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Blood. 2018 Dec 6;132(23):2456-2464. doi: 10.1182/blood-2018-06-858613. Epub 2018 Sep 24.

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

Author information

1
Hematology Department, University Hospital, Nancy, France.
2
Epidemiology and Statistics Department, University Hospital, Toulouse, France.
3
Myeloma Genomics Lab University Cancer Institute Toulouse (IUCT)-Oncopole, Cancer Research Center of Toulouse (CRCT), INSERM 1037, Toulouse, France.
4
Université Paul Sabatier, Toulouse, France.
5
Hematology Laboratory, University Hospital, Nantes, France.
6
Hematology Department, University Hospital, Bordeaux, France.
7
Hematology Department, University Hospital, Dijon, France.
8
Biochemistry Laboratory, University Hospital, Nantes, France.
9
Hematology Department, Institut Paoli Calmettes, Marseille, France.
10
Hematology Department, University Hospital, Grenoble, France.
11
Hematology Department, University Hospital, Lyon, France.
12
Hematology Department, Saint-Antoine University Hospital, Paris, France.
13
Hematology Department, Saint-Louis University Hospital, Paris, France.
14
Hematology Department, Centre Hospitalier Universitaire (CHU) Université Catholique de Louvain (UCL) Namur, Yvoir, Belgium.
15
Hematology Department, Institut Jules Bordet (ULB), Brussels, Belgium.
16
Hematology Department, University Hospital, Amiens, France.
17
Hematology Department, University Hospital, Brest, France.
18
Hematology Department, University Hospital, Tours, France.
19
Hematology Department, University Hospital, Angers, France.
20
Hematology Department, University Hospital, Rennes, France.
21
Hematology Department, University Hospital, Limoges, France.
22
Hematology Department, University Hospital, Creteil, France.
23
Hematology Department, University Hospital, Bobigny, France.
24
Hematology Department, University Hospital, Reims, France.
25
Hematology Department, University Hospital, Strasbourg, France.
26
Hematology Department, University Hospital, Caen, France.
27
Hematology Department, Dana-Farber Cancer Institute, Boston, MA.
28
Adaptive Biotechnologies, Seattle, WA.
29
Hematology Department, Clinique du Confluent, Nantes, France.
30
Hematology Department, University Hospital, Poitiers, France.
31
Hematology Department, University Hospital, Lille, France.
32
Hematology Department, University Hospital, Nantes, France; and.
33
Hematology Department, University Hospital, Toulouse, France.

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.

PMID:
30249784
PMCID:
PMC6284215
[Available on 2019-12-06]
DOI:
10.1182/blood-2018-06-858613

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