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Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. 2018
Aurore Perrot, and
Valerie Lauwers-Cances, and
Jill Corre, and
Nelly Robillard, and
Cyrille Hulin, and
Marie-Lorraine Chretien, and
Thomas Dejoie, and
Sabrina Maheo, and
Anne-Marie Stoppa, and
Brigitte Pegourie, and
Lionel Karlin, and
Laurent Garderet, and
Bertrand Arnulf, and
Chantal Doyen, and
Nathalie Meuleman, and
Bruno Royer, and
Jean-Richard Eveillard, and
Lotfi Benboubker, and
Mamoun Dib, and
Olivier Decaux, and
Arnaud Jaccard, and
Karim Belhadj, and
Sabine Brechignac, and
Brigitte Kolb, and
Cecile Fohrer, and
Mohamad Mohty, and
Margaret Macro, and
Paul G Richardson, and
Victoria Carlton, and
Martin Moorhead, and
Tom Willis, and
Malek Faham, and
Kenneth C Anderson, and
Jean-Luc Harousseau, and
Xavier Leleu, and
Thierry Facon, and
Philippe Moreau, and
Michel Attal, and
Hervé Avet-Loiseau, and
Nikhil Munshi
Hematology Department, University Hospital, Nancy, France.
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.
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