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Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy
Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, sugg...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426755/ https://www.ncbi.nlm.nih.gov/pubmed/36052251 http://dx.doi.org/10.3389/fonc.2022.932852 |
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author | Ferla, Valeria Antonini, Elena Perini, Tommaso Farina, Francesca Masottini, Serena Malato, Simona Marktel, Sarah Lupo Stanghellini, Maria Teresa Tresoldi, Cristina Ciceri, Fabio Marcatti, Magda |
author_facet | Ferla, Valeria Antonini, Elena Perini, Tommaso Farina, Francesca Masottini, Serena Malato, Simona Marktel, Sarah Lupo Stanghellini, Maria Teresa Tresoldi, Cristina Ciceri, Fabio Marcatti, Magda |
author_sort | Ferla, Valeria |
collection | PubMed |
description | Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy. Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10(−5) either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods. While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10(−5), hence qualifying as an alternative effective tool for MRD monitoring in MM. Here, we will review state-of-the-art methods for MRD assessment by NGS. We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy. Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making. In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10(−5). Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM. |
format | Online Article Text |
id | pubmed-9426755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94267552022-08-31 Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy Ferla, Valeria Antonini, Elena Perini, Tommaso Farina, Francesca Masottini, Serena Malato, Simona Marktel, Sarah Lupo Stanghellini, Maria Teresa Tresoldi, Cristina Ciceri, Fabio Marcatti, Magda Front Oncol Oncology Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy. Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10(−5) either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods. While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10(−5), hence qualifying as an alternative effective tool for MRD monitoring in MM. Here, we will review state-of-the-art methods for MRD assessment by NGS. We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy. Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making. In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10(−5). Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM. Frontiers Media S.A. 2022-08-16 /pmc/articles/PMC9426755/ /pubmed/36052251 http://dx.doi.org/10.3389/fonc.2022.932852 Text en Copyright © 2022 Ferla, Antonini, Perini, Farina, Masottini, Malato, Marktel, Lupo Stanghellini, Tresoldi, Ciceri and Marcatti https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ferla, Valeria Antonini, Elena Perini, Tommaso Farina, Francesca Masottini, Serena Malato, Simona Marktel, Sarah Lupo Stanghellini, Maria Teresa Tresoldi, Cristina Ciceri, Fabio Marcatti, Magda Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy |
title | Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy |
title_full | Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy |
title_fullStr | Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy |
title_full_unstemmed | Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy |
title_short | Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy |
title_sort | minimal residual disease detection by next-generation sequencing in multiple myeloma: promise and challenges for response-adapted therapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426755/ https://www.ncbi.nlm.nih.gov/pubmed/36052251 http://dx.doi.org/10.3389/fonc.2022.932852 |
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