ASH 2024 | NUTRIVENTION: a high-fiber dietary intervention improves biomarkers in precursor disorders

At the ASH annual meeting, we presented data on the NUTRIVENTION trial. This is a trial of a high-fiber plant-based diet in patients with MGUS and smoldering myeloma. In this study, given some background data, often an elevated BMI increases risk of myeloma and patients with MGUS and smoldering myeloma with an elevated BMI having twice the risk of progression to myeloma than those with normal BMI. Additionally, with epidemiologic studies showing people eating more plant-forward or plant foods have less risk of myeloma, we wanted to look at whether a diet could slow progression. 

The study was designed as a feasibility study, so it was a 20-patient study. What we did see was that there was a sustained BMI reduction of about 7%, which lasted up to a year out. We also looked at adherence, and the adherence to unprocessed plant foods was 20% at baseline. This increased to 92% at the end of 12 weeks of the intervention, and it was still high at 60% at one year as well, suggesting that the changes patients made are sustained beyond the period of the intervention. 

We next looked at how this intervention is affecting other parameters. So we see an improvement in quality of life. We see an improvement in insulin resistance, or lower fasting insulin levels, and increased adiponectin-leptin ratio. We looked at its effects on the microbiome, and we see an improvement in microbiome diversity, the gut microbiome composition with increased butyrate producers as well. Next, we looked at understanding its effects on the immune system, and we see a reduction in C-reactive protein, a marker of inflammation, and a reduction in the neutrophil count, which suggests reduction in inflammation too. We did peripheral blood flow cytometry and bone marrow single-cell RNA sequencing. What we did see in terms of changes in immune subsets was there was an increase in CD14 classical monocytes that are anti-inflammatory and a reduction in CD16 inflammatory classical non-classical monocytes. So we see a shift in the immune system too and this was similar to what we’re seeing in the bone marrow. We looked at cell interactions and we see that the myeloid cells at baseline were interacting mainly with the exhausted CD8 T-cells. At the end of the intervention, they were interacting mainly with CD8 cytotoxic T-cells and natural killer cells suggesting enhanced anti-tumor immunity as well. 

Next, we looked at changes in the myeloma protein trajectory before and after intervention. So we had data for patients in terms of the rate of change of M-spike per month before intervention to on and after intervention. For two patients who are clearly rising M-spikes before intervention, there was a stabilization on intervention and post-intervention suggesting that this may have delayed progression.

 In collaboration with the Matteo Bellone lab in Italy and his postdoc, Laura Cogrossi, we performed mouse models. In these mouse models, these were smoldering myeloma VK-myc mouse models. And we showed in this that when these mice were given either a standard diet or a high-fiber diet and followed for progression to myeloma, we saw that 44% of the mice on the high-fiber diet did not progress to myeloma, whereas all mice on the standard diet progressed to myeloma at the end of the experiment. This confirms the findings of what we’re seeing in patients, and there were very consistent immune and microbiome changes as well. 

Therefore, we think that a high-fiber plant-based diet can help with weight management, insulin resistance, microbiome composition, immune changes, enhanced anti-tumor immunity, and potentially also slow progression for patients. So multiple mechanisms through it. We have the NUTRIVENTION III trial enrolling at Memorial Sloan Kettering. Currently, this is a much larger 150-patient study looking at diet and supplements in patients with these precursor disorders.

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