Ruxolitinib: a potential treatment for corticosteroid refractory acute graft-versus-host disease

ABSTRACT

Introduction

Allogeneic transplantation represents a potentially curative procedure for various lethal conditions; however, it is associated with serious immune mediated complications. The most serious complication is graft-versus-host disease (GVHD). Acute GVHD (aGVHD) is unresponsive to initial corticosteroid therapy in ~40% of cases. Corticosteroid-refractory aGVHD (CR-aGVHD) represents a significant unmet need with nearly 60% mortality in patients developing this state.

Areas covered

We review landmark trials which led to the US FDA approval of Ruxolitinb for the treatment of CR-aGVHD. Ruxolitinib phosphate is a Janus Kinase 1 and 2 inhibitor which inhibits pro-inflammatory signaling, and modulates T-cell subsets to an anti-inflammatory phenotype. Ruxolitinib was recently prospectively studied for the treatment of CR-aGVHD in the REACH1 trial, which added Ruxolitinib to corticosteroid therapy. This trial demonstrated favorable results with 73% of patients ultimately responding. Among responders, over 70% remained alive at 6 months. These results led to the US FDA to approve ruxolitinib as treatment for CR-aGVHD, the first approval of its kind.

Expert opinion

Ruxolitinib represents the standard option for CR-aGVHD. Future studies should identify patients less likely to respond to ruxolitinib and/or focus on a more targeted approaches to reduce infectious complications and cytopenias seen with this drug.

KEYWORDS:

• Stem cell transplantation
• hematopoietic
• graft vs Host disease
• GVHD
• ruxolitinib
• immunology
• acute GVHD
• steroid-refractory

Box 1. Drug summary

Table

Declaration of interest

M Hamadani is a Consultant for Incyte, Celgene, ADC Therapeutics and Pharmacyclics and receives speaker fees from AstraZeneca and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.