High-Fiber NUTRIVENTION Study for Delaying Progression of Myeloma | Urvi Shah, MD | #ASH24

Hi, I'm Urvi Shah, hematologist and oncologist at Memorial Sloan-Kettering Cancer Center in New York City. Very excited to be at the ASH annual meeting to present the updates on our nutrivention trial. The nutrivention trial was a pilot study looking at a high fiber, plant based diet in patients with precursor plasma cell disorders, that’s MGUS and smoldering myeloma, and, to look at if this could delay progression to myeloma.

The study was a pilot study, so it was a feasibility design looking at if patients could actually adhere to this if this helped with weight loss. The reason we did this study was because we know that obesity increases the risk of progression from MGUS to myeloma, and also that people who eat more plant and high fiber foods tend to have lower risk of myeloma.

So we wanted to see if we could help patients make these changes and then see if that could affect outcomes. In the study, we did see that, we gave patients 12 weeks of a high fiber plant based diet, 24 weeks of nutrition coaching, and, patients could eat to satiety with no calorie restriction. And they were followed for a year on the study.

Patients had a reduction in insulin levels. Fasting insulin levels. They also had an improvement in the microbiome composition and diversity, as well as, immune system, where there was a reduction in inflammation, in immune subsets shifted to an anti inflammatory subsets, and also more interaction with the cytotoxic CD8 cells or the natural killer cells or enhanced anti-tumor immunity.

What we also saw is that patients had improved quality of life. The primary endpoint of their study, which was adherence and BMI reduction, we saw a BMI reduction of about 7% at 12 weeks. That was sustained a year out despite no calorie restriction. We also saw adherence that went from 20% of their calories being unprocessed plant foods to over 90 to 90% of calories.

And this sustained even at one year out to close to 60%, suggesting that once the patients made the changes and saw the benefits, they were able to continue it long term. Next we looked at changes in the M spike trajectory. And what we did see was that, the rate of change of progression before and after intervention for two patients was clearly rising before intervention and slowed down on intervention, suggesting that there may have been a delay in progression.

In collaboration with Matteo Bellone and his laboratory in Italy, and his postdoc, Laura Cogrossi, we did mouse modeling. And what we did show in that this is a Vk*MYC smoldering myeloma mouse model. And in this mouse model, the mice were either fed a standard diet or a high fiber diet. The mice that got the standard diet, all of them progressed by the end of experiment to myeloma.

The mice that got this high fiber diet, 44% had not progressed by the end of the experiment, suggesting the benefits of a high fiber, plant based diet, potentially for risk reduction. We also looked at, so the different mechanisms we've talked about is around BMI, insulin resistance, microbiome, immune system and short chain fatty acids that could affect outcomes.

So with that, we have the nutrivention-3 trial enrolling at Memorial Sloan Kettering and also at Emory in Atlanta. This study requires patients to come to one of these sites for five times spread over a year. And, they can otherwise be anywhere in the country as long as they're willing to travel. Now it's about 50% enrolled, and we're looking for other patients with mGUS and smoldering that might be interested in this.

So the nutrivention-3 trial is an extension of the nutrivention. So the intervention is very similar. But we are also looking at supplements like omega three algae based and curcumin to see if these have effects on the microbiome and immune system too. So patients get randomized to three arms, either diet supplements or placebo supplements.

And the two supplement arms, the placebo and supplement are double blinded, meaning that the patient wouldn't know and the doctor wouldn't know what arm they are on. But at the at the end of that intervention, we do unblind and let the patient know what they were on. All patients on the study do get the diet. So the ones that do get the supplements or placebo supplements get the diet just three months later.

And so patients are followed for a year, to two years on the study, but they need to come to MSK about five times spread over a year. So as long as their or, Emory as well. So as long as they're willing to travel for those. We've had patients from many different states, enroll as well.

So, I think in terms of when we talk about a high fiber plant based diet, we're thinking about, and for gut microbiome health, a lot of data shows that, one study specifically looked at the number of plant foods per week individuals ate and correlated it with microbiome diversity and composition, and showed that those who get more than 30 types of plant foods.

We're talking about variety. Not the same foods 30 times, but 30 different plant foods per week have better microbiome health compared to those who eat less than ten plant foods per week. We also know that fermented foods such as kimchi, sauerkraut, yogurt, miso, natto, all of these different, fermented foods are actually very beneficial to gut health as well.

And in healthy individuals have shown to lower inflammation and improve gut microbiome diversity as well. Fiber only comes from plant foods and unprocessed plant foods mainly. So often, the US population doesn't get enough fiber. So that's something, you know, that could be something you could think about in your diet. Maybe adding a couple of beans a day will give you 15g of protein and 15g of fiber.