Bortezomib-based induction followed by stem cell transplantation in light chain amyloidosis: results of the multicenter HOVON 104 trial

Haematologica. 2019 Nov;104(11):2274-2282. doi: 10.3324/haematol.2018.213900. Epub 2019 Mar 28.

Abstract

This prospective, multicenter, phase II study investigated the use of four cycles of bortezomib-dexamethasone induction treatment, followed by high-dose melphalan and autologous stem cell transplantation (SCT) in patients with newly diagnosed light chain amyloidosis. The aim of the study was to improve the hematologic complete remission (CR) rate 6 months after SCT from 30% to 50%. Fifty patients were enrolled and 72% had two or more organs involved. The overall hematologic response rate after induction treatment was 80% including 20% CR and 38% very good partial remissions (VGPR). Fifteen patients did not proceed to SCT for various reasons but mostly treatment-related toxicity and disease-related organ damage and death (2 patients). Thirty-one patients received melphalan 200 mg/m2 and four patients a reduced dose because of renal function impairment. There were no deaths related to the transplantation procedure. Hematologic responses improved at 6 months after SCT to 86% with 46% CR and 26% VGPR. However, due to the high treatment discontinuation rate before transplantation the primary endpoint of the study was not met and the CR rate in the intention-to-treat analysis was 32%. Organ responses continued to improve after SCT. We confirm the high efficacy of bortezomib-dexamethasone treatment in patients with AL amyloidosis. However, because of both treatment-related toxicity and disease characteristics, 30% of the patients could not proceed to SCT after induction treatment. (Trial registered at Dutch Trial Register identifier NTR3220).

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Bortezomib / therapeutic use*
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunoglobulin Light-chain Amyloidosis / diagnosis
  • Immunoglobulin Light-chain Amyloidosis / mortality
  • Immunoglobulin Light-chain Amyloidosis / therapy*
  • Immunophenotyping
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Biomarkers
  • Bortezomib

Associated data

  • NTR/NTR3220