Induction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective Clinical Trial

Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. doi: 10.1016/j.bbmt.2015.04.001. Epub 2015 Apr 6.

Abstract

The depth of hematologic response has been shown to correlate with survival and organ responses for patients with light chain (AL) amyloidosis. We conducted a prospective trial of 2 cycles of induction with bortezomib and dexamethasone on a twice a week schedule followed by conditioning with bortezomib and high-dose melphalan (HDM) and autologous stem cell transplantation (SCT). The objectives were hematologic responses, tolerability, and survival. Thirty-five patients were enrolled from 2010 to 2013. Of these, 30 proceeded with SCT, whereas 5 did not because of clinical deterioration during induction (n = 3) or complications after stem cell collection (n = 2). Two patients developed features of an autologous graft-versus-host disease-like syndrome post-SCT, which responded to steroids; no other unusual complications were seen. Treatment-related mortality occurred in 8.5% (3/35). Hematologic responses were achieved by 100% of the 27 assessable patients (63% complete response, 37% very good partial response [VGPR]) who completed the planned treatment. By intention-to-treat, hematologic responses occurred in 77% of patients (49% complete response, 29% VGPR). With a median follow-up of 36 months, the median overall survival and progression-free survival were not reached. In conclusion, incorporating bortezomib into induction and conditioning yielded a high rate of hematologic responses after HDM/SCT in patients with AL amyloidosis.

Keywords: AL amyloidosis; Bortezomib; Induction; Melphalan; Stem cell transplantation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyloidosis / drug therapy*
  • Amyloidosis / mortality
  • Amyloidosis / therapy*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Bortezomib / administration & dosage
  • Bortezomib / therapeutic use*
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunoglobulin Light-chain Amyloidosis
  • Induction Chemotherapy / methods*
  • Male
  • Melphalan / administration & dosage
  • Melphalan / therapeutic use*
  • Middle Aged
  • Prospective Studies
  • Survival Analysis
  • Transplantation Conditioning / methods*

Substances

  • Antineoplastic Agents
  • Bortezomib
  • Melphalan