Novel Treatment Approaches for GVHD
An esteemed panel of experts overviews new approaches being explored for treating graft-vs-host disease.
Transcript:
Preet M. Chaudhary, MD, PhD: Let’s talk about some of the exciting new approaches for GVHD [graft-vs-host disease] prophylaxis and treatment.
Eric Leon Tam, MD: It’s a constantly evolving area of investigation and research. At the Tandem Meeting in Orlando, Florida, [in February 2023], there was a lot of new basic scientific research into chronic GVHD and the mechanisms behind it because it’s not so simple as just 1 single pathway. It’s the entire immune system being activated, so there are multiple targets that need to be taken into account and oftentimes a multimodality approach would be very beneficial for these patients. One of the more promising studies has been looking at a CSF1R [Colony-stimulating factor 1 receptor] inhibitor, which inhibits macrophages and viral glass formation and scarring, and because that’s the hallmark of chronic GVHD. That’s currently in phase 1 and phase 2 studies and I think they have the interim analysis coming up for that.
Preet M. Chaudhary, MD, PhD: That will be very exciting if someday there’s an agent which can reverse the control of fibrotic GVHD.
Eric Leon Tam, MD: What we really don’t know is combination therapy, how well and which ones work well together, so once we start combining and looking at ruxolitinib [Jakafi] with a ROCK2 [Rho-kinase 2] inhibitor for example…
Lakshmi Savitala-Damerla, PA-C: There are some institutions already doing that. City of Hope Comprehensive Cancer Center in Duarte, California, for example, does the Jakafi and the belumosudil [Rezurock] combination.
Eric Leon Tam, MD: They’re doing it out of a clinical study but it seems safe.
Preet M. Chaudhary, MD, PhD: Especially because if they are targeting 2 different pathways then if you block both pathways you’re likely to have a more additive and synergistic effect. Let’s also talk a little bit about the clinical biomarkers because Lakshmi, as you mentioned, that’s one of the areas of need here where we don’t have good biomarkers to diagnose GVHD.
Eric Leon Tam, MD: We’ve been looking at clinical biomarkers for a long time now in GVHD. I think the 2 that have come up to be the more prominent have been the ST [suppression of tumorigenicity] and REG2 [regenerating protein 2], I think right?
Lakshmi Savitala-Damerla, PA-C: Right.
Eric Leon Tam, MD: There are companies out there that you can send out to follow and track these levels. They’ve been shown to have some fairly good correlation both in terms of predictive, whether they’re going to develop chronic GVHD, and also while you’re treating as these biomarkers come down it may show that there’s a laboratory improvement. Sometimes it’s very difficult to show clinical improvement over these months of time. So there’s definitely still an area of unmet need and definitely we need more clinical markers to be able to track different sites of disease as well because these don’t always track different areas.
Lakshmi Savitala-Damerla, PA-C: I think the more we venture into this and try to expand, the more we understand that there’s a lot more that we don’t understand about the pathways and what to target.
Transcript edited for clarity.
