What is within a patient's control to slow or stop progression from MGUS or smoldering myeloma to active myeloma? And which supplements have any impact at all on our precursor condition or myeloma health? 

Urvi Shah, MD of Memorial Sloan Kettering Cancer Center is running a series of studies called the NUTRIVENTION series to aggregate sufficient data to answer these critical questions. The first NUTRIVENTION study was an extensive, multi-month study that showed that a whole foods plant-based diet could actually slow disease progression. 

Because Dr. Shah knows that the microbiome (or your gut health) has an impact on inflammation (which influences disease progression), she is now running the second study called NUTRIVENTION-2 study to identify the impact a whole foods plant based diet or supplements have on the microbiome. HealthTree is supporting Dr. Shah's study with study support as well as direct funding.

The study invites MGUS or smoldering myeloma patients (who are not on active treatment) to join the study for a 2-week intervention with one group implementing a 2-week whole foods plant-based diet, or the other three groups receiving one of three different types of supplements. Four in-home stool samples will be collected during the study to identify if the diet or an individual supplement improves microbiome health. Participation is virtual and no travel is necessary. 

We invite you to join this study if you are an MGUS or smoldering myeloma patient today! 

Join the NUTRIVENTION-2 Study

In this show, Dr. Shah shares her findings about the impact on diet, describes the NUTRIVENTION-2 study for MGUS and SMM patients, shares an upcoming study for newly diagnosed myeloma patients and also reveals her 5 top tips to more easily move towards a whole foods plant based diet. 

 

Jenny: Welcome to today's episode of the Health Tree podcast for Multiple Myeloma, a show that connects patients with myeloma researchers. I'm your host, Jenny Ahlstrom.

Before we get started with today's show, I'd like to give everyone a heads up for March, Myeloma Awareness Month (as it began yesterday!)

As the leader in digital health advocacy, Health Tree will be making five major technology announcements - one each Monday during the month of March. Please join us at 11 a.m. Pacific, noon mountain, 1 p.m. Central and 2 p.m. Eastern for a short live stream every Monday as we announce ways to help you better navigate your myeloma care using Health Tree technology.

It's very exciting and we can't wait to show you how Health Tree is leading the way to advance care and research. In anticipation of these announcements, we invite you to join the HealthTree CureHub registry because you will find many of these new technologies will be found inside of the Registry. You can create or update your account by going to the menu bar and clicking on CureHub.

The HealthTree Care Hub Registry is a way for 100 % of patients to support academic center research, which we are always supportive of, as you will hear in this show.

So now onto our show today. Patients are always asking what they can do to slow the progression of their disease. And today we will talk about an empowering way of living that could impact both the progression from a precursor condition to active myeloma or strategy that might even help keep you in myeloma remission longer for the relapsed patient.

We will talk about how HealthTree is helping advance this academic research with its tools and services. So we have with us today Dr. Urvi Shah. Dr. Shah, welcome to the program.

Dr, Urvi Shah: Thank you so much, Jenny, for having me. I look forward to chatting with you over the next hour.

Jenny: That's great. Thank you for joining. And let me give you an introduction before we get started. Dr. Urvi Shah is an Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center and Assistant Professor of Medicine at Weill Cornell Medicine. She completed a residency in internal medicine at Tufts Medical Center, fellowships in hematology and oncology at Montefiori Medical Center, and in cancer immunotherapy at MSKCC and the Parker Institute for Cancer Immunotherapy in New York.

She's board certified in internal medicine, hematology, and medical oncology. She's also received a Master of Science degree in clinical and translational cancer research in 2024. Now her own personal experience being treated for Hodgkin lymphoma during her oncology fellowship in 2016 led to her interest in studying the role of different modifiable risk factors like diet, metabolism, and the microbiome in cancer prevention, treatment, and survivorship.

She opened the first pilot nutritional trial in plasma cell disorders to date and a series of trials called NUTRIVENTION. And the first in 2021 that completed enrollment, she has three other NUTRIVENTION and immune therapy investigator-initiated trials currently enrolling. Dr. Shah has been supported by Career Development Awards from the National Cancer Institute the Paul Kalabreski K-12 International Monoloma Society and American Society of Hematology Scholar Awards as well as HealthTree Foundation.

She's also received the ASH CRTI Award, the ECOG Akron Young Investigator Translational Research Award, the Henry Moses Prize, the Celgene Future Leaders in Hematology Award, the NCI Early Investigator Advancement Program, Clinical Cancer Research Early Cancer Award, and the ASH David Goldberg CRTI Award.

Dr. Shah has published first author papers in prominent journals like Blood and Clinical Cancer Research, among others, and has been an invited speaker and session chair nationally and internationally.

It’s so wonderful, and I think you're really one of the leaders in this entire space. So it's very exciting to watch your research grow and see just all the amazing things that you're doing. It's so fun to watch.

Dr. Urvi Shah: Thank you so much Jenny and I still remember the beginning when I started and we started partnered with HealthTree to spread awareness and start discussing this. So I'm incredibly grateful to your support and HealthTree Foundation for making this research important and grow.

Jenny: It's so fascinating. It's one thing that patients can do. So let's just have you answer the question. Why does nutrition matter for precursor condition and myeloma patients?

Dr. Urvi Shah: So I think when patients get diagnosed with a cancer, whether it's myeloma or a pre-cancer state, the first thing that comes to mind is what caused it and is there something I can do to delay its progression or improve my outcomes?

And we're all looking for something where it may be a lower risk intervention, not like the chemotherapy, but we know that that's effective and we need to think about that, but maybe can we do something in conjunction with it?

And so the challenge for oncologists and for patients is that there's not enough research that is done at the same level or evidence as we have for drug studies. And so then it becomes hard for the doctor to recommend something and hard for the patient to feel motivated to follow it because they feel like, I really doing the right thing? Is it going to help or not?

So part of my motivation is to try to bring this evidence, the same kind of rigor for dietary trials as we do for drug studies and help patients have that evidence where they can now think about really if they want to make these changes, at least they have the information. And when we think about why it could be helpful, I think there are multiple reasons. One is could it slow progression or delay progression or increase long-term survival if it's depending on the situation a patient is in?

Or could it improve quality of life? Or could it be that it may not affect the cancer directly, but it could affect comorbidities (other health issues) that affect cancer outcomes or lead to patients living shorter lives such as diabetes, obesity, cardiovascular disease? So if we can help patients live better, we can help them actually respond better to treatment or at least tolerate treatments better too.

Jenny: Amazing. There are a lot of impacts. You mentioned diabetes, but that affects kidney function and that's a big deal in myeloma care. So it's all connected. It's not just myeloma. Well, I know we'll be talking a lot about something called the microbiome today because that is impacted by diet. Do you want to give us a primer on what the microbiome is? And then how does the microbiome affect your body or just how does diet affect your body?

Dr. Urvi Shah: So true, yes.

Sure. So when we think about how diet affects our body, I think it's through multiple mechanisms and microbiome is one of them. And if you think about the mechanisms, it's diet affecting insulin resistance and that affecting inflammation or the immune system, but also obesity or excess adiposity (fat) that leads to inflammation.

Diet or fiber-rich foods directly through like the minerals, vitamins, flavonoids in them, and the fiber lead to direct outcomes where they affect the immune system. And then thirdly, when we think about diet affecting the microbiome, which is basically the microorganisms that live inside of us and around us, diet most likely is going to affect the gut microbiome the most likely compared to the skin microbiome or other areas.

It's important because we are more microbiome than humans. So if we think about the number of cells, we are probably 30 trillion human cells, but 38 trillion microbiome. And if we think about like you're born with certain DNA, you can't really change that. But the good thing about the microbiome is it changes on a day-to-day basis based on where we are, what we eat, things like that.

In one way, it's empowering to know that we can actually change the DNA of the microbiome or change the microbiome a little bit based on what we actually do. And that may affect outcomes because the microbiome directly affects the immune system through short chain fatty acids or other molecules that the microbiome produce. And that could lead to reductions in inflammation. And we know that the immune system is very tightly linked to cancer.

And you know that from immune therapies now in myeloma and all cancers where they're so effective, that just tells us that the immune system is very tightly linked in how cancer can be controlled.

So just going to show that there are multiple mechanisms around which diet can affect cancer directly through molecules, through the microbiome and molecules that it makes or through insulin resistance and adiposity, those would I would think be three major ways to think about it.

Jenny: And I think I've heard other people say that everyone has these cancer cells potentially floating around in our body. And usually our body is doing a very good job of killing the cells. And in some instances, maybe one or multiple things happen to help, trigger, develop or progress (cancer) or whatnot. But this is one of the things that we might have control over.

Dr. Urvi Shah: Yes, I completely agree. It's a balance between the genetics or the cancer cell of the cancer versus the immune system. And when the cancer is active, the immune system is overwhelmed and the cancer has taken over the immune system. But when we strengthen the immune system, we may be able to help control the tumor. So it's really a balance between the two.

Of course, it may not work in every situation because sometimes we need the reduction of the chemotherapy to bring the burden of disease down before the immune system can get activated again because it may be overwhelmed by the cancer. And diet is a lower risk or intervention compared to, and a lower effect intervention compared to maybe drugs for the most part, but that doesn't mean it's not effective.

Jenny: And I know when it comes to diet, I think the whole nation or world might be confused about what to eat because depending on what you look at, it's so confusing. It's like the high protein diet, the low carb diet, the keto diet. But most of your research is talking about this whole foods plant-based diet. So can you explain what that means?

Dr. Urvi Shah: Sure. So when you think about whole foods, basically means you're thinking about unprocessed foods or eating more whole fruits and vegetables instead of like a processed juice.

Then when plant-based, meaning that the majority of calories are coming from plant-rich foods. And the reason for that is because the majority, only unprocessed plant foods really have fiber.

So when you want to eat a fiber-rich diet, you need a plant predominant or a plant-based diet, which is unprocessed. So you could call it a high fiber plant-based or a whole food plant-based, but the majority of calories coming from that. And I like to say about 80 to 90% of calories, but also to remember that plant foods are very low in calorie density. So sometimes people may think that they are getting 80 to 90% of their calories because they're looking at it by what they see 80 to 90%, but sometimes that piece of meat may be most of your calories.

So it may not really be 80 to 90%, even though in volume you're seeing it looks like it is less. When you look at the calorie count, it's higher and the percentage would switch. So it's important to think about it more from the percentage of calories.

Really predominantly plant foods are associated with improved outcomes in cardiovascular disease or diabetes, weight, all of these things that we know. And we wanted to understand what happens for patients with precursor plasma cell disorders like monoclonal gammopathy or smoldering myeloma to see if those can also help in those conditions as well.

Jenny: Well, let's just dive into that. A lot of this is related, like I said in the introduction, with your own personal experience of having lymphoma. So do you want to share how this became part of your story and why you decided to do some of this research?

Dr. Urvi Shah: Sure. So I went through medical school residency fellowship in the beginning, pretty much treating patients the way we've been taught in the traditional way of thinking about the drugs. And if a patient had diabetes, I would talk about insulin and metformin and all the options. if they had cardiovascular disease, talk about the drugs for hypertension and heart rate control and things like that.

When I myself in 2016 at the end of my first year of fellowship got diagnosed with Hodgkin's lymphoma and I went through four months of chemotherapy and this is the old school chemotherapy, not like what we see in myeloma so much so it has really got those side effects.

I did find that I had friends and family members telling me maybe you should try this certain fruit that has anti-cancer properties or have this supplement. And I just realized at that point that despite going through all this training, I don't really know whether there's a lot of data or what the data is.

After I finished my treatment, just as a hobby, I would read some of these books around it and even the literature to try to understand. And then I realized that there's a lot of evidence, whether it's for cardiovascular disease, diabetes, and maybe not as much in cancer, but there is evidence around how people have reversed some of these diseases or at least put them in remission or control with just making dietary changes alone.

And that opened up a whole area which I had not thought about as something that we could study or think about in more detail. And so I was still a fellow at that time. And even though I was interested in this, I didn't really know where to start or how, because I'm transitioning between institutions.

And so I decided maybe eventually that's something I'd like to think about more, but I didn't know whether it would lead to a full career in it or something like that.

Then when I started at Memorial Sloan Kettering in 2019 as, 2018 as a fellow and then 2019 as faculty, I at that time was also mainly just doing research on immune therapies and one project with Dr. Alex Lesokhin was looking at the microbiome and I said, maybe can we also look at diet? And then that project was in patients on lenalidomide maintenance. And that we published in Clinical Cancer Research showing that patients who are more likely to be sustained MRD negative actually have better gut microbiome health and diets that are healthier too, suggesting like there is an association between a healthier plant proteins and sustained MRD negativity through the gut microbiome features.

That led to, and while that research was going on and I had become faculty, had discussed with my chief at that time and said, maybe could I open a pilot study to see maybe an MGUS or smoldering myeloma and see how diet plays a role.

And I really thought that that would be a side project and one study I would do and I would continue to do the immune therapy research I was doing. But really my passion was in that or I found that interesting because I felt like that's where I could make a difference. It's something that nobody's really looking at and patients really want. that fast forward that led to the next study.

And I think when we were developing that study, Cindy connected me with you, Jenny, and then we started talking about doing a study with HealthTree. So we have the NUTRIVENTION-2 study that opened some time later and that study is ongoing and we should talk more about it.

But I think that that's a really great opportunity for patients anywhere in the country to be able to participate. And then since then we have three, four more studies. So in total we have five interventional dietary studies, either ongoing or to begin soon.

Jenny: That's awesome. Well, we are going to talk about one of those studies today in depth and probably talk about one at the end. Do you want to share just about the whole foods, plants based diet in precursor condition patients specifically what you've learned so far?

Dr. Urvi Shah: Yes, so the NUTRIVENTION Pilot Study is completed. We presented the data at the American Society of Hematology meeting and hopefully by sometime this year we'll be able to publish the findings. But that study was looking at a high fiber or a whole food plant-based diet in patients with MGUS and smoldering myeloma who had an elevated body mass index over 25.

We did this as a pilot, so was only 20 patients. But what we did is very detailed in-depth analysis of their immune system, the insulin resistance, the weight, the diet, all of these things, quality of life. And so we could really understand how the dietary intervention could affect these outcomes. And what we saw was that we gave patients three months of meals and six months of coaching for dietary nutritional coaching and followed them for a year.

We saw that patients actually were able to improve their dietary adherence to unprocessed plant foods, quite significantly going from about 20% up to 90% while we were on the intervention. And even a year later, they are at 60%. So way better than where they started. Patients lost about 7% weight because we were looking at aiming for some weight loss. And this was despite eating to satiety, so no calorie restriction because fiber rich foods lead to some satiation and eating less calories.

And then we also looked at quality of life, so global health status. We saw that improve as well. We asked patients if they found this difficult to do. And surprisingly, out of the 15 responses we got, nobody said it was difficult.

And I think that is encouraging for other patients also to see, like once patients actually commit to it and make the changes, I think most patients are able to continue at least some of it for the long term. We saw improvements in many symptoms like GI symptoms, confidence, sleep, anxiety. A patient came off antidepressants, another one came off insulin.

Another patient was able to stop Plequenil. So we've had patients be able to save prescription money to an average of $65 a month. Then, yes, and we had another patient stop potassium supplements because they didn't need that anymore. Then we looked at things like more in-depth correlative, so things like insulin resistance.

Jenny: That's amazing.

Dr. Urvi Shah:  - Despite them eating the same amount of carbs. So this was not a carb restricted diet. It was just switching from refined to complex carbs. And a lot of plant foods have complex carbs because they're fiber rich. We actually saw insulin levels drop adiponectin leptin levels increase and higher ratio is a good thing. Then we looked at the microbiome.

And we talked a bit about the microbiome, but when you think about the microbiome, a more diverse microbiome is a healthier microbiome usually, but also the kind of bacteria are also important, not just the diversity. So the kind of bacteria we want are the healthier butyrate producers or bacteria that make these short-chain fatty acids. We saw both the diversity increase and the butyrate producers increase.

And this was surprisingly sustained for the diversity was sustained even a year out. So I think it's because the patients may, we gave them food only for three months and coaching for six months, but even at the time point of one year, when we looked at the microbiome changes, it was still more diverse than their baseline. And I think this is because they learned some key principles and foundations of healthy eating. And they were, even if a patient didn't continue at 100%,

Jenny: Wow.

Dr. Urvi Shah: Like I said, most of them were doing it 60%. They were still doing some of these things. And it's encouraging to see that even if somebody didn't do it 100%, they're still seeing the benefits long term because they're continuing to make these changes. And then next, we looked at the immune system. So remember, I told you all of these things can affect the immune system. So seven out of our 20 patients had an elevated C-reactive protein. So that's a marker of inflammation.

We saw that this marker dropped by half on average for the patients by the end of the study. So for all the patients, it dropped by 50%. The neutrophil count, which is also a marker of inflammation because it's a white cell, actually went down to at a one month mark. So it was significantly lower compared to baseline. But I think that just shows that there's less circulating need for the neutrophils because there's less inflammation.

But when we looked inside the bone marrow, we didn't see less of the precursor or the cells that make neutrophils, the granulocytes. They were actually increased. So what we think is there's more immune potential, but it's just not circulating because it's not needed to circulate and find the inflammation. And then we also looked at changes in interactions between cells in the bone marrow and how the bone marrow and immune subsets change. We saw that like inflammatory monocytes, which are called non-classical monocytes, they reduced. And the classical monocytes or anti-inflammatory monocytes increased. And we saw that there's an interaction. So when we think about different white blood cells to have anti-cancer effects, they do interact with each other. So we looked at this interaction. And we looked at the interaction between the myeloid cells, so things like monocytes, with the T cells, like CD8 T cells and natural killer cells.

And we saw that in the beginning of the study, these myeloid cells were interacting with the exhausted CD8 cells. And then one year later in the bone marrow, these myeloid cells were now interacting with the cytotoxic CD8 cells, suggesting a switch in the anti-tumor immunity, meaning that now there's less exhaustion but more interaction with the anti-tumor or the cytotoxic or the killer cells.

Then lastly, of course, the question is about the M-spike trajectory. This study enrolled patients which were very heterogeneous. So there were some patients who were newly diagnosed, some who had the disease for a long time.

Some patients with really tiny M-spikes, so it could be like 0.2 or 0.3, and some who had much higher M-spikes because we had MGUS and smoldering myeloma. So that makes it challenging to look at all patients for trajectory changes. But amongst the patients that we have the data, it looks like most of them maintained stable disease.

And we had two patients who were very clearly, because we had enough data before they went on the study where their M-spike was rising over many years, like they were diagnosed five years back, and you could see that M-spike was going up over time. And they stabilized on the study. So it looks like if their trajectory would have been progression faster compared to what happened on the study.

Now, of course, this is two patients, and we need to explore this in bigger studies and other findings. And this is also over time, looking at 20 months after the, for 20 months from start of intervention to 20 months before intervention. But it does suggest that when you improve the immune system with all of these different mechanisms, you might be able to have that effect of the tumor versus immune system tip in a way that may slow progression.

I don't know that it would work for every patient and all disease because if you have very aggressive disease or genetic changes, which are really much more the potent driver of the disease versus the immune system, then maybe dietary changes may not work in that situation. But we have not studied it enough and in a large enough population to understand who does it work in really and who it doesn't. And I think that's the things we need to tease out and understand better.

And I think that this in-depth study gives us an understanding of why it's important to study it beyond. And I think the NUTRIVENTION-2 study gives us that ability. And one of the good things about many things, but one thing is that the NUTRIVENTION-2 study, there is really no data out there for a large population set of microbiome analysis in small ring myeloma or MGUS. We don't really have that kind of data.

Join the NUTRIVENTION-2 Study

With the NUTRIVENTION-2, because we're going to be enrolling about 100 smoldering myeloma or MGUS, we are expanding to MGUS patients as well. I think having different stool samples at varying time points, being able to correlate that with clinical outcomes and understand what's the difference between disease in a small ring myeloma microbiome compared to healthy controls. So we're going to have the optional opportunity for family members or other people to contribute microbiome to so we can compare and understand the effects as well.

Jenny: That's fascinating. So you did this amazing, longer, more in-depth study, and now you have all sorts of research questions. And now I'm very curious about my C-reactive protein and my neutrophil count. So I'm going to go look at my labs after we finish this.

But let's dive into the NUTRIVENTION-2 study. First of all, what are you hoping to learn from this study? And then can you share a little bit about the the structure of the study, the different treatment arms in the study.

Dr. Urvi Shah: Sure. So this study, we designed it specifically in trying to keep it very simple in a way that's decentralized so patients do not need to come to MSK because the challenge with our other studies, our patients need to travel and not all patients are able to or want to travel far to come for a study. So the advantage of the HealthTree study is that you can be anywhere in the United States and take part in the study as long as you have smoldering myeloma and now expanding to MGUS too.

The other advantage is that we actually ship the intervention to you. So you again, you don't really need to go anywhere. For is intervention, we're looking at short interventions for different groups. So we're looking at diet, we're looking at probiotics, we're looking at algae-based omega-3, and we're looking at curcumin.

And the reason we decided to look at these is because these are common supplements that patients with smoldering myeloma and MGUS take, but nobody really knows their effect on the microbiome of MGUS or smoldering myeloma patients and how this can affect outcomes in the long term.

But we know that microbiome changes happen relatively quickly in short periods. So we felt like we could design it with a short intervention of like two weeks long, but collect stool samples at weekly intervals for four weeks. So we can fully get a picture of what happens over time and also be able to just understand the microbiome overall for patients with smoldering myeloma and MGUS.

And this way we can also see how does diet versus supplements affect the microbiome in different ways. So what if somebody didn't want to change their diet? Is the supplement doing something similar to the diet or are there things that the diet does that's different from the supplements?

So I think that because it's a low risk, easy study that can be done from home, it also helps the community of myeloma patients and plasma cell disorder patients and researchers really understand what's going on in the microbiome of smoldering myeloma and MGUS.

So if you have one of those disorders and you're open to participating, it's a short two month study where you have to fill out some surveys online.

And then we ship you stool kits and you ship it back to us. We provide you with return labels for shipping and we also provide the intervention ship to your home. So in those ways, we're trying to make it as easy as possible on the patient.

And we would just need the record shared through HealthTree and you sign onto the consent through HealthTree too. So if you're interested, I would recommend reaching out to HealthTree Foundation and signing up through the survey or the form for the consent online.

Jenny: When we do partnerships like this with investigators like you, we will put the study inside of the platform. So if somebody wants to join, they can just go in there, click sign the consent, and then they start through the process.

So just to recap, so you have four different groups, and one group is a plant-based diet group where you're providing the food, and then the other three groups are just different supplements. So you don't change your diet, you just do the supplements - curcumin…

Dr. Urvi Shah: And the omega-3 and the probiotic.

And also add, it's a randomized design. So patients don't decide which group they go on. It's a 25% chance you get any of those four groups. And once you sign up and you're eligible, we would do a computer-based randomization, tell you which group you are on, and then provide you with the intervention.

Jenny: And it makes so much sense because you know, I've heard of curcumin forever in multiple myeloma and people say you should take this or that supplement. We really don't get to these answers unless you join an actual study like this that is so easy to join. And you said two months, but it's really, you're just doing the intervention for several weeks, right? Two weeks. So it's not like you're making this massive commitment - so it's an easy study to join. It can be joined virtually.

Dr. Urvi Shah: Two weeks.

Jenny: You have a two week intervention, so no need to travel. The food and supplements are provided for free. And then you said you have a series of surveys. Do you want to share a little bit more about that?

Dr. Urvi Shah: Sure, so we going to have patients fill out a dietary questionnaire and also a quality of life questionnaire at certain time intervals. And so I think with that, you may have like online on your computer at home, you can fill these surveys out, but there will be certain time periods. And the patients will also meet with the dietitian. We have about four time points every week or so that you meet with a dietitian to go over what you've eaten so we can just basically record that and understand and correlate that with the microbiome.

Because like I said, diet is one of the biggest drivers of microbiome. And we just want to understand and correlate that too, along with looking at it with smoldering myeloma.

Jenny: And then what are you looking at in the microbiome? Like how diverse is the microbiome or what are you testing?

Dr. Urvi Shah: So when we think about the analysis for microbiome, I would think about it in three broad categories. One would be looking at microbiome diversity. That gives an understanding of just overall gut health, generally speaking.

When we look at diversity, we're just looking at the variety. So diversity is like what is a rainforest compared to a plantation, where there are a lot of species of birds, animals, and plants compared to a plantation that may have one or two species.

So we want a more diverse microbiome, and that's what we're looking at.

But we're not looking at the specific species when we look at diversity in terms of which species are there. And then when we look at the types of species or genera of microbes, we're thinking about are the healthier butrate producers increased or what is the quantity of those? So that's another thing.

And then the third thing would be the metabolites made by these bacteria. So things like short chain fatty acids is how much of those metabolites are they making? So we'll be looking at all three of these things with the samples provided by patients. And then we'll be able to understand and correlate some of that to say, is it associated certain subtypes of smoldering myeloma or with progression or things like that, because we would correlate that with clinical outcomes too.

Jenny: And then, one of the most important questions, who can join the study? So you mentioned MGUS patients and smoldering myeloma patients, but is there any other detail that you want to share about who can join and who can't join?

Join the NUTRIVENTION-2 Study

Dr. Urvi Shah: So I think one important thing is that patients who are taking too many supplements already, it might be hard. We would want you to stop that before joining the study, but we can discuss that once you put in the form or sign up. If the supplement is due to a medical indication where you absolutely need to take it, we might be able to think about an exception in that situation, but we have to think about which supplement it is.

But otherwise, the reason we want to avoid patients taking too many supplements is because sometimes many supplements can cause interactions and we don't want an unforeseen or unexpected side effect like you know rarely something like liver failure or something to develop when you're on so many things that interact. So just to be safe we're trying to avoid having patients taking too many things and also then we don't fully understand what is really having the effect on the microbiome.

So I would say that's one of the main criteria that if you're not willing to stop and you take like 20 supplements, then you're unlikely to be able to go on the study. But other than that, if you're willing to be open or flexible to seeing what absolutely is needed versus things that you can stop just for the period of the study, like it's a few weeks long and then you can resume whatever you were taking after, then that would be fine.

Jenny: And then if you are on treatment or have had treatment for smoldering myeloma, can you join?

Dr. Urvi Shah: Yes, as long as you're not currently on treatment, we’re having patients join with smoldering myeloma. We have broadened it to allow patients who may have had prior treatment, but we prefer that at the current time you're not on treatment. But if you had treatment previously, but as long as you're not on treatment currently, it would be okay to join.

Jenny: Yeah, that makes a lot of sense. You've had some participants in the trial so far. Do you have any comments about how they feel on this study?

Dr. Urvi Shah: So I think we have not yet analyzed all the data because the study is ongoing. But I think that what we have seen with other studies and just by word of mouth, what patients have told us is some of them have felt like, we have more energy or we feel less fatigued or we feel better. And so we're going to continue doing this longer.

I do think that patients sometimes do see direct benefits for themselves. And since we're covering the dietitian visit and all of these things on the study, it's an opportunity to also meet with a research dietitian, which otherwise would not be possible.

Jenny: Well, I just think this is such a great idea because obviously, we jumped in to say, yes, we want to support you in running this study. Our patient navigators are doing some of the phone calls to see if patients can qualify and can't qualify. We're sending that information to you, and then the patient connects with you and goes from there.

Dr. Urvi Shah: Yes.

Jenny: When I was first diagnosed, I asked the dietician what should I be eating? And they had nothing to say. So I'm like, okay, this is, I'd like a little more information about what would be helpful and what would be harmful and should I be worrying about my diet?

There's kind of like a cohort of people (or researchers) who say, well, they're cancer patients, so just don't bother them about what they're eating, but because they're already dealing with a lot. But if you are thinking about what you can do to improve your situation, trying something like this is an easy thing to do.

Dr. Urvi Shah: Exactly. We really do think - and participating will also help us answer the questions you have all been asking regularly. So when we have data from a hundred smoldering myeloma patients, the microbiome and also the effects of these interventions, we're able to explain or tell you like these certain microbiome patterns are associated with increased progression risk or versus not.

And then how can we modulate them and whether it's these interventions or designing new interventions from the data that we get to think about what could be the next one to design. So I think that this would be incredibly helpful for both patients and for researchers to be able to move to the next step of how do we intervene beyond these things to help patients.

And so if it's possible and you have smoldering myeloma and you're open to taking a little bit of time to participate in this study, we'd really welcome your participation and happy to guide you through whatever questions you may have as well.

Jenny: I think it's just fantastic. And I think everybody who has smoldering myeloma or MGUS should join the study. It's just such an easy way to get answers. This is really one of the reasons that we created HealthTree was because we wanted to see these types of interventions and really prove the concepts.

We don't want patients taking supplements they don't need to spend money on when it's not doing any good, but we want them to be using things appropriately when it is good.

Dr. Urvi Shah: Yes

Jenny: This study and the others that you have (in progress) will help answer those questions. So thank you for doing this study. We're excited to hear what you learned from it, and we invite all patients who qualify to join.

Dr. Urvi Shah: Exactly.

Jenny: Now, you mentioned that you have a newly diagnosed study also that you might want to talk about.

Dr. Urvi Shah: Great, yes. So I know that many times when I've talked about our NUTRIVENTION-2 studies, patients with myeloma reach out and say, What about studies for actual multiple myeloma and do you have any?

So we had one, the NUTRIVENTION-4 that is currently ongoing, but that one's looking at patients who are on maintenance therapy and like daratumumab or lenalidomide and a subset of them are getting the dietary intervention. So that study is about 70 % enrolled for the dietary part and hopefully in a year or two we'll have some of those results.

But what's more exciting is that patients who are newly diagnosed often have these questions and we really want to know upfront what does dietary changes do to the disease. And I don't think we know that because we don't know whether it makes it more stressful or it helps the patient. And I think that that's what we're trying to answer.

This study is going to be newly diagnosed patients getting Daratumumab, lenalidomide, bortezomib, and dexamethasone or Dara-RVD, as we say, induction chemotherapy. They should be planned for four cycles. They can be anywhere in the United States. And getting it, the study will be decentralized. We will enroll 200 patients.

Half of the patients will get the usual standard treatment with DARA-RVd without dietary intervention or discussion. And the other half will get meetings with a dietitian and some meals provided and the dietary intervention. And then we will measure things like response, quality of life, the microbiome, and these other biomarkers we've talked about to see if this affects outcomes or helps patients or not.

That study, we are currently in the process of working through the, you know, writing the study and opening the study and the logistics. I hope that the study will be open by about July or August sometime.

If a patient is within the first month of chemotherapy, they can enroll on the study after they finished more than one month, then they are already into the second or third cycle, then they would not be eligible anymore. So I would encourage any patient who is newly diagnosed in July or August and after to think about this study and really if you're open to participating. And if you know patients, if you are currently a myeloma patient, or if you are a coach and you know patients in the future that may be able to do this, spread the word and think about this study because this will really give us answers in the newly diagnosed space and how whether during treatment making these changes is something we should be considering or not.

Jenny: So important and I love the sharing suggestion because trying to find sometimes MGUS or smoldering myeloma patients or newly diagnosed patients is particularly hard and before they start treatment. spread the word with your myeloma friends.

Dr. Urvi Shah: Yes.

Jenny: Okay, last question. What would be your top five tips to incorporate a whole foods plant-based diet into your life?

Dr. Urvi Shah: That's a great question. And I do think that one thing to remember is that tastebuds change and adapt over time. So at this point, if you say like, really don't like broccoli or beans or something, that doesn't mean you don't like it for the rest of your life, but it can change over time. And I've seen that time and again with patients, family members, myself included, where there were things where I thought I didn't like and I would never eat, but now I really enjoy.

I've seen that for myself as well.

In terms of some of the myths or things to think about is that people think that frozen foods are not, frozen vegetables and fruits are not as healthy as fresh, but that's not the case. They may be even more healthy or the same because they are picked right when the vitamins and nutrients are fresh and they're frozen immediately.

So even if you don't have access to fresh produce, always having frozen fruits and vegetables in your freezer so you can heat them up or make a smoothie or something out of them, that's a great way.

Another thing is beans. So beans and plant protein is when people think about plant-based foods, they'll just think about fruits and vegetables. But I really want you to think about things like beans, which are other plant protein sources.

One cup of beans has about 15 grams of protein and 15 grams of fiber. So it can be a very nutritionally rich source of minerals, vitamins, and fiber and protein. So maybe adding a cup of beans daily to your life.

The next one would be whole grains. I think most people eat just white rice or wheat, but really not anything else. So trying to make a switch where every time you're eating a grain, you maybe diversify it, buy buckwheat, buy quinoa, buy barley, other ones.

Maybe every week you cook a different grain and you get used to them. And I think again, tastes, they're acquired tastes, but you would get used to them. And then in terms of vegetables, I think leafy greens are very important and trying to get some of those in daily, even mushrooms are another very healthy food. So thinking about them in your vegetables daily.

And then nuts and seeds. Nuts and seeds are also things that people don't think about as good snack options or things. Of course, nuts are calorie dense. So if you're trying to lose weight, they may not be the best. But if you're somebody who is on chemotherapy and wants to gain weight or needs to maintain weight, or even if you just want a healthy snack, thinking about nuts, seeds, very healthy and trying to incorporate them daily.

And then lastly, would say fruits. Most people, again, don't eat even one serving of fruit a day. If you could just add a serving and berries, especially, but any fruit, one serving a day would be important. I think basically I just talked about the five main areas. One would be plant protein sources, so beans, tofu, tempeh, seitan, whole grains, fruits, vegetables, and nuts and seeds.

If you could maybe think about consciously incorporating these things and going out of your comfort zone and picking things that you would not usually pick and then seeing what things really stick or things that you can try again. That will help with time.

Jenny: And also I remember you saying that the diversity, like trying to vary up the fruits and vegetables, not just eating the same ones you eat every day or you're accustomed to, not just for taste reasons, but for actually your microbiome diversity has an impact.

Dr. Urvi Shah: Yes, so that's a good point you brought up. There are studies that show that people who eat more than 30 plant foods a week compared to those who eat less than 10 plant foods have better microbiome health. And when they talk about the number of plant foods, they're talking about things like different plant foods, not the same one.

If you eat like green beans 30 times, that would be counted as one, but 30 different - like green beans, broccoli, chickpeas, herbs, things like that, that would count as different.

Jenny: Okay, I've tried this and it's good. It forces you to try things. We have a lot of children and our rule was always you have to take a bite of something. You don't have to eat the whole thing, but you have to at least take a bite. Even if you've had it before, it doesn't matter because what you're saying is true. Your tastebuds change. And sometimes you end up liking things you didn't like before.

Urvi Shah: That's great. For sure, I've had that happen to me so many times over the years now. And I've seen it with the patients on trials. The first month, you're adapting, and then your microbiome starts shifting too, and then you start craving some of the foods that now you're used to compared to before. So it takes a little bit of time, but you have to get over those first few weeks

Jenny: And it makes you feel better. So it's all good. Well, Dr. Shah, we are thrilled with what you're working on. We're so thankful somebody in the myeloma space has such intense focus on it because this is, to me, part of the future of myeloma care is educating patients about what they can actually do. And you only do this by obtaining the data. So we encourage patients to join your studies.

And especially the NUTRIVENTION-2 study that we talked about. With that, just thank you for everything that you are doing in this space.

Join the NUTRIVENTION-2 Study

Dr. Urvi Shah: Thank you so much Jenny, you've been really awesome and supporting this research and focus and I really look forward to continuing to work with HealthTree on these studies.

Jenny: Us too. And we'd like to thank our listeners for listening to the HealthTree Podcast for Multiple Myeloma. Join us next time to learn more about what's happening in myeloma research and what it means for you.