title: Characterization of the peripheral neuropathy associated with brentuximab vedotin treatment of Mycosis Fungoides and Sézary Syndrome.
abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is common, frequently limits chemotherapy dosing, and negatively impacts quality of life. The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0, and the Total Neuropathy Score clinical version (TNSc) are both validated scores to quantify peripheral neuropathy (PN), with the TNSc being more sensitive to clinical changes. Mycosis fungoides and Sézary syndrome (MF/SS) are characterized by a chronic course, where current therapies are generally non-curative and treatment toxicities have the potential for significant lasting effects. Brentuximab vedotin (BV) is an antibody-drug-conjugate composed of an anti-CD30 monoclonal antibody linked to the microtubule-disrupting agent, monomethyl auristatin E, with a known associated CIPN. In our phase II clinical trial of BV in MF/SS, 25 (69%) of 36 patients developed PN, with 18 (50%) developing Clinically Significant PN, CTCAE v4.0 grade 2 or higher. The median time to grade 2 PN was 15 weeks (range 0.4-48) after the initial dose. By Kaplan-Meier calculation, the median time to improvement from Clinically Significant PN was 30 weeks from the last BV dose. Seventy-four percent had improvement by 24 months. We found that TNSc scores significantly correlated with CTCAE grade, with Spearman correlation coefficient 0.68 (p < 0.001). By logistic regression, for each 100 mg increase in BV total dose, the likelihood of developing Clinically Significant PN increased by 23% (95% CI 4-46%). Improved monitoring of CIPN associated with BV is of paramount importance in the MF/SS population.
authors.affiliation: Division of Neuro-Oncology, Department of Neurology and Neurological Sciences, Stanford University, 875 Blake Wilbur Drive, CC 2221, Stanford, CA, 94305-5826, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Corbin
authors.affiliation: Department of Dermatology, Stanford University, Stanford, CA, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Nguyen-Lin
authors.affiliation: Department of Dermatology, Stanford University, Stanford, CA, USA.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Dermatology, Stanford University, Stanford, CA, USA.
authors.forename: Ziba
authors.initials: Z
authors.lastname: Rahbar
authors.affiliation: Department of Dermatology, Stanford University, Stanford, CA, USA.
authors.forename: Mahkam
authors.initials: M
authors.lastname: Tavallaee
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Department of Dermatology, University of Wisconsin and The Middleton VA Medical Center, Madison, WI, USA.
authors.forename: Katrin A
authors.initials: KA
authors.lastname: Salva
authors.affiliation: Department of Dermatology, University of Wisconsin and The Middleton VA Medical Center, Madison, WI, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wood
authors.affiliation: Department of Dermatology, Stanford University, Stanford, CA, USA.
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Division of Neuro-Oncology, Department of Neurology and Neurological Sciences, Stanford University, 875 Blake Wilbur Drive, CC 2221, Stanford, CA, 94305-5826, USA. snagpal@stanford.edu.
authors.forename: Seema
authors.initials: S
authors.lastname: Nagpal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000079963:Brentuximab Vedotin; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D012751:Sezary Syndrome / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates; D000079963:Brentuximab Vedotin
keywords: Brentuximab vedotin; Chemotherapy-induced peripheral neuropathy; Mycosis fungoides; Neuropathy; Sézary syndrome; Total neuropathy score