Advances in the Prevention of GVHD

— Ryotaro Nakamura, MD, discusses current and emerging strategies

MedicalToday

Graft-versus-host disease (GVHD) remains one of the most common complications of allogeneic stem cell transplantation (ASCT). Unless the patient's donor is an identical twin, a patient undergoing ASCT will receive some type of GVHD prevention. There is no standard regimen for the prevention of GVHD, and different combinations of medications are given at different institutions.

In this exclusive video, Ryotaro Nakamura, MD, of the City of Hope Comprehensive Cancer Center in Duarte, California, reviews the current and emerging strategies in GVHD prevention.

Following is a transcript of his remarks:

GVHD prevention ... I think the one big thing happening in the field is the performance and the application of a procedure or process called post-transplant cyclophosphamide, or PTCy. And as you know, it originated from Johns Hopkins for haploidentical donor transplant, but quickly applied when the donor is matched. And so far, for haplo transplant, this has really been the standard approach at this moment.

For the match donor transplant, we don't necessarily know this is the best. This looks [to be] one of the best, and now a large phase III study comparing between the standard methotrexate versus post-transplant cyclo approach, which combined with calcineurin inhibitor, that prospective phase III study is being completed. And we are expecting the first data to be available in the next few months.

After methotrexate and cyclosporine, there are a number of drugs that are being added to this historic backbone -- one example [is] abatacept [Orencia] that was recently approved by the FDA for the indication of GVHD prevention. It is combined with methotrexate and had pretty good results in the mismatched donor transplant, which, again, I think the PTCy has been effective. So, eventually there could be a study comparing these two methods.

Another drug that is also being added to the historic GVHD regimen is a JAK inhibitor. And we have to talk about that for therapeutics, but Jakafi, or ruxolitinib, has been approved now for both acute and chronic GVHD treatment. But this has been used also upfront as a prevention of GVHD. One study actually is from City of Hope -- we did kind of an upfront use of Jakafi in patients with myelofibrosis. So, this was more or less a preventive type of approach.

Incyte, the company, also is supporting some studies using itacitinib, so that's another JAK-1 inhibitor, again, in combination with historic GVHD prophylaxis. So, [study of these types of drugs] combined with the historic backbone will probably continue.

We are also doing a study with Fred Hutch and a few other centers testing ustekinumab [Stelara]. That is a monoclonal antibody approved for psoriasis, but [there has been] good pilot data in preventing GVHD, so now we are doing that randomized trial.

So, again, we don't think PTCy is the best forever, and ... people are trying to, you know, come up with better new ideas.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.