checkpoint inhibitors have reshaped the oncology landscape, but their success comes at the price of immune related adverse events (irAEs). Although rare, neurological irAEs are often disabling and in some cases fatal.
We analyzed the clinical data of all patients who were treated with checkpoint inhibitors and were subsequently diagnosed with neurological irAEs in our institute since January 2015. Alternative diagnoses such as progressive disease and infectious causes were ruled out by MRI and cerebrospinal fluid (CSF) cytology and PCR.
Neurological irAEs were diagnosed in six patients. All patients received anti- PD1, in two cases combined with ipilimumab. Three patients were diagnosed with aseptic meningitis, two with encephalitis and one patient with radiculitis. In all cases, there was a remarkable cerebrospinal fluid (CSF) lymphocytosis (70-99%). All six patients were treated with high-dose steroids. Subsequent intravenous immunoglobulins were administered in three patients. All patients experienced improvement of neurological symptoms after immunosuppressive treatment, with complete resolution of symptoms in three patients.
These data illustrate that CSF lymphocytosis is a hallmark of neurological checkpoint inhibitor toxicity and can be used as a diagnostic aid. Since lymphocytic pleiocytosis is not pathognomonic for neurological irAEs, alternative explanations for lymphocytic pleiocytosis such as viral infections should be ruled out. We encourage clinicians to assess leukocyte differentiation in patients with neurological symptoms that are treated with immune checkpoint inhibitors.
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University Medical Center Utrecht.
Has not received any funding.
K.P. Suijkerbuijk: Consulting, Advisory: Bristol-Myers Squibb, MSD; Honoraria (institution): Novartis, Roche. F.Y.F.L. De Vos: AbbVie, BioClin, Novartis. All other authors have declared no conflicts of interest.