High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis

N Engl J Med. 2007 Sep 13;357(11):1083-93. doi: 10.1056/NEJMoa070484.

Abstract

Background: High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation has been reported to provide higher response rates and better overall survival than standard chemotherapy in immunoglobulin-light-chain (AL) amyloidosis, but these two strategies have not been compared in a randomized study.

Methods: We conducted a randomized trial comparing high-dose intravenous melphalan followed by autologous hematopoietic stem-cell rescue with standard-dose melphalan plus high-dose dexamethasone in patients with AL amyloidosis. Patients (age range, 18 to 70 years) with newly diagnosed AL amyloidosis were randomly assigned to receive intravenous high-dose melphalan plus autologous stem cells or oral melphalan plus oral high-dose dexamethasone.

Results: Fifty patients were enrolled in each group. The results were analyzed on an intention-to-treat basis, with overall survival as the primary end point. After a median follow-up of 3 years, the estimated median overall survival was 22.2 months in the group assigned to receive high-dose melphalan and 56.9 months in the group assigned to receive melphalan plus high-dose dexamethasone (P=0.04). Among patients with high-risk disease, overall survival was similar in the two groups. Among patients with low-risk disease, there was a nonsignificant difference between the two groups in overall survival at 3 years (58% in the group assigned to receive high-dose melphalan vs. 80% in the group assigned to receive melphalan plus high-dose dexamethasone; P=0.13).

Conclusions: The outcome of treatment of AL amyloidosis with high-dose melphalan plus autologous stem-cell rescue was not superior to the outcome with standard-dose melphalan plus dexamethasone. (ClinicalTrials.gov number, NCT00344526 [ClinicalTrials.gov].).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloidosis / drug therapy
  • Amyloidosis / mortality
  • Amyloidosis / therapy*
  • Combined Modality Therapy
  • Dexamethasone / administration & dosage*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunoglobulin Light Chains
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / administration & dosage*
  • Middle Aged
  • Myeloablative Agonists / administration & dosage*

Substances

  • Immunoglobulin Light Chains
  • Myeloablative Agonists
  • Dexamethasone
  • Melphalan

Associated data

  • ClinicalTrials.gov/NCT00344526