ASH 2024 | Investigating fecal microbiota transplant as a strategy to mitigate infection and GvHD following TCT

So I just showed you that we have some very promising data for the treatment of acute graft-versus-host disease, but we believe that in fact the story of the microbiome therapy in the field of hematological malignancies, and in particular in patients that are going to receive chemotherapy, will not end here. In fact, I have been invited to discuss this topic during The ASH in San Diego this year, and we have more and more data now that come out. So I just show you, it seems to be effective to treat acute graft-versus-host disease, not only for the GI involvement, but also we have some response in the skin and the liver. But maybe we should move this a bit earlier or not as a curative treatment, but as a preventive treatment. So we have some studies that were published this year where we try to evaluate FMT as a tool to reduce the rate of infection after allogeneic stem cell transplantation. Unfortunately, it was a negative result, but there was also a very broad endpoint taking into account not only bacterial but also viral and fungal infection that might explain why it was not a successful clinical trial. 

Nevertheless, we have some more studies that are ongoing. We have some reports that show that we can use FMT to eradicate multidrug-resistant bacteria. We have also some studies that show that we give some feces after stem cell transplantation, it allows to restore the microbiome diversity. In fact, there is another clinical trial that is ongoing in Europe that plans to include more than 300 patients that will evaluate the use of pool microbiota transplantation using some pills, MaaT033, to the patients or placebo to restore the microbiome diversity and to improve patient overall survival. This is for patients with stem cell transplantation. 

In the field of cellular therapy, we have also the hot topic of the CAR T-cells. We know that we have more and more data now that show that the microbiome seems to impact the response to the CAR T-cells, in particular for anti-CD19 CAR T-cells, for lymphoma or acute lymphoblastic leukemia. It seems that it’s not just a correlation, that we have some mechanistic effect and we have an impact of the microbiome on the fitness of the CAR T-cells on the immune bystander. In fact, there is an ongoing clinical trial in the MD Anderson Cancer Center that tries to evaluate the use of FMT to improve the response rate of the CAR T-cells, so we think that it will change the field of hematology. Now in the next years, when you are going to use cellular therapy, immunotherapy, maybe you will need also to do some gut microbiota manipulation using a microbiome therapy product, FMT, or maybe some new drugs or new strategy based on the food taken by the patients, some prebiotics, but only the future will tell us what is the best treatment, what is the best microbiome therapy for our patients, and how it will improve the outcome of our patients.

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