New Combination Therapy Offers Hope for Severe Chronic Graft-Versus-Host Disease
A groundbreaking study has revealed that combining axatilimab-csfr (Niktimvo) with ruxolitinib (Jakafi) and/or belumosudil (Rezurock) shows promising results for patients with severe chronic graft-versus-host disease (cGVHD). This single-center, retrospective study, presented at the 2025 Tandem Meeting, highlights the potential of triple therapy in treating highly refractory cases.
Key Findings of the Study
The study involved eight heavily pretreated patients who received various combinations of the drugs. The overall response rate (ORR) according to National Institutes of Health (NIH) Consensus Criteria was 25%, while 75% showed Clinically Significant Symptomatic Improvement (CSSI). These figures emphasize the significant impact of combination therapy in severe cGVHD cases.
“This research marks the first time axatilimab has been used in combination with ruxolitinib and/or belumosudil,” commented Jean Caputo, APRN-CNP, from the division of hematology at The Ohio State University. “The results indicate that this combination can be both feasible and tolerable, offering clinical benefits in highly refractory cGVHD.”
Background on the Treatments
Axatilimab, a CSF-1R-blocking antibody, is the latest FDA-approved treatment for cGVHD following at least two prior lines of systemic therapy. Its approval was based on the phase 3 AGAVE-201 trial, which did not permit combination therapy with other cGVHD treatments like ruxolitinib and belumosudil.
Caputo highlighted that the NIH Consensus Criteria grades disease severity based on organ involvement and symptom severity, while CSSI is a provider-assessed measure that also incorporates patient-reported symptoms, providing a comprehensive assessment of cGVHD in severe and refractory cases.
Treatment Details and Responses
All study participants had received multiple prior therapies, including ruxolitinib and belumosudil, sometimes in combination. When axatilimab was introduced, it was combined with both ruxolitinib and belumosudil in four patients, with belumosudil alone in three, and with ruxolitinib in one.
Among six CSSI partial responders, four were treated with axatilimab, ruxolitinib, and belumosudil; one with axatilimab and ruxolitinib; and one with axatilimab and belumosudil. No complete responses were recorded, but five patients achieved stable disease, and one experienced disease progression.
Duration and Impact of Responses
The median time to response was 71 days, with a median duration of response of 295 days by NIH criteria and 219 days by CSSI criteria. However, three patients initially responding by CSSI later experienced disease progression and discontinued axatilimab.
For organ-specific responses, the ORR was 15% by NIH and 43% by CSSI for skin GVHD; 25% by NIH and 75% by CSSI for oral involvement; 50% by CSSI for lung involvement; and 20% by CSSI for musculoskeletal involvement.
“Partial responses included improvements in scleroderma, mouth ulcers, joint mobility, and reduced breathing difficulties,” Caputo noted.
Cytokine Levels and Adverse Events
Levels of inflammatory cytokines such as interleukin-6, interleukin-2R, and interleukin-10 were decreased in CSSI responders. One patient with disease progression had elevated levels of these cytokines.
No patient discontinued axatilimab due to intolerance, and no fatal adverse events were reported. The most common side effects were anemia (grade 1 to 3) and viral upper respiratory tract infections (grade 2 to 3). One patient experienced serious adverse events, including septic arthritis, osteomyelitis, and elevated gamma-glutamyl transferase.
Implications of the Study
While the ORR was lower than the 74% found in the AGAVE-201 trial, Caputo noted that the current study group had more severe disease, with half already refractory to combination ruxolitinib and belumosudil.
This study signifies a significant step forward in managing cGVHD, particularly for patients who have failed multiple lines of treatment. It opens avenues for further research and potential clinical applications of combined therapy approaches.
Conclusion
The findings presented at the 2025 Tandem Meeting underscore the potential of combining axatilimab-csfr with ruxolitinib and belumosudil in treating severe, chronic graft-versus-host disease. This combination therapy shows promise in providing meaningful clinical benefits and quality of life improvements for patients with refractory cGVHD.
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