Ketogenic Diet During CAR-T Therapy for DLBCL | Christopher D'Angelo, MD | #ASH24

Hi, my name is Christy Angel and I'm a lymphoma and multiple myeloma specialist at the University of Nebraska Medical Center in Omaha, Nebraska. Another abstract that was very exciting, it was at the Ash Plenary Session and it was based on some mouse modeling work done on looking at different diet strategies during CAR T cell therapy. And the researchers from this group noted that offering mice different diets actually and then infusing a CAR T cell therapy for those mice that had the lymphoma showed that certain diets actually seemed to work a little bit better and actually make the CAR T work better. In particular, the ketogenic diet, which we've heard lots about in lots of different metabolic diseases. And what they saw here is that the ketogenic diet, when given along with a CAR T cell product, actually made the CAR T cells work better. And what the researchers did, which is really exciting here, is they traced the mechanism by how this works. They saw that the ketogenic diet produced a ketone, something called beta hydroxybutyrate. And that is something that gets incorporated into the energy cycles of all your cells, in particular your mitochondria, which is the powerhouse of your cell. And so they saw that in these mice that they had higher levels of this beta hydroxybutyrate. They then took human samples from those patients that received CAR T and they saw that the higher CAR T expansions that were happening in their blood after they got CAR T cells, they also correlated with higher levels of this ketone, beta hydroxybutyrate. They then took that ketone and infused it and they saw that it was actually helping the CAR T cells work better. They took those CAR T cells and incubated them with beta hydroxybutyrate and it worked better. And it looked like it was by kind of stimulating them to be more productive, produce more cytokines and proliferate a little bit more too. So this is one of these first really exciting experiments to show that the diet that you choose can lead to direct metabolic changes that actually power and make some of our immune therapies work better. So a real wonderful way and lots of different ways that we could explore this in the future, but just kind of a nice proof of concepts suggesting that even simple things like our diet can actually have profound effects on some of our immune therapies. When you use something like a ketogenic diet, you are sort of selecting for alternative fuels and metabolite products that are produced. So the ketogenic differs from a traditional diet by being much lower in carbohydrates, for example, and much higher in fats. These fats produce slightly different metabolic breakdown products and so those get incorporated into cell energy processes differently. And one of the things that was observed here is it goes into something called the citric acid cycle, which is a different metabolic and a key metabolic pathway for all of your cells in the human body. But it uses this different and by using and incorporating this strategy a little bit more, it changed some of the cells ability to activate a little bit more. I think it's important to know that this is just mouse work right now. And so I don't know that everyone needs to be moving towards a ketogenic diet immediately when it comes much more research needs to be done to know for sure if that's truly something that's an effective strategy. But what is exciting to know is that I think it's important to continue to ask and talk about diet strategies, supplement strategies, talk with your doctor about them and see what's and follow their best guidance to to come up with something that makes sense, that offers alternative kinds of therapies that can improve immune boosting.