Steroid-Refractory cGVHD: Risk Factors and Clinical Challenges

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

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

EP: 4.Treatment Options for Steroid-Refractory cGVHD

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: Typically, I counsel my patients that the risk of GVHD [graft-vs-host disease] following a transplant is a blanketed 50%, depending on the type of regimen they’ve received. Anywhere from 30% to 60% is the overall risk of GVHD. On top of that, there’s about a 40% to 50% risk of chronic GVHD, particularly at 1 year and 2 years early out from an allogeneic stem cell transplant. And the risk factors that put people at a higher risk of developing steroid-refractory GVHD are if they’ve had a few GVHD and recurrent flares that buy them a longer course of steroids, and then with each taper, there is another flare that potentially puts them at higher risk of chronic GVHD and steroid-refractory chronic GVHD. About 50% of these patients, it’ll be hard to taper them off completely of steroids, and oftentimes additional agents need to be added on. However, the mechanism of steroid resistance in chronic GVHD is not completely well-described, but there have been preclinical data to show that there are many chronic inflammatory pathways that are often involved, and there’s a lot of research that has gotten into this. We’re very excited that the field has now many new developments in what we can use in the clinical practice setting for chronic GVHD that’s steroid-refractory or dependent.

Typically, patients with chronic GVHD, unlike those with acute GVHD, do not have complete responses. In that, if somebody has acute GVHD and we treat them with a high dose of steroids, you expect that if they had diarrhea that the diarrhea completely goes away, and that’s called complete response, at 1 week of initiating steroids. With chronic GVHD, given that any kind of organ system can be involved all the way from the head to the feet, and it could be skin or the eyes, it could be a more protracted course, and it requires careful assessments at frequent intervals, particularly because the symptoms may come about more subtly, over the course of many months, and it takes many months to even see a response. In skin sclerosis and ocular symptoms, they take very long to stabilize and improve, while symptoms like oral pain and sensitivity are easier for clinicians and patients to score based on alleviation of these symptoms. And the patient will tell you they’re feeling better. These are some of the nuances and challenges in managing steroid-refractory chronic GVHD in the clinical setting.

Transcript edited for clarity.