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

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.

SUBMITTER: Perrot A

PROVIDER: S-EPMC6284215 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Perrot Aurore A Lauwers-Cances Valerie V Corre Jill J Robillard Nelly N Hulin Cyrille C Chretien Marie-Lorraine ML Dejoie Thomas T Maheo Sabrina S Stoppa Anne-Marie AM Pegourie Brigitte B Karlin Lionel L Garderet Laurent L Arnulf Bertrand B Doyen Chantal C Meuleman Nathalie N Royer Bruno B Eveillard Jean-Richard JR Benboubker Lotfi L Dib Mamoun M Decaux Olivier O Jaccard Arnaud A Belhadj Karim K Brechignac Sabine S Kolb Brigitte B Fohrer Cecile C Mohty Mohamad M Macro Margaret M Richardson Paul G PG Carlton Victoria V Moorhead Martin M Willis Tom T Faham Malek M Anderson Kenneth C KC Harousseau Jean-Luc JL Leleu Xavier X Facon Thierry T Moreau Philippe P Attal Michel M Avet-Loiseau Hervé H Munshi Nikhil N

Blood 20180924 23

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 ...[more]

PMID: 30249784

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Project description:BackgroundMinimal residual disease (MRD) is a standard measurement for response assessment in multiple myeloma (MM). Despite new treatments, high-risk MM patients continue to have poor prognosis. We evaluated the effect of MRD negativity in high-risk versus standard-risk patients.Patients and methodsWe retrospectively evaluated all consecutive MM patients who underwent routine MRD testing by 1-tube 8-color advanced flow cytometry with 2,000,000 events and sensitivity level 10-5 at our center from 2015 to 2018 after initial therapy. Kaplan-Meier and log-rank test were used to assess survival estimates and differences between study groups.ResultsOne hundred thirty-six patients with MRD testing after initial therapy or autologous stem-cell transplantation were identified. At a median follow-up of 14 months (range, 1-36 months), progression-free survival and overall survival were significantly worse in high-risk versus standard-risk patients. During the study period, 50% of high-risk group had experienced disease progression (relapse and/or death) versus 20% in the standard-risk group (P = .0006). No patients with standard-risk died, but 4 (14%) in the high-risk group did (P = .0007). Regardless of MRD status, high-risk patients had statistically significant worse progression-free survival than standard-risk patients. At median follow-up, those with disease 10% standard-risk/MRD negative; 20% standard-risk/MRD positive; 40% high-risk/MRD negative; and 45% high-risk/MRD positive had either experienced relapse or died (P = .0041). MRD status did not significantly affect overall survival in either group (P = .0914); however, longer follow-up is needed to assess survival.ConclusionGenetic abnormalities remain a powerful prognostic indicator for MM, regardless of MRD status. For newly diagnosed MM patients treated with novel triple-drug initial therapy and frontline autologous stem-cell transplantation, MRD-negative status did not mitigate the poor-prognosis outcomes of high-risk MM patients.

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

Publications

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

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