Belumosudil for Chronic Graft-Versus-Host Disease: A Systematic Review and Meta-Analysis

Chronic graft-versus-host disease (cGvHD) is a debilitating complication following allogeneic hematopoietic stem cell transplantation, often refractory to standard therapies. Belumosudil, a selective ROCK2 inhibitor with immunomodulatory and antifibrotic properties, has emerged as a targeted treatment option, gaining FDA approval for third-line therapy in 2021. However, its clinical efficacy and safety across diverse patient populations remain incompletely characterized.

We conducted a systematic review and meta-analysis of 16 studies encompassing 651 adult patients with cGvHD treated with belumosudil. Both prospective and retrospective studies reporting on overall response rate (ORR), organ-specific response, survival outcomes, and adverse events were included. Bayesian random-effects models were used to estimate pooled outcomes and assess heterogeneity. Meta-regression evaluated the impact of prior ruxolitinib exposure, disease severity, and lung involvement on treatment response.

The pooled ORR was 60% (95% CI, 53 to 67), highest in prospective studies (73%) and lowest in retrospective multicenter cohorts (54%). Organ-specific responses were most favorable in gastrointestinal (52%) and joint/fascia (52%) involvement, but notably poor in lung cGvHD (25%). Prior ruxolitinib exposure was associated with lower ORR, while concurrent use and disease severity were not. The pooled overall survival was 87%, and failure-free survival was 57%. Adverse events were common but generally manageable; serious drug-related events occurred in ≤13% of patients, with Grade ≥3 pneumonia/lung infections in up to 17%.

Belumosudil demonstrates promising efficacy and a favorable safety profile in refractory cGvHD. Our findings support further investigation in earlier treatment and disease course.