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

Aurore Perrot 1 Valérie Lauwers-Cances 2 Paul Corre 3, 4 Nelly Robillard 5 Cyrille Hulin 6 Marie-Lorraine Chrétien 7 Thomas Dejoie 8 Sabrina Maheo 3 Anne-Marie Stoppa 9 Brigitte Pegourie 10 Lionel Karlin 11 Laurent Garderet 12 Bertrand Arnulf 12 Chantal Doyen Nathalie Meuleman 13 Bruno Royer 14 Jean-Richard Eveillard 15 Lotfi Benboubker 16 Mamoun Dib 17 Olivier Decaux 18 Arnaud Jaccard 19 Karim Belhadj 20 Sabine Bréchignac 21 Brigitte Kolb 22 Cécile Fohrer 23 Mohamad Mohty Margaret Macro 24 Paul Richardson 25 Victoria Carlton Martin Moorhead Tom Willis Malek Faham Kenneth C. Anderson Jean-Luc Harousseau 26 Xavier Leleu 27 Thierry Facon 28 Philippe Moreau 29 Michel Attal 30 Herve Avet-Loiseau 3 Nikhil Munshi 31 
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.
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Soumis le : lundi 4 février 2019 - 12:58:38
Dernière modification le : mercredi 23 novembre 2022 - 12:02:09

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Aurore Perrot, Valérie Lauwers-Cances, Paul Corre, Nelly Robillard, Cyrille Hulin, et al.. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood, 2018, 132 (23), pp.2456-2464. ⟨10.1182/blood-2018-06-858613⟩. ⟨hal-02006039⟩



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