Characterization of polyneuropathy in patients receiving enfortumab vedotin (EV) for the treatment of metastatic urothelial carcinoma. 

EV is an antibody-drug conjugate where the antibody binds to nectin-4, an adhesion molecule highly expressed on urothelial carcinomatous cells, and drug monomethyl auristatin E (MMAE) acts as a microtubule inhibitor. Polyneuropathy is reported in 40-50% of treated patients and is the most common side effect necessitating dose reduction. In prior studies, 5% of enrolled subjects had to stop treatment due to polyneuropathy. Sensory polyneuropathy was reported three times more common than motor polyneuropathy. Neuropathy was primarily characterized on clinical grounds, with absence of electrodiagnostic studies and work up for potential other contributing factors. Aim of this study is to further describe polyneuropathy based on detailed neurological examination, electrodiagnostic testing and labs for assessment of any other contributing factors.  

This is a retrospective case series study. Patients treated with EV were referred for neurological evaluation at onset of neuropathy symptoms and underwent detailed neurological history, examination, electrodiagnostic testing and serological testing for other potential contributors for neuropathy. Data will be collected from 10 patients who were followed at the University of California, Irvine neuromuscular clinic from January 2018 to September 2022.

Neuropathy types included length-dependent and non-length-dependent sensory and sensorimotor neuropathy. Contributing factors other than EV exposure were identified in some patients (e.g. vitamin B12 deficiency) and correction resulted in improvement in neuropathy with allowance for continuation of chemotherapy. Dose reduction or treatment “holiday” was done at the discretion of the treating oncologist and resulted in stabilization of symptoms in some. Descriptions of polyneuropathy subtypes, diagnostic work up, treatment and follow up will be presented.

Our cohort provides details on the variability of neuropathy seen in patients treated with EV and provides insights into the electrophysiology, time course and progression of the neuropathy.