Chronic graft-vs-host disease (cGVHD) treatment is undergoing significant evolution as clinicians and researchers work to address persistent challenges in patient outcomes. Current steroid response rates remain at approximately 50%, highlighting the urgent need for improved therapeutic approaches and combination strategies.
Emerging Treatment Sequencing Strategies
At Emory Healthcare, treatment pathways for chronic GVHD are evolving with a shift toward incorporating emerging therapies as data on durable outcomes becomes more robust. 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.
Combination Therapy Approaches
Off-label combination therapies have emerged as 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 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, real-world data shows that combination therapies can help improve patient outcomes and provide more effective management of chronic GVHD.
Treatment Decision-Making Framework
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. Conversely, 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.
Future Research Priorities
The possibility of adding drugs alongside steroids in the initial treatment regimen was discussed, though past attempts have been unsuccessful. There is hope that newer drugs might improve response rates when introduced early in the treatment process. Additionally, combination therapies, though mostly explored in retrospective studies, may hold promise. Larger, prospective trials are needed to better understand which drug combinations work best for managing chronic GVHD.
Biomarker-Guided Therapy Revolution
An exciting area of future research is the identification and application of biomarkers to predict treatment responses. The ability to tailor therapies based on biomarkers could revolutionize treatment protocols and help personalize care for patients. Currently, treatments are largely guided by generalized algorithms, but the use of biomarkers would allow for more precise treatment choices, improving patient outcomes.
Steroid-Free Treatment Development
Researchers and clinicians are eager to find therapies that could reduce or eliminate the need for steroids in the initial treatment phase. While steroids are effective in managing symptoms, their long-term adverse effects—such as cardiovascular complications, osteoporosis, and diabetes—pose significant challenges for patients.
Additionally, earlier intervention and better prophylaxis regimens could help prevent chronic GVHD altogether. These efforts align with ongoing research into real-world outcomes and the evolving role of prophylactic treatments in improving long-term patient health and quality of life.
