title: Lenalidomide long-term neurotoxicity: Clinical and neurophysiologic prospective study.
abstract: OBJECTIVE
  To evaluate long-term lenalidomide neurotoxicity and correlation with cumulative dose and hematologic response.
  
  
  METHODS
  Nineteen myeloma patients (7 men, mean age 63.2 years) underwent clinical and neurophysiologic assessment at baseline and at 2 (8 patients, group A) or 5 years (11 patients, group B) after starting lenalidomide therapy for relapsed/refractory multiple myeloma. Neuropathy was scored with Total Neuropathy Score clinical version (TNSc). Lenalidomide cumulative dose was correlated with severity of neuropathy and hematologic response.
  
  
  RESULTS
  At enrollment, 7/19 patients (3 in group A, 4 in group B) had neurophysiologic signs of neuropathy secondary to previous chemotherapy, in 2 of them subclinical. Neurophysiologic evidence of sensory axonal neuropathy occurred in 4/8 patients at 2 years follow-up (group A) and in 3/11 patients at 5 years follow-up (group B). Dorsal sural nerve sensory action potential amplitude was the earliest neurophysiologic abnormality. No relevant (≥4) clinical changes were found in TNSc score. Hematologic overall response was 62% in group A and 100% in group B. No correlation was found between lenalidomide cumulative dose and neuropathy or between neuropathy and hematologic response.
  
  
  CONCLUSIONS
  In our study, up to 50% of myeloma patients on long-term lenalidomide therapy developed sensory axonal neuropathy. Reduced dorsal sural nerve sensory action potential amplitude was the first neurophysiologic alteration. Neuropathy was usually subclinical or mild, however. Neurotoxicity was independent of lenalidomide cumulative dose and hematologic response.
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Torre
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Zambello
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cacciavillani
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Campagnolo
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Berno
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salvalaggio
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De March
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Barilà
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Albano
authors.initials: A
authors.lastname: Lico
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Lucchetta
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Ermani
authors.affiliation: From the Department of Neurosciences (C.D.T., M. Campagnolo, A.S., M.L., M.E., C.B.) and the Medicine, Haematology and Clinical Immunology Branch (R.Z., T.B., E.D.M., G.B., A.L.), University of Padova; and CEMES-EMG Lab (M. Cacciavillani), Data Medica Group, Padova, Italy. chiara.briani@unipd.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Briani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy; D020258:Neurotoxicity Syndromes / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D011446:Prospective Studies; D012008:Recurrence; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D012720:Severity of Illness Index; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide