Graft-versus-host disease, or GvHD, remains a key issue after allogeneic stem cell transplantation. Obviously, we have to distinguish acute and chronic GvHD. Thanks to the NIH consensus and efforts, we are able now to clearly make the difference between these different clinical entities, and that has allowed to improve the quality of research, but recently also to bring some new treatments into GvHD...
Graft-versus-host disease, or GvHD, remains a key issue after allogeneic stem cell transplantation. Obviously, we have to distinguish acute and chronic GvHD. Thanks to the NIH consensus and efforts, we are able now to clearly make the difference between these different clinical entities, and that has allowed to improve the quality of research, but recently also to bring some new treatments into GvHD.
If I focus on acute GvHD, actually the first line treatment remains high-dose steroids. Unfortunately, we don’t have better options today. However, we know very well that roughly half of the patient will not be able to respond or will be steroid dependent. And this is where, in the last 3 or 4 years, we’ve seen the advent of ruxolitinib, which has become a standard of care for steroid-refractory acute GvHD. So that’s really good news. The bad news is that not everybody is able to respond to ruxolitinib, and some patients will lose the response to ruxolitinib. So we end up with a new group of patients who are very hard to treat actually, the ruxolitinib resistant or refractory or dependent patient. And here we really need new options.
And this is why I felt that we are fortunate enough we’ve seen at this EBMT 2024 annual meeting in Glasgow some new options, especially the modulation of the microbiota. And I was really impressed by the results, but also the safety profile of an experimental agent that was presented as part of the oral sessions on a large series of 140 patients who were treated in an early access program with fecal microbiota therapy based on the agent called MaaT013. And the results are really impressive. You have an overall response rate at day 28, which is above 50%, roughly 60, almost 60%, especially in those patients who received and failed ruxolitinib. And these are patients who received a median of two lines of therapies, prior therapies for GVHD, up to six lines. And interestingly, almost all of these responses, more than 90% are either CRs or VGPRs. And that is going to correlate with an improved survival. So really great news coming from the microbiota modulation. And I’m very excited about this.
Now looking into chronic GvHD, which of course is another matter of concern, especially with its impact on the quality of life of the patient. We’ve also seen the advent of ruxolitinib in steroid-refractory chronic GvHD. Very good news. But the other good news is that we have now another agent, different mechanism of action, namely a ROCK2 inhibitor belumosudil, which is proving to be a key player in the field of chronic GvHD with a very high response rate in heavily pretreated patients having advanced stages of chronic GvHD more than 70%. And interestingly, all localizations are going to respond, including longer chronic GvHD. And this has been always a nightmare, I would say, because it’s a totally terrible situation for patients.
This is why I’m very optimistic when it comes to acute GvHD, with the advent of JAK inhibitors, the advent of microbiota modulation. With chronic GvHD, JAK inhibitors, ROCK2 inhibitors. I think the field is moving really nicely in the right direction. And we’ll get there. We’ll be able, I think, to get rid of the severe and most debilitating GvHD situations. And obviously this will allow to improve not only the survival but also the quality of life of the patient, and that is the ultimate goal.
