Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma
Alejandro Medina, Noemí Puig, Juan Flores‐Montero, Cristina Jiménez, María Eugenia Sarasquete, María García‐Álvarez, Isabel Prieto-Conde, Carmen Chillón, Miguel Alcoceba, Norma C. Gutiérrez, Albert Oriol, Laura Rosiñol, Joan Bladé, Mercedes Gironella, Miguel‐Teodoro Hernández, Verónica González‐Calle, María‐Teresa Cedena, Bruno Paiva, Jesús F. San Miguel, Juan José Lahuerta, María‐Victoria Mateos, Joaquín Martínez‐López, Alberto Órfão, Marcos González, Ramón García‐Sánz
Abstract
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 ( R 2 = 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.