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

Martínez‐López, Joaquín; Sánchez-Vega, Beatriz; Barrio, Santiago; Cuenca, Isabel; Ruiz‐Heredia, Yanira; Alonso, Rafael; Rapado, Inmaculada; Carlos, Marin; Mt, Cedena; Paiva, Bruno; Puig, Noemí; Mv, Mateos; Ayala, Rosa; Mt, Hernández; Jiménez, Cristina; Rosiñol, Laura; Martínez, Rafael; Ai, Teruel; Gutiérrez, Norma C.; Ml, Martin-Ramos; Oriol, Albert; Bargay, Joan; Bladé, Joan; Miguel, Jesús F. San; García‐Sanz, Ramón; Jj, Lahuerta

doi:10.1038/leu.2017.58

Cited by 44 publications

(41 citation statements)

References 15 publications

(28 reference statements)

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“…The patient-specific sequences of these PCR products are sequenced at least 10 6 times using high-throughput NGS, which can detect even a tiny amount of clonal sequence in a sample. This method can be used to assess MRD in more than 95% of patients with MM, and relatively inexpensive and rapid MRD detection at the 10 −6 level is possible due to the lack of requirement for patient-specific PCR primers [25][26][27][28][29][30]. Perrot et al used the NGS method to evaluate MRD in BM in the IFM/DFCI 2009 clinical trial, which assessed a combination therapy comprising new drugs (bortezomib + lenalidomide + dexamethasone [VRD]) [31].…”

Section: Next-generation Sequencingmentioning

confidence: 99%

Clinical value of measurable residual disease testing for multiple myeloma and implementation in Japan

Takamatsu

2020

Int J Hematol

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The development of novel therapeutic agents has led to an increase in patients with multiple myeloma (MM) who achieve a complete response (CR). Consequently, a good correlation has been established between the CR rate and progression-free survival, and new methods are needed to stratify CR cases based on the measurable residual disease (MRD) and thus predict prognosis. Previously, multiparameter flow cytometry (MFC), which is rapid and widely available, has been used to assess MRD in patients with MM. Although the EuroFlow next-generation flow method was developed as a highly sensitive and standardized method of MRD detection, the procedure is costly within the current Japanese public medical insurance system. Recently, two Japanese clinical laboratory test companies, SRL and BML, respectively developed new and inexpensive 8-and 10-color single-tube MFC methods intended for the assessment of MRD under the current Japanese public medical insurance system. In this article, I have reviewed the most recent updates on MRD monitoring protocols in Japan and the clinical trials of the use of this parameter in patients with MM.

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Section: Next-generation Sequencingmentioning

confidence: 99%

Clinical value of measurable residual disease testing for multiple myeloma and implementation in Japan

Takamatsu

2020

Int J Hematol

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“…A mature B cell has undergone VDJ recombination. It was presumed that if a certain amount of clonotypic B cells would be present in the tumor, then a specific PCR product corresponding to the rearranged VDJ genotype could be obtained using specific primers described in studies on detection of monoclonality [15,16,[20][21][22][23]. Further, B cell validation will include quantification of DNA with this VDJ genotype, which will reflect the number of clonotypic B cells in the resulting xenograft.…”

Section: Identification Of the Cells From The Culture And Xenograft Amentioning

confidence: 99%

Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

et al. 2019

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Background: We have characterized the human cell line arised from the Epstein-Barr virus (EBV) positive multiple myeloma aspirate subjected to the long-term cultivation. This cell line has acquired the ability to form free-floating spheres and to produce a xenograft upon transplantation into NOD/SCID mice.Methods: Cells from both in vitro culture and developed xenografts were investigated with a number of analytical approaches, including pathomorphological analysis, FISH analysis, and analysis of the surface antigens and of the VDJ locus rearrangement. Results:The obtained results, as well as the confirmed presence of EBV, testify that both biological systems are derived from B-cells, which, in turn, is a progeny of the EBV-transformed B-cellular clone that supplanted the primordial multiple myeloma cells. Next we assessed whether cells that (i) were constantly present in vitro in the investigated cell line, (ii) were among the sphere-forming cells, and (iii) were capable of internalizing a fluorescent TAMRA-labeled DNA probe (TAMRA+ cells) belonged to one of the three types of undifferentiated bone marrow cells of a multiple myeloma patient: CD34+ hematopoietic stem cells, CD90+ mesenchymal stem cells, and clonotypic multiple myeloma cell.Conclusion: TAMRA+ cells were shown to constitute the fourth independent subpopulation of undifferentiated bone marrow cells of the multiple myeloma patient. We have demonstrated the formation of ectopic contacts between TAMRA+ cells and cells of other types in culture, in particular with CD90+ mesenchymal stem cells, followed by the transfer of some TAMRA+ cell material into the contacted cell.

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“…The clinical significance of sequencing-based MRD assessment in MM patients was recently reported in two studies by the same group [51,57]. In particular, the most recent one adopted an in-house deep-sequencing method using the standardized primers developed by the Biomed-2 concerted action to amplify all IGH or IGK sequences in a patient sample [58].…”

Section: Response Assessmentmentioning

confidence: 99%

“…Sequencing-based MRD assessment fulfills almost all the characteristics that the ideal MRD test should possess, and its clinical significance is recently being reported [51,57].…”

Section: Key Issuesmentioning

confidence: 99%

“…In particular, the most recent one adopted an in-house deep-sequencing method using the standardized primers developed by the Biomed-2 concerted action to amplify all IGH or IGK sequences in a patient sample [58]. Differently from the proprietary multiplex PCR entailed by the LymphoSIGHT method, to be performed at centralized laboratories, this approach can be implemented in any laboratory with NGS capability, thus shortening turn-around time, and can be fully automated, and hence easily standardized reducing inter-lab variation [57]. …”

Section: Response Assessmentmentioning

confidence: 99%

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Utilizing next-generation sequencing in the management of multiple myeloma

Lionetti

Neri

2017

Expert Review of Molecular Diagnostics

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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

Cited by 44 publications

References 15 publications

Clinical value of measurable residual disease testing for multiple myeloma and implementation in Japan

Clinical value of measurable residual disease testing for multiple myeloma and implementation in Japan

Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

Utilizing next-generation sequencing in the management of multiple myeloma

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