Approaches to Treating Acute GVHD

Aaron C. Logan, MD, PhD:The standard method for prophylaxis against graft-versus-host disease [GVHD] using either a matched sibling or a matched unrelated donor is to use a combination of a calcineurin inhibitor, usually tacrolimus but sometimes cyclosporine, in combination with methotrexate, which is a cytotoxic agent that’s given to the recipient a few days after the transplant. Most regimens give it on days 1, 3, 6, and 11 after transplant, but some just give it on days 1, 3, and 6.

In coming up with an aggregate grade, that grading scheme goes from grade 0, which means no GVHD, through grades 1, 2, 3, and 4—grade 4 being the most severe and life-threatening in acute graft-versus-host disease.

When patients have grade 1, or mild graft-versus-host disease, that typically is going to manifest as a localized skin rash. We frequently use topical steroids to treat that. Patients who have more significant disease, grade 2 through 4, were patients who had steroid-refractory or steroid-dependent grade 2 through 4 acute GVHD.

On the study [REACH1], about 70 patients were ultimately treated with ruxolitinib for steroid-refractory GVHD. About 50 were evaluable based on the FDA analysis that led to the approval. And in that analysis, it was found that by 28 days after the initiation of ruxolitinib, the overall response rate was about 55%, with about a 30% complete response rate. The best overall response rate was over 70%, with a roughly 50% complete response rate as the best response seen on ruxolitinib.

This appropriately led to the approval of the agent [ruxolitinib] based on this relatively small number of patients. Because there are no other agents FDA approved for acute GVHD, this is definitely an advance for the field. As I mentioned earlier, the field had already started using ruxolitinib off-label because of its efficacy. Now we have it available because of the publication revealing data from the REACH1 study.

This study is going to be confirmed in what’s called the REACH2 study, which is actually randomizing patients with steroid-refractory or steroid-dependent acute GVHD between ruxolitinib or best available care, which is based on what their provider thinks the patient should receive. This study is actively accruing right now around the world and is expected to have some data available perhaps in 2020. Hopefully, we’ll see that ruxolitinib’s efficacy is borne out in that randomized study.

Transcript edited for clarity.