The role of high-dose melphalan with autologous stem-cell transplant in multiple myeloma: is it time for a paradigm shift?

Br J Haematol. 2020 Dec;191(5):692-703. doi: 10.1111/bjh.16764. Epub 2020 Jun 5.


Recent advances in multiple myeloma include numerous approvals of novel therapies with unprecedented efficacy, a rapid and sustained tempo of new drug development, and further refinements to prognostication to include minimal residual disease (MRD) testing and improved risk stratification. The upfront use of immunomodulatory drug and proteasome inhibitor combinations followed by maintenance has resulted in transformative clinical benefit. Four-drug regimens incorporating monoclonal antibodies are reporting unprecedented rates of complete response and MRD negativity in the absence of intensification. In the context of these advances, the added value of high-dose melphalan with autologous stem-cell transplant (HDM-ASCT) is a key question. From a safety standpoint, HDM-ASCT is associated with both acute toxicities that reduce quality of life and long-term toxicities that may limit life expectancy for some patients. The present review discusses the recent advances in induction therapy, the impact of these advances on HDM-ASCT, the evolving role of MRD testing and the short- and long-term risks of HDM-ASCT. Recognising that prospective data remains limited, we suggest that HDM-ASCT not be considered mandatory for eligible newly diagnosed patients who are treated with highly efficacious regimens and achieve deep responses, but rather be held in reserve without early exposure to the clinical and genomic toxicity inherent to this approach.

Keywords: autologous stem cell transplant; high-dose melphalan; multiple myeloma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Melphalan / therapeutic use*
  • Multiple Myeloma / blood
  • Multiple Myeloma / therapy*
  • Neoplasm, Residual
  • Proteasome Inhibitors / therapeutic use*
  • Transplantation, Autologous


  • Immunologic Factors
  • Proteasome Inhibitors
  • Melphalan