title: Clinical outcomes in t(4;14) multiple myeloma: a chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance.
abstract: OBJECTIVE
  To determine whether primary drug resistance or rapid relapse explains the poor prognosis seen in t(4;14)-positive multiple myeloma (MM).
  
  
  METHODS
  A total of 131 patients treated with high-dose therapy (HDT) were assessed, of whom 19 were t(4;14) positive. We examined the presentation features, chemotherapy responsiveness at presentation and to salvage therapies at relapse, and overall survival outcomes.
  
  
  RESULTS
  t(4;14)-positive patients had a predominance of the immunoglobulin A isotype (52.6%) but otherwise baseline characteristics were indistinguishable. After treatment with vincristine, doxorubicin, and dexamethasone or dexamethasone alone, 17 (89.7%) of the 19 patients achieved a partial response and 11 patients (57.9%) demonstrated an additional 50% reduction in paraprotein after HDT. Thus, t(4;14)-positive patients are chemotherapy sensitive; however, early progression was common, with 26% of patients progressing before HDT and a median progression-free survival after HDT of only 14.1 months. At relapse, a resistance to alkylating agents was evident, with no responses (zero of 11 patients) seen with conventional-dose alkylating agents. Salvage regimens using thalidomide and/or dexamethasone achieved at least minimal response in 59% of patients. The duration of response was short, however, with a median of only 4.7 months. The median overall survival after HDT was 24.2 months.
  
  
  CONCLUSIONS
  We conclude that t(4;14)-positive MM is chemotherapy sensitive but rapid relapse occurs. Resistance to alkylating agents is evident at relapse. The development of novel therapeutic agents is required, including the early clinical study of targeted fibroblast growth factor receptor 3 tyrosine kinase inhibitors, which have shown promise in preclinical studies.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Jaksic
authors.forename: Suzanne
authors.initials: S
authors.lastname: Trudel
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Young
authors.initials: Y
authors.lastname: Trieu
authors.forename: Xi
authors.initials: X
authors.lastname: Qi
authors.forename: Joseph
authors.initials: J
authors.lastname: Mikhael
authors.forename: Donna
authors.initials: D
authors.lastname: Reece
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D012008:Recurrence; D016879:Salvage Therapy; D016019:Survival Analysis; D013997:Time Factors; D014178:Translocation, Genetic; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007070:Immunoglobulin A; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin