title: High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis.
abstract: Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain-only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain-only secretion (P < .001), creatinine level 176.8 microM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline-reflecting more aggressive disease-and steeper reductions after therapy identified patients with inferior survival.
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bolejack
authors.forename: Klaus
authors.initials: K
authors.lastname: Hollmig
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pineda-Roman
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Joshua
authors.initials: J
authors.lastname: Epstein
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Abid
authors.initials: A
authors.lastname: Mohiuddin
authors.forename: Yazan
authors.initials: Y
authors.lastname: Alsayed
authors.forename: Gail
authors.initials: G
authors.lastname: Woods
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine*; D001798:Blood Proteins / Q000032:analysis / Q000652:urine; D001853:Bone Marrow / Q000473:pathology; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000652:urine*; D011719:Pyrazines / Q000008:administration & dosage; D051437:Renal Insufficiency / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000652:urine; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D001897:Boronic Acids; D007147:Immunoglobulin Light Chains; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003404:Creatinine; D002945:Cisplatin