title: New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes.
abstract: OBJECTIVE
  To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population.
  
  
  METHODS
  We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed.
  
  
  RESULTS
  There was a strong correlation between the extent of reduction of amyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L), partial response (dFLC decrease > 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation.
  
  
  CONCLUSIONS
  This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials.
authors.affiliation: Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Wechalekar
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Raymond
authors.initials: R
authors.lastname: Comenzo
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000097:blood* / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D003907:Dexamethasone; D008558:Melphalan