Ketone bodies and their potential as biomarkers in relapsed/refractory diffuse large B-cell lymphoma

New Findings in DLBCL Research

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. While most patients respond favorably to initial treatment, a significant percentage develop relapsed or refractory (R/R) disease, which limits therapeutic options and worsens prognosis.

A recent study published in the journal Cancers has identified two metabolic biomarkers that may predict the clinical evolution of patients with R/R DLBCL. These are 3-hydroxybutyrate (3OHB) and acetone, compounds known as ketone bodies, whose presence in serum has been directly associated with survival in patients treated with a combination of lenalidomide, rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP).

A Pioneering Study in Lymphoma Metabolomics

The study, conducted as part of the R2-GDP-GOTEL clinical trial, analyzed serum samples from 69 patients using nuclear magnetic resonance (NMR) spectroscopy. The results were significant:

  • Elevated levels of 3OHB above 141 µM were associated with a worse prognosis, particularly in patients with the ABC subtype of lymphoma.
  • Acetone, at concentrations above 40 µM, was also identified as a marker of poor prognosis, present in both DLBCL subtypes but with a higher incidence in the ABC subtype.
  • These biomarkers were independent of the International Prognostic Index (IPI) and the refractory status of the disease, making them valuable complementary tools for risk stratification.
Figure 1. 3-hydroxybutyrate and acetone as prognostic metabolites in the Cox univariate analysis (A,B) and multivariate regression models (C–F) for progression-free survival (PFS) (A,C,E) and overall survival (OS) (B,D,F).

Development of Predictive Models

To facilitate the clinical application of these findings, the researchers designed predictive models, known as nomograms, that integrate 3OHB and acetone levels with other relevant clinical factors. These models demonstrated high predictive accuracy:

  • 3OHB had an area under the curve (AUC) of 0.856 for progression-free survival at 6 months.
  • For overall survival at 12 months, the AUC of 3OHB was 0.844.

These results suggest that incorporating these biomarkers into patient evaluations could contribute to more personalized and precise therapeutic decision-making.

Relevance of the Findings in Oncology

Cancer metabolism is an evolving field of research. It has been demonstrated that some tumor cells primarily rely on glycolysis for energy (Warburg Effect), while others utilize fatty acid oxidation and ketone bodies.

This study suggests that certain lymphomas, particularly those of the ABC subtype, may use ketone bodies as an energy source, which is associated with a poorer treatment response. The detection of elevated 3OHB and acetone levels in serum could indicate metabolic reprogramming of the tumor, allowing for the identification of patients with a worse prognosis and the adjustment of their therapeutic strategies accordingly.

While this study focused on patients treated with the R2-GDP regimen, further research is needed to:

  • Validate these biomarkers in previously untreated DLBCL patients.
  • Explore their relationship with new therapies, such as CAR-T cell treatments and bispecific antibodies.
  • Develop clinical tools based on metabolomics to improve treatment personalization.

This advancement represents a significant step toward precision oncology, where studying tumor metabolism could be key to predicting lymphoma progression and improving patient survival.

If you are a researcher and want to learn how NMR-based metabolomics can support your studies, do not hesitate to contact us! We would be delighted to explore new opportunities in biomarker analysis together and contribute to improving health through research.

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