Ketone Bodies Are Potential Prognostic Biomarkers in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results from the R2-GDP-GOTEL Trial

<b>Background:</b> Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for high-dose chemotherapy have limited treatment options and poor life expectancy. The purpose of this study is to identify a serum metabolomic profile that may be predictive of outcome in patients with R/R-DLBCL. <b>Methods:</b> This study included 69 R/R DLBCL patients from the R2-GDP-GOTEL trial (EudraCT 2014-001620-299). Serum samples were collected at baseline, and the mean length of follow-up was 41 months. Serum metabolites were analyzed by nuclear magnetic resonance (NMR). Metabolites were correlated with treatment response, progression-free survival (PFS), and overall survival (OS). <b>Results:</b> Serum levels of 3-hydroxybutyrate (3OHB) and acetone were significantly (<i>p</i> < 0.001) associated with PFS (3OHB: hazard ratio [HR] 7.7, 95% confidence interval [CI] 2.5-24.1; acetone: HR 9.32, 95% CI 2.75-31.6) and OS (3OHB: HR 9.32, 95% CI 2.75-31.6; acetone: HR 1.92, 95% CI 1.36-2.69). Serum values of 141 µM for 3OHB and 40 µM for acetone were the optimal cutoffs associated with the survival outcomes. Elevated 3OHB levels (>141 μM) were specific to the ABC subtype of DLBCL, while acetone levels were elevated in both types of DLCBL but more pronounced in ABC cases. In a multivariate survival analysis, including the International Prognostic Index (IPI) score and refractoriness status (R/R), 3OHB and acetone remained significant. To aid oncologists employing the R2-GDP regime, we constructed PFS and OS nomograms for R/R-DLBCL risk stratification, incorporating 3OHB levels or acetone levels, IPI score, and refractoriness status. The nomogram with 3OHB and refractoriness status showed a time-dependent AUC of 0.86 for 6-month PFS and 0.84 for 12-month OS. These nomograms provide a comprehensive tool for individualized risk assessment and treatment optimization. <b>Conclusions:</b> The ketone bodies 3OHB and acetone are potential prognostic biomarkers of poor outcome in R/R DLBCL patients treated with the R2-GDP regimen, independently of IPI score and chemorefractoriness status.

Authors

Institutions

Publication Details

Journal
Cancers
Published
2025-02-05
DOI
https://doi.org/10.3390/cancers17030532
Citations
3
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
2.81

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Ketone Bodies Are Potential Prognostic Biomarkers in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results from the R2-GDP-GOTEL Trial

Núria Amigó, Esteban Nogales, Eduardo Ríos, Fátima de la Cruz‐Vicente et al.
3 citations
Cancers
Cancer, Hypoxia, and Metabolism
2.81
article

Ketone Bodies Are Potential Prognostic Biomarkers in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results from the R2-GDP-GOTEL Trial

Núria Amigó, Esteban Nogales, Eduardo Ríos, Fátima de la Cruz‐Vicente, Luis de la Cruz‐Merino, María Guirado-Risueño, José Gómez‐Codina, Jorge Labrador, Raquel Cumeras, Josep Gumà, Natalia Palazón‐Carrión, Francisca Martínez-Madueño, Víctor Sánchez‐Margalet, Carlos Jiménez‐Cortegana, Alejandro Martı́n, Margarita Sánchez‐Beato, Joan R. Badia, Delvys Rodríguez‐Abreu, Antonio Rueda‐Domínguez, Fernando Carnicero-González, Antonio Salar-Silvestre, Sara Fernández‐Castillejo, Laura Gálvez, Mariano Provencio, Guillermo Rodríguez‐García, Natividad Martínez-Banaclocha
article en
3 citations

Abstract

<b>Background:</b> Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for high-dose chemotherapy have limited treatment options and poor life expectancy. The purpose of this study is to identify a serum metabolomic profile that may be predictive of outcome in patients with R/R-DLBCL. <b>Methods:</b> This study included 69 R/R DLBCL patients from the R2-GDP-GOTEL trial (EudraCT 2014-001620-299). Serum samples were collected at baseline, and the mean length of follow-up was 41 months. Serum metabolites were analyzed by nuclear magnetic resonance (NMR). Metabolites were correlated with treatment response, progression-free survival (PFS), and overall survival (OS). <b>Results:</b> Serum levels of 3-hydroxybutyrate (3OHB) and acetone were significantly (<i>p</i> < 0.001) associated with PFS (3OHB: hazard ratio [HR] 7.7, 95% confidence interval [CI] 2.5-24.1; acetone: HR 9.32, 95% CI 2.75-31.6) and OS (3OHB: HR 9.32, 95% CI 2.75-31.6; acetone: HR 1.92, 95% CI 1.36-2.69). Serum values of 141 µM for 3OHB and 40 µM for acetone were the optimal cutoffs associated with the survival outcomes. Elevated 3OHB levels (>141 μM) were specific to the ABC subtype of DLBCL, while acetone levels were elevated in both types of DLCBL but more pronounced in ABC cases. In a multivariate survival analysis, including the International Prognostic Index (IPI) score and refractoriness status (R/R), 3OHB and acetone remained significant. To aid oncologists employing the R2-GDP regime, we constructed PFS and OS nomograms for R/R-DLBCL risk stratification, incorporating 3OHB levels or acetone levels, IPI score, and refractoriness status. The nomogram with 3OHB and refractoriness status showed a time-dependent AUC of 0.86 for 6-month PFS and 0.84 for 12-month OS. These nomograms provide a comprehensive tool for individualized risk assessment and treatment optimization. <b>Conclusions:</b> The ketone bodies 3OHB and acetone are potential prognostic biomarkers of poor outcome in R/R DLBCL patients treated with the R2-GDP regimen, independently of IPI score and chemorefractoriness status.

CancersVol. 17(3)
Universidad de Salamanca (ES), Hospital Universitario Insular de Gran Canaria (ES), Instituto de Salud Carlos III (ES), Hospital Universitari i Politècnic La Fe (ES), Hospital Universitario Virgen Macarena (ES), Institut de Recerca Biomèdica Catalunya Sud (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Hospital San Pedro de Alcántara (ES), Hospital Universitario de Burgos (ES), Hospital General Universitario de Elche (ES), Hospital Del Mar (ES), Instituto de Biomedicina de Sevilla (ES), Instituto de Investigación Biomédica de Salamanca (ES), Hospital General Universitario de Alicante Doctor Balmis (ES), Hospital Universitario de Valme (ES), Hospital Universitari Sant Joan de Reus (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Clínico Universitario Virgen de la Victoria (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) (ES), Universitat Rovira i Virgili (ES)
Centres de Recerca de Catalunya, Generalitat de Catalunya, Spanish Clinical Research Network
Decent work and economic growth, No poverty
Openalex Percentile: Top 11%
Cancer, Hypoxia, and Metabolism
2.81
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.