Translating Innovation Into Practice: Emerging Treatments and Real-World Data in GVHD - Episode 7
Insights Into Real-World Evidence in Chronic GVHD
Panelists discuss how real-world evidence shows lower response rates and shorter time to next treatment compared to clinical trials due to more advanced patient populations and different monitoring practices, while highlighting the potential value of combination therapies using multiple FDA-approved agents simultaneously despite the lack of formal trial data supporting such approaches.
Insights Into Real-World Evidence in Chronic GVHD
This segment discusses the emerging real-world evidence for chronic graft-vs-host disease (GVHD) therapies, acknowledging that real-world response rates typically fall below clinical trial results due to factors including more advanced patient populations, medication compliance issues, and less rigorous response assessment. Two key abstracts from the recent EBMT conference in Florence, Italy, provided insights into belumosudil usage patterns from publicly available databases. The data revealed that most patients receiving belumosudil had previously failed ruxolitinib, which has become the preferred first-line salvage therapy after steroids based on the strong REACH-3 trial data and physician comfort with the agent. Time to next treatment was considerably shorter in real-world practice (4.5 months) compared to clinical trials (16-26 months in the ROCKstar trial), likely reflecting clinicians' willingness to add or switch therapies more quickly when optimal responses aren't achieved.
Similar real-world data for axatilimab demonstrated responses even in heavily pretreated patients, with approximately 50% having multiorgan involvement and exposure to multiple prior treatment lines. This supports the clinical utility of axatilimab in advanced, refractory cases. Institutional data from posttransplant cyclophosphamide protocols shows promising trends, with sclerodermatous chronic GVHD incidence falling below 10%, suggesting that improved prevention strategies may be changing disease presentation patterns and reducing severe fibrotic manifestations. This represents encouraging progress for patient outcomes as preventive approaches continue to evolve.
The discussion highlights a significant gap in clinical trial design - the lack of combination therapy studies despite widespread real-world use of multiple agents simultaneously. Many clinicians combine ruxolitinib, belumosudil, and axatilimab when partial responses from single agents are insufficient for patient quality of life. This practice is considered safe given the distinct mechanisms of action (JAK inhibition, ROCK2 inhibition, and CSF-1R blockade), and clinicians attempt dose reductions while maintaining efficacy. The emerging real-world evidence on combination therapies represents a critical area for future research, as these approaches may provide superior responses compared to sequential monotherapy. Such data will be essential for optimizing treatment strategies and potentially improving complete response rates in this challenging patient population.
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