Analyze the spectrum and frequency of neurotoxicity in cancer patients treated with antibodies. 

Immunotherapy is a new tool to treat cancer and it is associated with neurological side effects.  The neurologist needs to be aware of the spectrum and frequency of these for a focused investigation and fast treatment. 

Systematic meta-analysis using MEDLINE an EMBASE to define the spectrum and frequency of neurotoxicity found to be associated with immunotherapy. Keywords searched in articles written after 2010 included; “antibody, monoclonal” or “immunotherapy” and "cancer and neurotoxicity” in addition to the most commonly used classes of antibodies. Data defined the prevalence of treatment-associated neurotoxicity.

The spectrum of side effects and their frequency per class of antibody include: neuropathy 57% [46-68%, I²72%] with anti-CD-30, 33%[18-49%, I²98%] with anti-HER2, 16% (7-24%, I²65%) with anti-CD-20, 5% with anti-CD52; headache 38% [35-40%; I²0] with anti-CD19-CD3 (BiTE), 25% [16-35%, I²71%] with anti-VEGF , 25% [11-38, I²92%] with anti-EGFR, 10% [3-18%,I²53%] with anti-CTL4, 3% [2-5%, I²43%] with anti-PD1/PDL1 ; myalgia/myopathy  26% [12-40, I²98] with anti-HER2, 3% [2-4%, I²37%] with anti-PDL1/PD1. Hypophysitis and Myasthenia Gravis were specific for the classes of anti-CTL4 and anti-PDL1/PD1. Encephalopathy and seizures were always present, but only achieve frequency over 10% in the BiTE  and anti-VEGF classes.  Other toxicities were tremors, strokes, sleep disorders, ataxia, brain edema and radiation necrosis. The spectrum of neurotoxicity in patients with brain lesions (primary tumors or metastasis) as opposed to patients with only systemic cancers, was more broad with higher incidence of central nervous system toxicity. 

Neurotoxicity is a robustly documented side effect of immunotherapy as defined in varying degrees for all antibodies used in cancer pharmacology. This article is the first to detail the prevalence of immunotherapy-associated neurotoxicity by way of meta-analysis.