Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma

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 this, correlation between NGS and NGF was high (R² = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were lower for undetectable vs. positive patients (NGS: 78. vs. 56.96%: P: 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 for achieving better PFS (HR: 0.21, 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.

Alejandro Medina, Noemi Puig, Juan Flores-Montero, Cristina Jimenez, M. Eugenia Sarasquete, Maria Garcia-Alvarez, Isabel Prieto-Conde, Carmen Chillon, Miguel Alcocer, Norma C. Gutierrez, Albert Oriol, Laura Rosinol, Joan Blade, Mercedes Gironella, Miguel T. Hernandez, Veronica Gonzalez-Calle, Maria-Teresa Cederna, Bruno Paiva, Jesus F. San-Miguel, Juan-Jose Lahuerta, Maria-Victoria Mateos, Joaquin Martinez-Lopez, Alberto Orfao, Marcos Gonzalez, Ramon Garcia-Sanz