Sequencing Strategies and the Role of Combination Therapy

EP: 1.Early Challenges in the cGVHD Journey

EP: 2.Navigating the Path to Second-Line Therapy

EP: 3.Steroid-Refractory cGVHD: A Look at FDA-Approved Options

EP: 4.Emerging Data: Impacts of ROCKstar and AGAVE-201

EP: 5.Tailoring Therapy: Weighing Evidence, Organ Involvement, and Route of Administration

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EP: 6.Sequencing Strategies and the Role of Combination Therapy

At Emory Healthcare, the treatment pathways for chronic graft-vs-host disease (cGVHD) are evolving, with a shift toward incorporating emerging therapies as the data on durable outcomes becomes more robust. Although there isn't a formal algorithm in place, clinicians have adapted their practices based on real-world data, often introducing therapies like belumosudil earlier in the treatment sequence, sometimes even in the second line of therapy. The key challenge in this space is understanding how to optimally sequence treatments, as patients with severe chronic GVHD often present with significant organ damage and fibrotic changes, which can complicate their response to new therapies. As more data becomes available, including biomarkers and inflammatory markers, treatment selection will become increasingly personalized.

Off-label combination therapies are a prominent area of interest, especially in cases where patients are refractory to first and second-line treatments. Clinicians have started using combinations of drugs, such as combining Rexona [NL1] and belimumab, to achieve better responses, particularly in steroid-sparing regimens. These combinations are particularly beneficial in reducing the long-term reliance on steroids, which carry significant toxicity risks. However, this approach remains in a gray zone, as much of the evidence is based on small, retrospective studies rather than large-scale clinical trials. Despite this, the real-world data shows that combination therapies can help improve patient outcomes and provide more effective management of chronic GVHD.

The decision to add or change therapy in nonresponsive patients depends largely on their response to initial treatments. If a patient has been on a drug for about 2 months with minimal organ response but has been able to taper off steroids, adding another drug may be an option to enhance efficacy. On the other hand, if a patient is intolerant to a therapy, such as experiencing severe infections or significant adverse effects, a change in the treatment approach is necessary. Ultimately, treatment decisions are made based on a patient-centric approach, considering both the patient's specific disease manifestations and their ability to tolerate therapies