The REACH3 trial was a Phase 3 study evaluating the drug ruxolitinib for treating chronic graft-versus-host disease (cGVHD). The trial’s objective was to assess the safety and effectiveness of ruxolitinib in patients whose disease did not respond adequately to corticosteroid therapy. It compared outcomes for patients taking ruxolitinib against those receiving the best available therapy (BAT) selected by their physician.
Understanding Chronic Graft-Versus-Host Disease
Chronic graft-versus-host disease is a serious complication that can arise after an allogeneic stem cell transplant. The condition occurs when the donor’s immune cells, which form the new immune system (the graft), identify the patient’s own body tissues (the host) as foreign and begin to attack them. This immune response can lead to inflammation and damage in various organs.
The effects of cGVHD can manifest across the body, leading to a wide array of symptoms which can severely diminish quality of life. Patients may experience issues with their:
- Skin
- Mouth
- Eyes
- Joints
- Liver
- Lungs
Standard initial treatment for cGVHD involves corticosteroids to suppress the widespread immune response.
Many patients, however, do not achieve a lasting response with steroids alone. Some individuals are considered “steroid-refractory,” meaning their condition does not improve with corticosteroid treatment. Others are “steroid-dependent,” where they cannot reduce their steroid dose without the disease worsening. For this population, there has been a significant need for alternative treatments.
The REACH3 Trial Design
The REACH3 trial was structured as a randomized, open-label, multicenter study to ensure a robust comparison between treatments. The study enrolled 329 patients aged 12 years and older who had moderate to severe cGVHD. All participants had a history of their disease being either refractory or dependent on corticosteroid treatments.
Participants were randomly assigned into one of two treatment arms. One group, consisting of 165 patients, received ruxolitinib. The other group of 164 patients was treated with the best available therapy (BAT), where physicians chose from a predefined list of ten commonly used systemic treatments.
The main goal of the study, its primary endpoint, was to measure the overall response rate (ORR) at week 24. This metric was defined as the percentage of patients who achieved a complete or partial reduction in their disease symptoms by that time point.
Primary Outcomes and Safety Profile
The primary outcome was met, with the ruxolitinib group showing a significantly higher overall response rate at 24 weeks compared to the BAT group. Specifically, 49.7% of patients receiving ruxolitinib achieved a response, versus 25.6% of patients in the BAT arm.
Beyond the primary endpoint, the trial also assessed several secondary measures. One secondary outcome was failure-free survival (FFS), which measures the time until disease progression, the need for a new systemic therapy, or death. Patients on ruxolitinib experienced a significantly longer FFS, and a greater proportion of patients in the ruxolitinib group reported improvements in their symptoms.
The most frequently reported adverse events in the ruxolitinib arm were hematologic in nature. These included thrombocytopenia, which is a condition characterized by a low count of platelets, and anemia, a deficiency in red blood cells. These side effects were consistent with the known safety profile of the drug from previous studies.
Impact on Treatment Standards
The positive outcomes from the REACH3 trial directly influenced clinical practice and regulatory decisions. Based on the strength of the data, the U.S. Food and Drug Administration (FDA) approved ruxolitinib for adult and pediatric patients 12 years and older with cGVHD that has not responded to one or two previous lines of systemic therapy.
The trial established ruxolitinib as a new standard of care for patients with steroid-refractory or steroid-dependent cGVHD. Before these findings, treatment for this condition was often inconsistent, relying on various agents with limited high-level evidence to support their use. The randomized, controlled design of REACH3 provided the data needed to change treatment guidelines.
The availability of an effective, evidence-based therapy offers the potential to improve not only response rates but also the overall quality of life for individuals with cGVHD. The trial provides a validated option for a condition that previously had few reliable solutions.