Preventing GVHD With Itacitinib in Stem Cell Transplants

Uday R. Popat, MD, professor of medicine in the Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses a phase 2 trial exploring the use of the JAK inhibitor itacitinib (INCB039110) combined with post-transplant cyclophosphamide (PTCy) and tacrolimus to prevent graft-vs-host disease (GVHD) in patients undergoing a myeloablative fractionated busulfan regimen.

This innovative approach aims to reduce non-relapse mortality and improve transplant outcomes by targeting GVHD.

Transcription:

0:10 | The main reasons for stem cell transplant failure are relapse of the original disease and treatment-related mortality, or non-relapse mortality, due to the transplant. To improve outcomes, the best thing—or the only thing—to do would be to reduce non-relapse mortality and reduce the relapse rate.

0:37 | In this abstract, we aimed to reduce non-relapse mortality by reducing the incidence and severity of graft-vs-host disease in patients undergoing allogeneic transplantation. So we have, systematically over a period of time, developed consecutive protocols to achieve this. First, we lengthened the duration of the regimen, [which we call] a fractionated busulfan regimen. Instead of giving it over a 4-day period, we give it over a 3-week period.

1:19 | What this allows us to do is reduce the toxicity of the treatment and enhance non-relapse mortality. It also allows us to deliver a myeloablative dose of chemotherapy to older patients, which in turn reduces the relapse rate.

1:43 | In addition to fractionating the busulfan, we added post-transplant cyclophosphamide to reduce graft-vs-host disease. In this study, we took the next step by adding itacitinib, which is a JAK inhibitor. It is known that JAK inhibitors are useful in the prevention and treatment of graft-vs-host disease. We hypothesized that a JAK inhibitor might also be useful in the prevention of graft-vs-host disease, reducing non-relapse mortality and further improving our treatment regimen