Building a Dietary Evidence Symposium | Urvi Shah, MD | ASH 2022

Hi, everyone. I'm Urvi Shah from Memorial Sloan Kettering Cancer Center. I'm a hematologist and oncologist on the myeloma service. I'm excited to share with you that for the first time at the American Society of Hematology meeting this year, we had a scientific symposium dedicated to building dietary evidence for hematologic malignancies. And I know this is what patients often want and ask questions about. So it is great that we were able to have this discussion and talk about how do we move this field forward. In this session, we had three speakers. We talked about how it is important because patients want these low-cost intervention opportunities and also how they could improve outcomes and the ability to tolerate drugs better. We had three talks. One was by Dr. Catherine Marinak, and she talked about metabolic factors in cancer with an epidemiologic focus. The second talk was by Dr. Matteo Bellone, and he talked about the microbiome and metabolomic markers with translational focus, so looking more at mouse models. And then the third talk was by me, and we discussed immune and clinical side of things like clinical trials and how do we do these studies in patients. So I'll discuss briefly about all three of these talks. So Dr. Marinak went over data on what's already known about diet and cancer in large population studies. So she talked about how we know in myeloma the risk of obesity, increasing cancer risk and maybe affecting outcomes as well. Also studies around diet can be sometimes hard to do, and we sometimes wonder, is everything associated in some way with diet? But what she discussed was it's sometimes more important to study dietary patterns than a single food group when you're looking at large population studies, because if somebody's eating more of something, they're probably eating less of something else, so you're not truly just looking at one item, you're looking at a change in a pattern. So with that, she talked about the EPIC Oxford study, which is a large study looking at how a diet can affect hemolygancy risk and showed that vegetarians had a significantly lower risk of developing hematologic cancers in that study. Additionally, she talked about the American Institute of Cancer Research guidelines too that discuss how it's important to share this information with patients. She also further went on to discuss a few of their studies that are going on at Dana Farber around intermittent fasting and metformin in the precursor state. The next talk was by Dr. Billone, and he talked about the microbiome and translational focus. So he does research around mouse models and looking at how the microbiome affects progression of disease and outcomes. One of his major papers that he has published has been in the myeloma space looking at how bacteria like Prevotella, Hepatolotica, and melaninogenica affect progression from smoldering myeloma to myeloma differently in mouse models. He expanded on this data and the next steps of what they're doing, looking at how this is affecting the immune system through the microbiome, and also next steps. So he showed some interesting data on how butrate levels delay progression of myeloma in mouse models as well. These were the short chain fatty acid butrate. What he did in the study was he fed the mice with butrate and showed that that delayed the progression compared to controls who did not get the butrate. So that was the focus of his talk. Then the third talk was the one that I spoke about the immune diet connection. There is a lot of data around this where in healthy populations we know that diet can affect the immune system. There is actually a very interesting study from the NIH looking at patients who are given 14 days of a vegan diet and 14 days of a ketogenic diet and asked to switch over. They looked at immune changes in these patients. The data is yet unpublished, though the original trial has been published. They looked and they saw that the vegan diet actually improved the innate immune response and antiviral response, which may be why we see less COVID in epidemiologic studies around plant-based dietary patterns, and that the ketogenic diet may have improved the adaptive immune response, which is a different mechanism of how the immune system works. Sometimes it may be that we have to understand where to use what, but I think the innate immune system is the most important because that's the foundation on which the other immunity works as well. Other things we talked about is how eating. A study showed that high fermented foods, about six servings per day, increased microbiome diversity, and this included fermented foods and drinks, and all of them were just six servings per day. We then went on to discuss how diet can be studied in three settings, in the prevention treatment and survivorship setting. In the prevention setting, we're talking about diet as a means to prevent cancer development. So in settings like MGUS or small ring myeloma, or even in lymphoma or leukemia where it would be monoclonal, B lymphocytosis, or asymptomatic CLL, or indolent follicular lymphomas, and how do we consider if diet could make a difference to dealing progression to the aggressive cancers. We discussed our new prevention pilot trial, and that ensured how patients on that study were able to adhere to the whole food plant-based diet, but also saw a change in the microbiome for an increase in beneficial bacteria. And stool butrate levels too, as well as changes in inflammation, insulin resistance, and cholesterol levels. We then talked about our new prevention three study, which is now enrolling, where we're looking at diet versus supplements versus placebo. The next part of the talk was looking at in the treatment setting. So in the treatment setting, I think, you know, can we use diet in combination with drugs like chemotherapy or immunotherapy to improve response rates or reduce symptoms and side effects and maybe MRD negativity rate. And obviously, this needs to be studied better. But one really interesting trial from in acute lymphoblastic leukemia, looking at a high risk B acute lymphoblastic leukemia patients, 40 patients were asked to eat a healthier diet, where they were asked to follow the USDMI plate recommendations and traffic light of what's good versus not. And they were also asked to calorie restrict a little bit by 10% by dietary base and also exercise a little more. So they were in a slight calorie deficit. What they showed is that actually these patients had a higher MRD negativity rate, meaning a higher response to their chemotherapy compared to those who did not do it in the historical control arm. So it wasn't a randomized study. So that's the issue with that study. But what they showed is compared to historical patients who never made any changes, they saw an improvement in response. They're actually now doing a randomized study called the ideal two trial. We then discussed the next setting, which was the survivorship setting. And in the survivorship setting, I think it's also very important where patients are now done with their treatment. And sometimes in some of the ARHEM malignancies, patients are on maintenance. And in other settings, patients are not on maintenance and they're only on observation. So can diet or lifestyle changes delay the risk of the cancer coming back or potentially even cure some patients? And in that, we discussed the example of our recent publication in clinical cancer research where in that study, we associated diet with the microbiome and with sustained MRD negativity in survivorship patients. So these patients were on lenalidomide maintenance. And we showed that patients on lenalidomide maintenance who ate healthier plant proteins had higher levels of diversity in their stool, higher stool butrate producers and higher stool butrate levels. And this was associated with higher sustained MRD negativity. This is obviously an association study. And I think more data needs to be looked into for this mechanism. And we have the Neutrovention IV study enrolling for that, where patients will be randomized to either daratumab or lenalidomide as a quality of life study. But in that study, the first 15 patients that go on each arm have the option to get three months of a diet and look at the effects of the immune system and diet together. And with that, we basically summarized all the trials that are ongoing in hemolygnancies and diet, not just in myeloma or lymphoma, but there's things in myeloproniferative neoplasms as well that are ongoing. We discussed how it's important to build this evidence for patients and how we could think about studying it as next steps. So I think more to come, a lot more to come because there was a lot of excitement and enthusiasm from people at the conference for this topic.