ONCAlert | Upfront Therapy for mRCC

Therapies Under Investigation for GVHD

Targeted Oncology
Published Online:12:35 PM, Mon August 26, 2019

Claudio Anasetti, MD: Ruxolitinib is an inhibitor of both JAK1 and JAK2. It’s downstream of the IL-6 receptor, IL-1 beta, and IL-23 receptor, and it’s required for induction of Th17 cells that are important for the pathogenesis of both acute and chronic graft-versus-host disease [GVHD]. Work has shown that JAK1 and JAK2 are important in GVHD pathogenesis. Therefore, it is possible that a single JAK1 or single JAK2 inhibitor may be able to prevent or treat GVHD with less toxicity. Single inhibitors will be developed, but they’re all in early stages at this point.

Because JAK1 and JAK2 are downstream of the IL-6 receptor, it is rational to block that receptor for GVHD prevention. Work has actually supported that concept, and a randomized trial has been completed. The data from that trial is outstanding and is expected later on this year.

There are other agents that are of interest for the prevention and treatment of GVHD, such as sirolimus, which is an mTOR inhibitor, and bortezomib. Each of these 2 classes of agents has been tested in individual settings, but, right now, the exact use for the management of GVHD—prevention or treatment, acute or chronic—has not yet been defined.

A number of other agents are in development for the management of acute GVHD, including alpha-1 antitrypsin. This is a very safe agent. The question really is whether it’s going to show efficacy in appropriately conducted clinical trials.

Transcript edited for clarity.

Claudio Anasetti, MD: Ruxolitinib is an inhibitor of both JAK1 and JAK2. It’s downstream of the IL-6 receptor, IL-1 beta, and IL-23 receptor, and it’s required for induction of Th17 cells that are important for the pathogenesis of both acute and chronic graft-versus-host disease [GVHD]. Work has shown that JAK1 and JAK2 are important in GVHD pathogenesis. Therefore, it is possible that a single JAK1 or single JAK2 inhibitor may be able to prevent or treat GVHD with less toxicity. Single inhibitors will be developed, but they’re all in early stages at this point.

Because JAK1 and JAK2 are downstream of the IL-6 receptor, it is rational to block that receptor for GVHD prevention. Work has actually supported that concept, and a randomized trial has been completed. The data from that trial is outstanding and is expected later on this year.

There are other agents that are of interest for the prevention and treatment of GVHD, such as sirolimus, which is an mTOR inhibitor, and bortezomib. Each of these 2 classes of agents has been tested in individual settings, but, right now, the exact use for the management of GVHD—prevention or treatment, acute or chronic—has not yet been defined.

A number of other agents are in development for the management of acute GVHD, including alpha-1 antitrypsin. This is a very safe agent. The question really is whether it’s going to show efficacy in appropriately conducted clinical trials.

Transcript edited for clarity.
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