title: Normalization of free light chain kappa/lambda ratio is a robust prognostic indicator of favorable outcome in patients with multiple myeloma.
abstract: OBJECTIVE
  To clarify the impact of serum free light chain (sFLC) ratio normalization in patients with multiple myeloma (MM) treated with novel agents.
  
  
  METHODS
  Treatment response in 126 consecutive patients over 7 years was assessed by IMWG criteria and sFLC assay.
  
  
  RESULTS
  Thirty-four patients (27%) showed complete response (CR), 37 (29%) very good partial response (VGPR), 39 (31%) partial response (PR), and 16 (13%) stable disease (SD) or less at a median follow-up of 28 months. Fifty-two patients (41%) with sFLC ratio normalization showed superior progression-free survival (PFS) and overall survival (OS) compared to those who did not (3-yr OS, 94% vs. 48%; P < 0.001). This favorable effect of sFLC ratio normalization occurred irrespective of high (>1000 mg/dL) or low (<100 mg/dL) baseline sFLC. Rates of normal sFLC ratio were as follows: CR, 69%; VGPR, 64%; PR, 16%; and SD or less, 0%. OS was significantly superior in patients with than without normal sFCL ratio in respective response groups. Although various factors (advanced age >70, high LDH, ISS stage 3) showed negative prognostic impacts on PFS and OS on univariate analysis, normal sFLC ratio and achievement of CR emerged as the strongest prognostic predictors for longer OS in MM patients on multivariate analysis.
  
  
  CONCLUSIONS
  This study demonstrated the significance of obtaining normal sFLC ratio independent of other clinical variables. Analysis of sFLC ratio could identify the favorable group of patients as well as immunofixation test and support the inclusion of sFLC ratio as part of the response criteria for MM.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Kameda Medical Center, Chiba, Japan.
authors.forename: Kan-Ichi
authors.initials: K
authors.lastname: Iwama
authors.forename: Dai
authors.initials: D
authors.lastname: Chihara
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsuda
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Ugai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugihara
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Nishida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamakura
authors.forename: Masami
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Kosei
authors.initials: K
authors.lastname: Matsue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality*; D011719:Pyrazines / Q000008:administration & dosage; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D001897:Boronic Acids; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide