Ruxolitinib in Steroid-Refractory cGVHD and REACH3 Efficacy Data

EP: 1.Introduction: A 58-Year-Old Man With Moderate Steroid-Refractory cGVHD and Risk Factors for cGVHD

EP: 2.Overview of cGVHD Symptoms, Diagnosis, and Tools for Severity Assessment

EP: 3.Steroid-Refractory cGVHD: Risk Factors and Clinical Challenges

EP: 4.Treatment Options for Steroid-Refractory cGVHD

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EP: 5.Ruxolitinib in Steroid-Refractory cGVHD and REACH3 Efficacy Data

EP: 6.Real-World Efficacy Data for Ruxolitinib in Steroid-Refractory cGVHD

EP: 7.Ruxolitinib Adverse Event Data and Strategies for Managing Side Effects

EP: 8.Case Commentary and Considerations for Treatment and Management

EP: 9.Future Directions in GVHD

Case: A 58-Year-Old Man With Moderate Steroid-Refractory Chronic Graft-Versus-Host Disease

Initial Presentation

• A 58-year-old man previously underwent myeloablative conditioning and an allogeneic PBSC transplant for acute lymphocytic leukemia
• Received tacrolimus and methotrexate for GVHD prophylaxis
• At 10 months post-transplant, patient developed moderate muscle and joint pain with decreased range of motion, mild erythematous rash on cheeks

First-line Treatment

• Patient received topical steroid cream for rash, and was started on oral prednisone at 1 mg/kg/day
• After 4 weeks of treatment, the patient’s rash resolved but muscle/joint pain continued

Second-line Treatment

• Patient is now receiving ruxolitinib 10 mg orally twice daily, alongside 1 mg/kg/day steroids

Pashna Munshi, MD: The JAK-STAT pathway causes T-cell activation. Because ruxolitinib is a JAK inhibitor, it inhibits this T-cell expansion and the proliferation of cytokines. Overall, it improves the regulatory T-cell function and viability. When patients have already received steroids—the backbone of therapy for chronic or acute GVHD [graft-vs-host disease]—and they’re refractory or dependent on them, there’s persistent inflammation in their body. Targeting other pathways becomes of importance.

I can briefly talk about the study design and the pivotal trial that led to the approval of ruxolitinib. This was the REACH3 trial, an open-label phase 3 randomized trial for the efficacy and safety of ruxolitinib. It had a starting dosage of 10 mg twice a day, compared with investigators’ choice of best-available therapy of 10 commonly used treatments. It could be anything from ECP [extracorporeal photopheresis] to calcineurin inhibitors or methotrexate. The population was patients who were 12 years and older, and these patients all had moderate to severe steroid-refractory, steroid-dependent chronic GVHD. The primary end point of this trial was an overall response rate at week 24, and the key secondary end points were failure-free survival and an improved score on the modified Lee Symptom Scale at week 24.

A total of 329 patients underwent randomization. This study reached its primary end point, showing a 49.7% overall response rate with ruxolitinib compared with 26% with best-available therapy at week 24. Additionally, in the secondary end points, ruxolitinib was shown to have a longer median failure-free survival than those who had best-available therapy: more than 18 months vs about 5.7 months in the best-available-therapy arm.

These patients had a higher symptom response. Dr Stephanie Lee presented these data at the recent ASH [American Society of Hematology 2021 Annual Meeting], looking at the quality-of-life data using patient-reported outcomes on the REACH3 study. The authors used the modified Lee Symptom Scale, which is 1 of the main standards for assessing symptom burden and chronic GVHD. They looked at these results with objective organ responses with the data cut off in May 2020. They saw that patients who received ruxolitinib had higher responses on the modified Lee Symptom Scale at week 2, and that means ruxolitinib was able to make patients feel better compared with the standard therapies for chronic GVHD, even when they had steroid-refractory or steroid-dependent [disease]. That’s important because you want to get these patients off steroids quickly. If they have adverse effects, you want to make them feel better and have their pain and sensitivity symptomology improve.

Transcript edited for clarity.