When it comes to advances in graft-versus-host disease, I think we need to distinguish several aspects.
First of all, prevention of GvHD, and I believe today, the highest level of enthusiasm is about how to refine the use of post-transplant cyclophosphamide with or without ATG to further improve GvHD prophylaxis, and control. The second parameter is about frontline treatment of GvHD whether acute or chronic...
When it comes to advances in graft-versus-host disease, I think we need to distinguish several aspects.
First of all, prevention of GvHD, and I believe today, the highest level of enthusiasm is about how to refine the use of post-transplant cyclophosphamide with or without ATG to further improve GvHD prophylaxis, and control. The second parameter is about frontline treatment of GvHD whether acute or chronic. And unfortunately for the time being, it looks like that high-dose steroids remain the backbone and the key players in the frontline setting. However, things are really nicely moving when it comes to treating acute GvHD beyond first line and for treating chronic GvHD beyond first line; in another word, second-line, third-line in the refractory setting. So for refractory acute GvHD, steroid-refractory GvHD, I think we’ve seen some interesting and positive results with ruxolitinib, JAK2 inhibition and I think the experience is accumulating now with ruxolitinib as a treatment for steroid-refractory GvHD. However, it doesn’t solve all the problems.
And this is where I’m very enthusiastic about the impressive results that are generated with microbiota modulation and fecal microbiota transfer, which is allowing to salvage a patient with highly advanced acute GvHD. So this is really good news in terms of chronic GvHD, I think the field has seen the advent and even approval by the FDA in the last three, four, five years of three drugs. Ibrutinib first, based on a single arm Phase I/II trial, then we have ruxolitinib based on the REACH3 trial, and more recently we’ve seen belumosudil.
So, on one hand, you have BTK inhibition, you have JAK inhibition, and now you have ROCK2 inhibition. So, with all of these tools, I think in the near future, we will be able to further, I think, optimize the management of patients with GvHD, especially beyond the first line. And this is really… very reassuring because for the last two, three, four decades, we’ve been really struggling trying to bring new drugs into the GvHD space, but many trials failed. And now we have drugs approved, which is really great.
