Case Presentation: From Acute GVHD to Steroid Dependence

Dr. Shune discusses how objective clinical assessments guide both the timing of therapy changes and the selection of second-line treatment in cGVHD. She emphasizes the importance of standardized measurements, including body surface area involvement for skin disease, range-of-motion assessments for joint and fascial involvement, and pulmonary function tests, particularly forced expiratory volume in one second (FEV1), to evaluate lung involvement. These organ-specific measures are incorporated into the NIH consensus criteria to generate an overall severity score, which directly informs treatment decisions. Patients classified as having moderate to severe cGVHD by NIH criteria require systemic therapy, and worsening scores or inadequate response signal the need to escalate or modify treatment.

In patients who are steroid refractory or steroid dependent, as in the presented case, Dr. Shune outlines the current FDA-approved second-line systemic options. Ibrutinib, approved in 2017, targets the Bruton tyrosine kinase (BTK) pathway as well as inducible T-cell kinase, affecting both B-cell and T-cell signaling. Ruxolitinib, approved in 2021 based on the REACH3 clinical trial, inhibits the JAK1/JAK2–STAT signaling pathway and has demonstrated robust efficacy in cGVHD.

Although both agents are effective, Dr. Shune highlights that clinical phenotype plays a key role in agent selection. In patients with predominantly sclerotic manifestations involving the skin, joints, or lungs, ruxolitinib is often preferred because of its demonstrated activity in these disease features. In contrast, data supporting ibrutinib suggest greater benefit in patients with more inflammatory presentations, such as oral mucosal involvement, and its use may be limited by additional side effects. Based on these considerations, ruxolitinib has become her preferred second-line therapy for patients with moderate to severe cGVHD characterized by sclerotic disease.