P-482: Dietary habits correlate with myeloma pathogenesis and treatment outcome in multiple myeloma

Introduction: Dietary interventions in multiple myeloma (MM) have recently gained interest due to the interplay between the gut microbiome and tumor biology. However, the extent to which specific nutrients can modify myeloma pathogenesis through interactions with the microbiome and immune system remains to be elucidated. This study investigated the association between dietary patterns of patients with MM and their disease characteristics and treatment outcomes.

Methods: 62 newly diagnosed MM (NDMM) patients were included in this study between July 2021 and April 2023. NDMM patients reported their dietary habits using a standardized Food Frequency Questionnaire (FFQ). The FFQ data were then analyzed using DGExpert2.0 software. All patients received Dara-VTD induction therapy. Response after four cycles was assessed according to IMWG response criteria. The impact of dietary habits on myeloma pathogenesis was validated using an immunocompetent preclinical model of MM in BALB/c mice. Mice harboring MOPC-315 myeloma grafts were administered both a control diet and a diet supplemented with oleic acid (n=10/group), aiming to replicate the nutritional characteristics observed in NDMM patients.

Results: When examining the intake of specific fatty acids, the consumption of long-chain unsaturated fatty acids showed a significant correlation with decreased tumor burden in patients classified with International Staging System (ISS) Score I compared to those with ISS Score II and III (Oleic acid: p< 0.001, Linoleic acid: p=0.005). In contrast, higher carbohydrate intake, driven by sucrose consumption, was linked to elevated ISS scores (ISS I vs. II/III, Carbohydrates: p=0.007, Sucrose: p< 0.001). In line, a dietary pattern rich in plant-based unsaturated fatty acids and low in sucrose was associated with lower levels of plasma cell infiltration in the bone marrow and reduced paraprotein production. When comparing the dietary intakes of different responder groups, patients who reported lower sucrose consumption and higher intake of unsaturated fatty acids exhibited a higher likelihood of achieving a complete response (CR) (Sucrose: p< 0.001 and Oleic acid: p< 0.001 for CR vs. non-CR). In the preclinical mouse model, a higher intake of oleic acid was found to confer a significant survival advantage (p=0.048).

Conclusions: Our clinical data suggests that a diet rich in plant-based unsaturated fatty acids, particularly oleic acid, and low in sucrose modulates myeloma biology and positively influences therapy outcomes in NDMM patients. These observations were supported by a preclinical in vivo model. Collectively, our study emphasizes the importance of considering dietary interventions as an indispensable adjunct in supporting and optimizing anti-myeloma therapy.