Neurotoxicity of antibodies in cancer therapy: A review

The objective of this manuscript is to identify the neurological side effect profile associated with different classes of antibodies used in cancer pharmacotherapy and to estimate the frequency in which these neurotoxicity occurs. A systematic review of the literature was conducted using OVID MEDLINE and EMBASE databases for articles written between January of 2010 till August of 2018. The spectrum of neurotoxicity was searched using expanded terminology, medical subject headings, truncation, spelling variations and database specific controlled vocabulary. 2134 citations were retrieved that were narrowed down to 151 when SORT 1 or SORT 2 critical appraisal tool was applied to articles with human subjects. Meta-analysis using random effect model was done to estimate the prevalence of neurological symptoms per class of antibody described in SORT1 and SORT2 articles. It was found that the most common neurotoxicity per antibody class are as follows; Bi-specific T-cell engagers was headache 38% [35-40%; I² 0%]; anti-CD20, neuropathy, 16% [7-24%, I² 65%]; anti-CD30, neuropathy 57% [46-68%, I² 72%]; anti-CD52, neuropathy 5-15%; anti-CTL4, headache 12% [7-16%, I² 49%]; anti-EGFR, headache 25% [11-38%, I² 92%]; anti-Her2, neuropathy 33% [18-49%, I² 98%]; anti-PD1 and PDL1, headache 3% [2-5%, I² 85%]; and anti-VEGF, headache 25% [16-35%, I² 73%]. Therefore, all classes of antibodies used in cancer pharmacotherapy have associated neurotoxicity with a wide spectrum of effects afflicting the nervous system as a whole. The specific side effects and the frequency at which they occur differ per class of antibody. Broader and more severe symptoms were noted to effect patients with preexisting brain lesions.