Gut Microbiome May Affect CAR-T Outcomes, But More Research Is Needed

While prior research showed that antibiotic use may be associated with poorer outcomes for patients with blood cancer who were being treated with CAR-T cell therapy, an expert on a more recent study explained that there were too many other factors beyond antibiotic use that could potentially contribute to these outcomes.

“If you wanted to sort of isolate, what is the effect of the microbiome, looking at the patients who received antibiotics, there's not a good way to do that, because they were confounded by all these other factors,” study author Dr. Michael Jain, associate member in the department of blood and marrow transplant and cellular immunotherapy at Moffitt Cancer Center in Tampa, Florida, said in an interview with CURE®.

Jain and his colleagues analyzed the gut microbiome (which could be drastically altered by antibiotics) of 172 patients with relapsed or refractory non-Hodgkin lymphoma who were being treated with CAR-T cell therapy at Moffitt, the University of Texas MD Anderson Cancer Center in Houston, or two other hospitals in Germany.

Their findings showed that patients who were taking a broad-spectrum antibiotic before CAR-T cell therapy tended to have less microbiome diversity and poor outcomes to treatment. However, these findings could also be driven by the fact that the group of patients who received antibiotics tended to have a higher tumor burden and a more suppressed immune system.

“What we found in this multicenter (study) was that, in fact, the patients who got antibiotics had very changed (and) dysregulated microbiomes after getting those antibiotics,” Jain said. “But they were also patients who had really high tumor burdens and their immune systems were really dysfunctional, which is probably why they got an infection in the first place needing the antibiotics.”

Of note, CAR-T cell therapy is an immune-driven treatment for non-Hodgkin lymphoma and other blood cancers. It involves harvesting a patient’s immune (T) cells, engineering them to find and fight cancer and then infusing them back into the patient. The gut microbiome also plays a role in the immune system, as, according to the National Institutes of Health, the gut microbiota that live in the intestinal tract play a key role in regulating when immune cells should activate — a concept known as “immune homeostasis.”

“One of the greatest interfaces between our immune system and what we call antigens, or things that are foreign to us, is all the bacteria that live in our bodies,” Jain explained.

Since there were these other factors that could affect CAR-T cell therapy outcomes, the researchers on the study then decided to analyze patients who received either no antibiotics or low-risk antibiotics before treatment. They found that patients who had a higher level of Bifidobacterium longum — a bacterium found in the gastrointestinal tract — tended to have an improved overall survival rate after CAR-T cell therapy.

Additionally, the researchers found that Bacteroides eggerthii was associated with a higher response rate to CAR-T cell therapy, while Bacteroides stercoris was associated with a lack of response.

However, Jain noted that there is not yet an adequate way that a person can change their microbiome through foods or additional supplements. Instead, patients should focus on just eating as healthily as possible.

“Diet is a very human thing. We think that a diet or what we eat profoundly affects the outcomes that we're going to get. And I think that's true,” he said. “But we don't yet know enough about the exact specifics of how to do that for any one medical situation, particularly in the field that I treat, which is CAR-T cell therapy, for lymphomas. And so, what I encourage my patients to do is to eat healthily, and we have dieticians, that other people that can help them with that process.”

Looking forward, Jain mentioned that he hopes to see a better intervention for improved gut microbiome health — and he thinks that is a real possibility based on the research surrounding the topic, not only in cancer care, but in health care in general.

“I think the fact that so many people are interested in this field, and there's so much energy and ideas going into new ways to improve this, I think that we will be not that far off from being able to productively modulate these factors to try and improve patient outcomes, which is really what we're always here for, trying to, in any way we can, increase the number of patients who are cured by our therapies,” he said.

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