Both the prevention and the treatment of graft-versus-host disease (GVHD) have advanced meaningfully, giving transplant physicians better tools at each stage.
Prevention
The standout prevention advance is post-transplant cyclophosphamide (PTCy)-based prophylaxis. In a Phase 3 trial, the combination of PTCy, tacrolimus, and mycophenolate mofetil improved one-year GVHD-free, relapse-free survival (about 53% vs 35%) compared with the long-standing tacrolimus-plus-methotrexate regimen, without compromising overall or disease-free survival. PTCy-based prophylaxis has consequently been widely adopted, including for well-matched donors.
Treatment of steroid-refractory disease
Corticosteroids remain first-line, but options for refractory disease have expanded. Ruxolitinib, a JAK1/2 inhibitor, is approved for both steroid-refractory acute GVHD (REACH2) and chronic GVHD (REACH3), where it roughly doubled response rates and extended failure-free survival. For chronic GVHD specifically, two further mechanisms are now available: belumosudil, a ROCK2 inhibitor (approved 2021), and axatilimab (Niktimvo), a first-in-class anti-CSF-1R antibody approved in August 2024 on the strength of the AGAVE-201 trial (a 75% response rate after at least two prior lines). Axatilimab is notable for targeting the monocyte- and macrophage-driven fibrosis that characterizes chronic GVHD — a distinct mechanism from the immunosuppressants used earlier in the course.
Further reading: PTCy-based prophylaxis (Bolaños-Meade et al., NEJM 2023); ruxolitinib REACH3 (Zeiser et al., NEJM 2021); axatilimab AGAVE-201 (Wolff et al., NEJM 2024).