Review Article | Published:

Minimal residual disease in multiple myeloma: bringing the bench to the bedside

Nature Reviews Clinical Oncology volume 12, pages 286295 (2015) | Download Citation

Abstract

Outcomes for patients with multiple myeloma (MM) have improved substantially in the past decade, with improvements in both progression-free survival and overall survival. Many patients are now achieving a complete response to treatment, and consequently highly sensitive assays are needed for detection of minimal residual disease (MRD) in patients with MM. Results of multicolour flow cytometry and deep-sequencing studies suggest that among patients achieving a complete response, MRD-negative status is associated with significant improvements in progression-free survival and overall survival. Despite the increasing need for MRD testing in patients with MM, considerable heterogeneity in techniques for MRD detection hinders the clinical interpretation of their results. The criteria used to define MRD, strengths and weaknesses of the major types of tests (flow cytometry versus molecular testing), and the optimal sample type (bone marrow aspirate versus peripheral blood) are all unresolved dilemmas in MRD testing. This Review presents an overview of the various techniques for MRD detection in patients with MM. In addition, this article discusses challenges and opportunities for the routine use of MRD testing, possible future directions for clinical trials and implications for drug approval processes.

Key points

  • Outcomes of patients with multiple myeloma have improved substantially in the past decade

  • A large proportion of patients achieve a complete response to current therapies

  • More-sensitive assays for the detection of MRD are required

  • Standardization and guidelines on the use of MRD testing in clinical trials and in the clinic are required

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Acknowledgements

S.M. and M.S.-S. gratefully acknowledge support from the Intramural Research Program of the National Cancer Institute, Bethesda, MD, USA.

Author information

Affiliations

  1. Multiple Myeloma Section, Lymphoid Malignancies Branch, Centre for Cancer Research, National Institutes of Health, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.

    • Sham Mailankody
  2. Flow Cytometry Laboratory, Laboratory of Pathology, National Institutes of Health, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.

    • Maryalice Stetler-Stevenson
  3. Myeloma Service, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

    • Neha Korde
    • , Alexander M. Lesokhin
    • , Nikoletta Lendvai
    • , Hani Hassoun
    •  & Ola Landgren

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Contributions

S.M., N.K., M.S.-S. and O.L. researched the data for the article. S.M. and O.L. wrote the manuscript. All authors contributed to discussions of content, and reviewing and editing the manuscript before submission.

Competing interests

O.L. declares that he has acted as a consultant for BMJ Publishing, Celgene, Millennium, Medscape, and Onyx. The other authors declare no competing interests.

Corresponding author

Correspondence to Ola Landgren.

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DOI

https://doi.org/10.1038/nrclinonc.2014.239

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