EBMT 2025 | Advances that have been made in the treatment of acute & chronic GvHD

Graft versus host disease, whether acute or chronic, remains a matter of concern. I think we’ve done huge advances when it comes to prophylaxis, thanks to the advent of the so-called post-Cy, post-transplant cyclophosphamide, which is now increasingly used. We’ve seen recently also the combination of post-transplant cyclophosphamide and ATG. And this is even allowing to decrease incidence of acute and hopefully chronic GVHD. Nevertheless, despite improvement in prophylaxis, we still have patients struggling from acute GVHD, but also from chronic GVHD.

If we think about the acute GVHD space, actually the first-line treatment remains high-dose corticosteroids. Ruxolitinib has been approved for the treatment of steroid refractory acute GVHD. But unfortunately, we do have patients who do not respond to ruxolitinib. We do have patients who respond but will lose their response to ruxolitinib, and we do have patients who are intolerant or develop side effects after ruxolitinib. So we end up in a sort of a third group of patients who are the ruxolitinib resistant or intolerant. And we’re fortunate that in this population, now we do have also effective tools, not approved yet, but definitely positive results with microbiota modulation, namely the MaaT013 fecal microbiota product, which is proving to be highly effective, feasible, and safe in this population, allowing to achieve a very high response rate, including a majority of complete responses, which translates into a survival advantage in this ruxolitinib-resistant population. And obviously, this is a very most welcome newcomer into the space.

When it comes to chronic GVHD, again, we knew about ibrutinib, a BTK inhibitor approved in the US, not in Europe. We know that ruxolitinib is also approved in the chronic GVHD, steroid refractory chronic GVHD setting, thanks to their so-called REACH3 trial, and it is more and more widely used. Recently, we’ve seen the publication of the results of the Agave trial with axatilimab, which is a monoclonal antibody targeting CSF1 receptor. But I think there is a lot of excitement about another agent which was approved in the US a couple of years ago, approved already in the UK, in Canada, in China, and hopefully soon in the EU, and this is belumosudil, which is a ROCK2 inhibitor. And what is really exciting about Belumosudil, and by targeting this ROCK2 pathway, is that you can act on both inflammation, so the inflammatory component of chronic GVHD, and on fibrosis. So you are like hitting two birds with one stone. And the results from the registration trial, which are already well known, could show more than 70% overall response rate, and all organs can respond, including the lung, with an excellent safety profile.

And more recently, we’ve seen the advent of real-life use of belumosudil as part of compassionate use programs here or there. And for instance, in our own French compassionate use program, which is about to be published very soon, we’ve seen a very high rate of overall response rate, similar to the registration trial, including up to 14% of complete remission. And this is a population who received and did not respond to several lines of prior therapy to chronic GVHD.

So you can see, I feel more and more excited about this GVHD space, whether acute or chronic, because after three or four decades of, I would say, failures, let’s call it like this, now, we do have effective drugs, effective protocols, I would say, to manage these patients. And we owe all this to a better understanding of the pathophysiology of GVHD. So really, at some point, hopefully, we hope to get rid of GVHD with better prophylactic regimens. But for the time being, I think it is good to have all of these new options. And of course, if we can move these new options into earlier in the natural history of GVHD, I’m convinced that we will be able to achieve even better results and GVHD control.

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