Abstract
Detecting persistent minimal residual disease (MRD) allows the identification of patients with an increased risk of relapse and death. In this study, we have evaluated MRD 3 months after transplantation in 106 myeloma patients using a commercial next-generation sequencing (NGS) strategy (LymphoTrack®), and compared the results with next-generation flow (NGF, EuroFlow). The use of different marrow pulls and the need of concentrating samples for NGS biased the applicability for MRD evaluation and favored NGF. Despite that, correlation between NGS and NGF was high (R2 = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were longer for undetectable vs. positive patients (NGS: 88.7% vs. 56.6%; NGF: 91.4% vs. 50%; p < 0.001 for both comparisons), which resulted in a 3-year overall survival (OS) advantage (NGS: 96.2% vs. 77.3%; NGF: 96.6% vs. 74.9%, p < 0.01 for both comparisons). In the Cox regression model, NGS and NGF negativity had similar results but favoring the latter in PFS (HR: 0.20, 95% CI: 0.09–0.45, p < 0.001) and OS (HR: 0.21, 95% CI: 0.06–0.75, p = 0.02). All these results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment.
Highlights
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction Multiple myeloma (MM) is a B-cell malignancy where plasma cells arise from a single clone accumulated in the bone marrow1, and usually produce monoclonal immunoglobulins (M-protein or monoclonal component)
Patient and sample selection Patient selection was based on the following criteria: (i) newly diagnosed MM, transplant-candidate patients included in the Spanish GEM2012 clinical trial7, whose clonotypic rearrangements were previously identified, (ii) NGF evaluation performed at diagnosis and followup per protocol, and (iii) enough amount of gDNA available for minimal residual disease (MRD) studies
MRD evaluation has arisen as a very promising tool to predict the outcome of hematologic patients
Summary
Multiple myeloma (MM) is a B-cell malignancy where plasma cells arise from a single clone accumulated in the bone marrow, and usually produce monoclonal immunoglobulins (M-protein or monoclonal component). New agents such as proteasome inhibitors and immunomodulatory drugs, together with autologous stem cell. The International Myeloma Working Group (IMWG) developed new criteria to define MRD negative responses, characterized by the absence of clonal malignant plasma cells in patients with suspected CR, assessed with a sensitivity of at least 10−5—one malignant cell per hundred thousand normal cells; only very sensitive and reliable methods can be applied to detect MRD. MFC allows the identification and quantification of abnormal plasma cells based on an aberrant proteinmarker expression profile displayed by myeloma cells
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