Immune checkpoint inhibitors (ICIs) are agents used in immunotherapy to assist the immune system in recognizing and eliminating cancer cells. The primary ICI types used in cancer therapy are programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 monoclonal antibodies. In non–small-cell lung cancer (NSCLC), 4 ICIs have been approved for use: durvalumab, ipilimumab, nivolumab, and pembrolizumab. ICIs are effective, but in some instances the immune-related adverse effects associated with these agents can be serious, including neurologic toxicity. Although this is rare, it can lead to permanent treatment interruption, cancer return or progression, or death.
A recent review published in Clinical Medicine Insights: Oncology summarized 20 case reports of ICI neurologic adverse events (NAEs) in patients with NSCLC. ICI monotherapy has a lower rate of NAEs than combined therapy, which has been estimated to be as high as 12% for nivolumab + ipilimumab therapy. The time to occurrence of NAEs varies, but most happen within 1 to 5 weeks after the first dose is administered. The case reports reviewed in this study revealed later-occurring adverse events in long-term PD-1/PD-L1 ICI responders. This wide time range may affect clinicians’ ability to detect NAEs.
The exact mechanism of how immune-related adverse events occur is unknown, as is the mechanism of how NAEs develop, but autoimmunity is suspected. The peripheral nervous system is twice as likely to be affected by ICI-related neurologic toxicity as the central nervous system. ICI NAEs affecting the peripheral nervous system include Guillain-Barré syndrome, Tolosa-Hunt syndrome, myasthenia gravis, Lambert-Eaton myasthenic syndrome, facial nerve palsies, and chronic immune demyelinating polyneuropathy (acute inflammatory demyelinating polyneuropathy). In the central nervous system, ICI NAEs include meningitis, encephalitis, cerebellitis, multiple sclerosis, transverse myelitis, and posterior reversible encephalopathy syndrome.
The standard treatment for ICI NAEs is steroid administration with intravenous immunoglobulin and plasmapheresis reserved for cases that do not respond well to steroids. The more common ICI NAEs are encephalitis, myasthenia gravis, Guillain-Barré syndrome, and Lambert-Eaton myasthenic syndrome. Encephalitis as a result of ICI use can occur anytime during treatment. Myasthenia gravis is the most common PD-1 inhibitor–related NAE and in the 6 cases of myasthenia gravis evaluated in this review all occurred within 4 treatment cycles. This review also brought forth some clinical questions that could be used for further research studies, namely if ICI-NAE incidence is higher in patients with NSCLC brain metastasis; if ICI use exacerbates preexisting autoimmune symptoms; what the prognosis is of the different NAEs; and how to manage patients who experience a relapse of NAEs.
Although ICI use is safe for the majority of patients with NSCLC, on occasion serious NAEs occur that will require careful monitoring and management.
Source
Cheng K, Wang Y, Zhou Y, et al. Neurological adverse events induced by immune checkpoint inhibitors in non-small cell lung cancer: current perspectives and new developments. Clin Med Insights Oncol. 2021;15:11795549211056261.
