Delaying the use of high-dose melphalan with stem cell rescue in multiple myeloma is ready for prime time

Dickran Kazandjian, Ola Landgren

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The significant advances made in the treatment of multiple myeloma (MM) have allowed for a paradigm shift away from the early use of high-dose melphalan with autologous stem cell transplant (HDM-ASCT). In 2015 alone, the US Food and Drug Administration (FDA) approved 4 novel drugs for MM. Novel drugs and regimens have shown unprecedented efficacy, which has increased the tempo of new drug development. Furthermore, the FDA recently approved a diagnostic test to detect minimal residual disease (MRD) that will allow community clinicians to conduct real-time testing of MRD. Most importantly, frontline regimens based on immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have shown a large clinical benefit. The next era has begun, as several 4-drug combinations that include monoclonal antibodies are being evaluated in clinical trials in the attempt to replace HDM-ASCT in the treatment of MM. We and others have therefore questioned the need for early HDM-ASCT, especially in light of the possible complications. HDM-ASCT is associated not only with acute toxicities—cytopenia, infection, and even death— but also an increased risk of developing secondary cancers. This article discusses the historic context of HDM-ASCT, the modern role of HDM-ASCT given the availability of highly sensitive MRD testing, and the likely future of quadruplet treatment. In summary, patients who attain deep responses using IMiD-and PI-based regimens may not require early HDM-ASCT. A delayed approach to this treatment is acceptable, and might be preferred by patients.

Original languageEnglish (US)
Pages (from-to)559-568
Number of pages10
JournalClinical Advances in Hematology and Oncology
Issue number10
StatePublished - Oct 2019
Externally publishedYes


  • ASCT
  • Carfilzomib
  • Daratumumab
  • High-dose melphalan
  • Minimal residual disease
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology


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