EBMT 2023 | An update on the use of FMT for the treatment of steroid- and ruxolitinib-resistant acute GvHD

Over the last decades, a lot of studies established a link between the microbiome and the outcome of patients after allogeneic hematopoietic [stem] cell transplantation. Based on these findings, there were some experiments to evaluate the use of FMT so fecal microbiota transplantations to treat dysbiosis in particular for patients that have acute graft-versus-host disease and to see if this is effective to improve the outcomes. There are several small case reports with some very good results based on these first results. After some studies, there was one study that was published two years ago in 15 patients with very good results since the long follow-up, where we have six patients that remain in complete response from a very severe GI acute graft-versus-host disease. We also performed a Phase II clinical trial where we included 24 patients and we reported an overall response rate over 50% before day 28. This response rate translated into higher overall survival in patients that respond compared to non-responding patients. So, for now, there are some new studies that evaluate FMT in particular, in patients that are refractory to ruxolitinib since this is a standard second line treatment for graft-versus-host disease. In addition to the treatment of acute graft-versus-host disease, there is also a clinical trial that try to evaluate FMT as a preventive treatment to restore dysbiosis after allogeneic stem cell transplantation to reduce the risk of patients to develop graft-versus-host disease and to improve the outcome. But so far, we don’t have any data regarding the efficacy in this setting and we expect to have some more to share in the next few years.

In addition to the 24 patients that were able to treat into the Phase II clinical trial, we were able to treat 81 patients with fecal microbiota transplantation within the compassionate use programs. All patients were resistant or dependent to steroids. In addition, we have 81% of the patients that were also resistant to ruxolitinib. So, these were some highly pretreated patients with the median of two lines of treatment for acute graft-versus-host disease. Of course, all patients have a GI involvement for acute graft-versus-host disease. The overall response rate for the GI tract was 56%. If we look at the overall response rate also with the skin and liver involvement, we have a 49% overall response at day 28 highlighting that FMT is not only effective for the GI but also, we have some response for the skin and liver. Regarding the outcome of the patients, in responding patients, we have a 59% overall survival at one year compared to 14% of overall survival for the non-responding patients. In terms of safety, the overall safety was very good compared to the historical data in these very heavily pretreated and fragile populations. We have a few sepsis that were reported, but we did not report any pathogen transmission from the FMT project and really seems that we have now some very good results with the ongoing Phase III clinical trial that evaluate this FMT in the setting of steroid and ruxolitinib resistant patients.