New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: Impact on survival outcomes

Giovanni Palladini, Angela Dispenzieri, Morie A. Gertz, Shaji Kumar, Ashutosh Wechalekar, Philip N. Hawkins, Stefan Schönland, Ute Hegenbart, Raymond Comenzo, Efstathios Kastritis, Meletios A. Dimopoulos, Arnaud Jaccard, Catherine Klersy, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review

461 Scopus citations

Abstract

Purpose: 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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)4541-4549
Number of pages9
JournalJournal of Clinical Oncology
Volume30
Issue number36
DOIs
StatePublished - Dec 20 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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