Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma.
Fiche publication
Date publication
septembre 2018
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FOHRER Cécile, Dr CHRETIEN Marie-Lorraine
Tous les auteurs :
Perrot A, Lauwers-Cances V, Corre J, Robillard N, Hulin C, Chretien ML, Dejoie T, Maheo S, Stoppa AM, Pegourie B, Karlin L, Garderet L, Arnulf B, Doyen C, Meuleman N, Royer B, Eveillard JR, Benboubker L, Dib M, Decaux O, Jaccard A, Belhadj K, Brechignac S, Kolb B, Fohrer C, Mohty M, Macro M, Richardson PG, Carlton V, Moorhead M, Willis T, Faham M, Anderson KC, Harousseau JL, Leleu X, Facon T, Moreau P, Attal M, Avet-Loiseau H, Munshi N
Lien Pubmed
Résumé
The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. In order to shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate endpoint in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing. MRD negativity was defined as the absence of tumor plasma cell within 1,000,000 bone marrow cells (<10). 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 to 0.34; P<0.001) and overall survival (adjusted hazard ratio, 0.24; 95%confidence interval, 0.11 to 0.54; P=0.001). 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 versus 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 next-generation sequencing, as a prognostic biomarker in multiple myeloma, and suggest that this approach could be used to adapt treatment strategies in future clinical trials.
Référence
Blood. 2018 Sep 24;: