Session 2 - Immune mediated neuropathies associated with cancer

Neurological complications of immune checkpoint inhibitors

Aisling CARR (Londres)

Abstract soon available

How to manage neurological complications of ICI and CIDP associated with cancer

Cécile CAUQUIL (Le Kremlin-Bicêtre)

Immune checkpoint inhibitors (ICI) are becoming the standard treatment in many tumor types, with positive results on tumor control but with new toxicities presenting as auto-immune disorders. These immune related adverse events (irAE) have been described and specific guidelines regarding their management have been published. For neurological complications, they offer algorithms for the most frequent irAE including encephalitis, aseptic meningitis, myasthenia gravis, myelitis, neuropathy and inflammatory demyelinating polyneuropathy. Once the irAE identified, and after ruling out differential diagnosis, management relies on immunotherapy withdrawal, treatment with corticosteroids, including in situations unresponsive to steroids such as Guillain Barré syndrome, and close monitoring. The dose of steroids and associated treatments will vary according to severity grade assessed by common terminology criteria for adverse events (CTCAE), mortality rate and by analogy with auto-immune diseases. There are increasing cases of steroid-refractory irAE among which some neurological irAE. Plasmapheresis and/or IVIg have been used and are recommended as second line treatment in most neurological steroid-refractory irAE. Immunosuppressive drugs, inhibiting specific pathways of the acute phase of inflammation, such as anti-TNFα, anti-IL1 or IL6, anti-CD 20, anti-integrin have been tested in some irAE and could be therapeutic options in neurological irAE. The management of these complex neurological irAE requires a good collaboration between oncologists, immunologists and neurologists, with quick assessment, close monitoring and board discussions. In the near future, there will be increasing neurological AE with the widespread of ICI treatment and the emergence of novel anti-tumoral agents, of which neurologists should be aware.

Chronic inflammatory demyelinating polyneuropathy (CIDP) can be associated with malignancy and sometimes lead to the diagnosis of the latter. Classically associated with lymphoma, CIDP has also been reported with solid tumors. Atypical neurological features, general symptoms, abnormal blood testing should prompt for additional testing to detect malignancy. Management relies on one hand on with specific treatment of malignancy with chemotherapy.  In the setting of lymphoma, CIDP can be the sole indication of anti-tumoral treatment such as in Waldenstrom macroglubulinemia. On the other hand immunomodulatory treatments such as IVIg, plasmapheresis or steroids are often necessary and prove to be effective in most cases.

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