P-151: Dietary oleic acid influences the myeloma immune microenvironment and improves clinical outcomes

Introduction: The impact of the microbiome and dietary interventions on cancer patient outcomes has garnered increased interest in recent years. In various cancer types, microbiome modulation has been linked to patient survival, exemplified by prolonged survival in metastatic melanoma patients following a high-fiber diet. Similar trends are observed in multiple myeloma (MM), where a plant-based diet has positively influenced minimal residual disease (MRD) status in patients treated with lenalidomide. However, further research is essential to fully understand the complex relationship between diet and MM. This study aims to provide evidence-based dietary recommendations to improve outcomes for MM patients.

Methods: This study included 66 newly diagnosed MM (NDMM) patients between July 2021 and April 2023. NDMM patients reported their dietary habits (N=64) using standardized Food Frequency Questionnaires (FFQs). The FFQ data were analyzed with DGExpert, version 2.0, software. Serum (N=26) and bone marrow (N=27) samples were collected before therapy initiation and analyzed by targeted metabolomics. Bone marrow samples were analyzed by flow cytometry. All patients received Dara-VTD induction therapy, with responses evaluated after four cycles using IMWG criteria. To functionally validate dietary impacts on myeloma, BALB/c mice were engrafted with MOPC-315.BM myeloma cells. Mice were fed either a control diet or a diet supplemented with oleic acid.

Results: Close correlations were observed between dietary intake and patient characteristics. Notably, high intake of monounsaturated fatty acids, particularly oleic acid (OA), was associated with a lower ISS stage and a higher rate of complete response (CR) to induction therapy in the patient cohort. Patients with OA intake above the median had a CR rate of 36%, compared to 20% in those with intake below the median. In a multivariate model, this effect was independent of age, ISS, cytogenetics, R-ISS, and BMI. Monounsaturated fatty acid intake was also associated with OA concentrations in serum samples, indicating the potential systemic benefits of OA. Additionally, OA intake correlated with a higher abundance of memory CD8+ T cells in the bone marrow. In a preclinical MM mouse model, feeding mice a diet rich in OA before and after tumor implantation prolonged overall survival (OS).

Conclusions: Our clinical data suggest that a diet rich in plant-based unsaturated fatty acids, particularly OA, influences MM biology and the tumor immune microenvironment, positively affecting clinical outcomes. Notably, we supported our observations in human disease by a preclinical in vivo model of MM, demonstrating prolonged OS with a high OA diet.