Publicaciones científicas

Analytical and clinical validation of a novel in-house deep-sequencing method for minimal residual disease monitoring in a phase II trial for multiple myeloma

01-jun-2017 | Revista: Leukemia

J Martinez-Lopez  1 , B Sanchez-Vega  1 , S Barrio  2 , I Cuenca  1 , Y Ruiz-Heredia  1 , R Alonso  1 , I Rapado  1 , C Marin  1 , M-T Cedena  1 , B Paiva  3 , N Puig  4 , M-V Mateos  4 , R Ayala  1 , M-T Hernández  5 , C Jimenez  4 , L Rosiñol  6 , R Martínez  7 , A-I Teruel  8 , N Gutiérrez  4 , M-L Martin-Ramos  1 , A Oriol  9 , J Bargay  10 , J Bladé  6 , J San-Miguel  3 , R Garcia-Sanz  4 , J-J Lahuerta  1

The first step for the cure of multiple myeloma (MM) is to achieve a complete response (CR);1, 2 however, regardless of CR improvement, most patients experience disease progression or relapse in part due to the persistence of low levels of clonal plasma cells after treatment (minimal residual disease (MRD)).3

In addition, many patients who achieve MRD-negative status also relapse, indicating that the sensitivity and specificity of traditional techniques for MRD assessment can be improved.4

At present, multiparameter flow cytometry (MFC), allele-specific oligonucleotide PCR and high-throughput sequencing (NGS) are the three high-sensitivity techniques available for MRD quantification in MM.3, 5, 6

A growing body of evidence strongly suggests that detection of subclinical levels of MRD with this high-sensitivity methods provides powerful independent prognostic information.7, 8 MFC is the most widely available technique with excellent sensitivity and applicability; however, there is variability in sensitivity, panels and performance between laboratories, and requires high level of expertise.9

On the other hand, in previous work, we have shown that NGS of immunoglobulin (IG) rearranged genes is an effective technology to identify and quantify pathological clonal cells in MM with a sensitivity of at least 0.001%.7, 10

However, this NGS technology is a proprietary multiplex PCR that is performed at centralized laboratories increasing the turn-around time for the results. Furthermore, the NGS method for MRD quantification in MM needs additional clinical validation to prove its utility for patient risk stratification, as well as to evaluate the efficacy of different treatment schemes.

CITA DEL ARTÍCULO  Leukemia. 2017 Jun;31(6):1446-1449. doi: 10.1038/leu.2017.58. Epub 2017 Feb 17