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Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma

Aurore Perrot, Valerie Lauwers-Cances, Jill Corre, Nelly Robillard, Cyrille Hulin, Marie-Lorraine Chretien, Thomas Dejoie, Sabrina Maheo, Anne-Marie Stoppa, Brigitte Pegourie, Lionel Karlin, Laurent Garderet, Bertrand Arnulf, Chantal Doyen, Nathalie Meuleman, Bruno Royer, Jean-Richard Eveillard, Lotfi Benboubker, Mamoun Dib, Olivier Decaux, Arnaud Jaccard, Karim Belhadj, Sabine Brechignac, Brigitte Kolb, Cecile Fohrer, Mohamad Mohty, Margaret Macro, Paul G. Richardson, Victoria Carlton, Martin Moorhead, Tom Willis, Malek Faham, Kenneth C. Anderson, Jean-Luc Harousseau, Xavier Leleu, Thierry Facon, Philippe Moreau, Michel Attal, Hervé Avet-Loiseau and Nikhil Munshi

Key Points

  • MRD using NGS-identified patients with an excellent outcome in multiple myeloma.

  • MRD should be assessed in every prospective trial, and is a candidate to become a primary end point.

Publisher's Note: There is a Blood Commentary on this article in this issue.

Abstract

The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (<10−6). Data were analyzed from a recent clinical trial that evaluated the role of transplantation in newly diagnosed myeloma patients treated with lenalidomide, bortezomib, and dexamethasone (RVD). MRD negativity was achieved at least once during maintenance in 127 patients (25%). At the start of maintenance therapy, MRD was a strong prognostic factor for both progression-free survival (adjusted hazard ratio, 0.22; 95% confidence interval, 0.15-0.34; P < .001) and overall survival (adjusted hazard ratio, 0.24; 95% confidence interval, 0.11-0.54; P = .001). Patients who were MRD negative had a higher probability of prolonged progression-free survival than patients with detectable residual disease, regardless of treatment group (RVD vs transplant), cytogenetic risk profile, or International Staging System disease stage at diagnosis. These results were similar after completion of maintenance therapy. Our findings confirm the value of MRD status, as determined by NGS, as a prognostic biomarker in multiple myeloma, and suggest that this approach could be used to adapt treatment strategies in future clinical trials.

  • Submitted June 20, 2018.
  • Accepted August 28, 2018.
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