Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease

Alcoceba, Miguel; Stewart, James P.; García-Alvarez, María; Díaz, Luis G.; Jiménez, Cristina; Medina, Alejandro; Chillón, M. del Carmen; Gazdova, Jana; Blanco, Óscar; Díaz, Francisco J.; Peñarrubia, María J.; Fernández, Silvia; Montes, Carlos; Cabero, Almudena; Caballero, Maria Dolores; García-Sanz, Ramón; González, Marcos; González, David; Tamayo, Pilar; Gutiérrez, Norma Carmen; García-Sancho, Alejandro Martín; Sarasquete, María Eugenia

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBC...

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Autores:	Alcoceba, Miguel, Stewart, James P., García-Alvarez, María, Díaz, Luis G., Jiménez, Cristina, Medina, Alejandro, Chillón, M. del Carmen, Gazdova, Jana, Blanco, Óscar, Díaz, Francisco J., Peñarrubia, María J., Fernández, Silvia, Montes, Carlos, Cabero, Almudena, Caballero, Maria Dolores, García-Sanz, Ramón, González, Marcos, González, David, Tamayo, Pilar, Gutiérrez, Norma Carmen, García-Sancho, Alejandro Martín, Sarasquete, María Eugenia
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2024
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/381200
Acceso en línea:	http://hdl.handle.net/10261/381200
Access Level:	acceso abierto
Palabra clave:	Liquid Biopsy Minimal residual disease Molecular haematology Non-hodgkin lymphoma

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spelling	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual diseaseAlcoceba, MiguelStewart, James P.García-Alvarez, MaríaDíaz, Luis G.Jiménez, CristinaMedina, AlejandroChillón, M. del CarmenGazdova, JanaBlanco, ÓscarDíaz, Francisco J.Peñarrubia, María J.Fernández, SilviaMontes, CarlosCabero, AlmudenaCaballero, Maria DoloresGarcía-Sanz, RamónGonzález, MarcosGonzález, DavidTamayo, PilarGutiérrez, Norma CarmenGarcía-Sancho, Alejandro MartínSarasquete, María EugeniaLiquid BiopsyMinimal residual diseaseMolecular haematologyNon-hodgkin lymphomaCirculating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.This study was funded by Instituto de Salud Carlos III (ISCIII), PI21/01553, PI21/00109 cofunded by the European Union; Gerencia Regional de Salud de la Junta de Castilla y León: 1652/A/17, 2271/A/20 and 1661/A/17; Asociación Castellano-Leonesa de Hematología y Hemoterapia. Convocatoria 2017 “Enfermedad mínima residual en linfoma difuso de célula grande B en ADN tumoral circulante mediante PCR digital”. Funding by the Spanish Ministry of Economy and Competitiveness CIBERONC-CB16/12/00233 and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010) is also acknowledged. MES was supported by the Instituto de Salud Carlos III (Contrato Miguel Servet tipo II CPII18/00018), C.J. by Contrato Sara Borrell CD19/00030, and MGA and AM by the Spanish Society of Haematology Foundation (FEHH). Fundación GILEAD (GLD18/00063) is also acknowledged.Peer reviewedJohn Wiley & SonsInstituto de Salud Carlos IIIJunta de Castilla y LeónFundación Castellano Leonesa de Hematología y HemoterapiaSociedad Española de Hematología y HemoterapiaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/381200reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1111/bjh.19458https://doi.org/10.1111/bjh.19458Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3812002026-05-22T06:33:51Z
dc.title.none.fl_str_mv	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
title	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
spellingShingle	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease Alcoceba, Miguel Liquid Biopsy Minimal residual disease Molecular haematology Non-hodgkin lymphoma
title_short	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
title_full	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
title_fullStr	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
title_full_unstemmed	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
title_sort	Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease
dc.creator.none.fl_str_mv	Alcoceba, Miguel Stewart, James P. García-Alvarez, María Díaz, Luis G. Jiménez, Cristina Medina, Alejandro Chillón, M. del Carmen Gazdova, Jana Blanco, Óscar Díaz, Francisco J. Peñarrubia, María J. Fernández, Silvia Montes, Carlos Cabero, Almudena Caballero, Maria Dolores García-Sanz, Ramón González, Marcos González, David Tamayo, Pilar Gutiérrez, Norma Carmen García-Sancho, Alejandro Martín Sarasquete, María Eugenia
author	Alcoceba, Miguel
author_facet	Alcoceba, Miguel Stewart, James P. García-Alvarez, María Díaz, Luis G. Jiménez, Cristina Medina, Alejandro Chillón, M. del Carmen Gazdova, Jana Blanco, Óscar Díaz, Francisco J. Peñarrubia, María J. Fernández, Silvia Montes, Carlos Cabero, Almudena Caballero, Maria Dolores García-Sanz, Ramón González, Marcos González, David Tamayo, Pilar Gutiérrez, Norma Carmen García-Sancho, Alejandro Martín Sarasquete, María Eugenia
author_role	author
author2	Stewart, James P. García-Alvarez, María Díaz, Luis G. Jiménez, Cristina Medina, Alejandro Chillón, M. del Carmen Gazdova, Jana Blanco, Óscar Díaz, Francisco J. Peñarrubia, María J. Fernández, Silvia Montes, Carlos Cabero, Almudena Caballero, Maria Dolores García-Sanz, Ramón González, Marcos González, David Tamayo, Pilar Gutiérrez, Norma Carmen García-Sancho, Alejandro Martín Sarasquete, María Eugenia
author2_role	author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Instituto de Salud Carlos III Junta de Castilla y León Fundación Castellano Leonesa de Hematología y Hemoterapia Sociedad Española de Hematología y Hemoterapia Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	Liquid Biopsy Minimal residual disease Molecular haematology Non-hodgkin lymphoma
topic	Liquid Biopsy Minimal residual disease Molecular haematology Non-hodgkin lymphoma
description	Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.
publishDate	2024
dc.date.none.fl_str_mv	2024 2025 2025
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/381200
url	http://hdl.handle.net/10261/381200
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1111/bjh.19458 https://doi.org/10.1111/bjh.19458 Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	John Wiley & Sons
publisher.none.fl_str_mv	John Wiley & Sons
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	DIGITAL.CSIC. Repositorio Institucional del CSIC
collection	DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease

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