Targeted metabolomic profiling of multiple myeloma: diagnostics and treatment efficacy

Introduction. Multiple myeloma (MM) is a malignant disease of plasma cells characterized by marked heterogeneity of the clinical course and variability in response to treatment. Metabolomic analysis, which reflects the totality of small molecules in biological fluids, opens up new possibilities for the search for diagnostic and prognostic biomarkers.

Aim. To evaluate metabolomic profiles of patients with multiple myeloma (MM) and to identify metabolic markers associated with the efficacy of polychemotherapy.

Materials and methods. The study was conducted from September 2022 to May 2025 at the Department of Hospital Therapy No. 1 of Sechenov University. We performed targeted analysis of plasma metabolites in 29 pre-treatment MM patients and 30 healthy volunteers (controls). Patients were divided into response and no response groups based on the results of therapy with VCD protocol after three courses.

Results and discussion. Significant differences in metabolomic profiles of MM patients compared to controls were found. MM patients showed increased tryptophan catabolism via the kynurenine pathway (~41 % increase in kynurenine/tryptophan ratio, ~80 % decrease in serotonin levels), changes in urea and nitric oxide cycle metabolites (~28 % decrease in arginine, ~5.3-fold increase in asymmetric dimethylarginine), and amino acid imbalances (decrease in serine, aspartate, BCAA) and a significant increase in total acylcarnitines (~1.4-fold higher than control). The baseline metabolic profile also differed between patients with different treatment outcomes: before treatment, patients who subsequently showed a clinical response had lower levels of several acylcarnitines and tryptophan breakdown products (e.g. anthranilic acid), whereas patients without response showed decreased levels of 5-hydroxytryptophan, indole-3-lactic acid and histidine.

Conclusions. Metabolomic analysis revealed characteristic metabolic alterations in MM reflecting activation of immunometabolic pathways (tryptophan kynurenine pathway, arginine metabolism) and impaired energy and amino acid regulation. The results indicate the potential prognostic significance of metabolites: a number of biomarkers (e.g. tryptophan derivatives, acylcarnitines) may be associated with chemotherapy sensitivity. The findings open the prospects for further research on metabolic approaches in MM monitoring and therapy.

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