Efficacy of a JAK2/mTOR Inhibitor Combination in Controlling Acute Graft-vs-Host Disease

By The ASCO Post Staff
Posted: 8/8/2024

Adding a Janus kinase 2 (JAK2) inhibitor to standard immunosuppressive drugs may not improve prevention of acute graft-vs-host disease in patients with hematologic malignancies undergoing treatment with allogeneic hematopoietic cell transplantation, according to a recent study published by Pidala et al in Blood.

Background

Hematopoietic cell transplantation may offer a potential cure in patients with hematologic malignancies; however, between 10% and 20% of patients who receive stem cells from a donor through allogeneic hematopoietic cell transplantation develop acute graft-vs-host disease within the first 100 days following transplant. This condition occurs when a donor’s immune cells identify the patient’s cells as foreign and attack them. Apart from disease recurrence, graft-vs-host disease can be life threatening and greatly impact a patient’s quality of life posttransplant.

While JAK inhibition is often effective in treating graft-vs-host disease—the JAK1/2 inhibitor ruxolitinib is indicated for the treatment of refractory graft-vs-host disease—the researchers conducting the recent trial addressed whether JAK inhibitors could have a role in graft-vs-host disease prophylaxis. JAK2 inhibitors are capable of turning off the JAK2 gene—which promotes inflammation and contributes to the development of graft-vs-host disease.

“JAK inhibitors are active in treating [graft-vs-host disease] that does not respond to steroids,” explained senior study author Brian Betts, MD, Vice Chair of Strategic Initiatives for Transplant & Cellular Therapy at the Roswell Park Comprehensive Cancer Center. “But the question over the past 10 years has been whether JAK inhibition could prevent [graft-vs-host disease],” he added.

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