(352) Transportability to the EU Population of the Efficacy of Belumosudil Versus Best Available Therapy for the Treatment of Chronic Graft-Versus-Host Disease

Background: : Belumosudil (BEL) is approved for the treatment of relapsed/refractory chronic graft-versus-host disease (cGVHD) after failure of 2 prior lines of therapy (LOTs) in the United States (US).

Objective: : Assuming similar biological responses across Europe (EU) and the US, a transportability analysis was conducted to model BEL treatment effects in EU patients with cGVHD based on observed effects in the real-world US population.

Methods: : Clinical and demographic data on US and EU patients aged ≥12 years with a cGVHD diagnosis were collected from visits to 8 US and 32 EU sites between March 1, 2015 and March 27, 2024. Inclusion criteria were cGVHD treated with 2–5 prior LOTs and the absence of disease relapse. Data elements—age, stem cell source, sex, prior LOTs, organ involvement, and comorbidities—were recorded at initiation of each LOT. Overall responses at 6 months after BEL treatment or best available therapy (BAT) for LOTs 3–6 were collected in the US only for each qualifying LOT, with LOT definitions standardized across sites. Using targeted maximum likelihood estimation, a rigorous methodology for causal inference with observational data, a targeted outcome regression model trained on US data was developed. Using this model and baseline data of EU patients with cGVHD, treatment-specific outcomes were predicted for EU patients treated with BEL or BAT. The treatment effect of interest was defined as the ratio of the proportion of responses or overall response rate (ORR) at 6 months post LOT initiation when treated with BEL vs BAT.

Results: : A total of 196 US patients and 222 EU patients were included, contributing 358 (113 BEL, 245 BAT) and 363 (363 BAT) LOTs, respectively. Most baseline characteristics, including sex, conditioning regimen, and history of Grade II–IV acute GVHD, were well balanced between the US and EU populations, while median age (52.6 vs 57.6 years) and rate of severe cGVHD (40% vs 51%) at initiation of LOTs 3–6 were lower in EU than in US. After adjusting for EU patient characteristics, the estimated 6-month ORR for EU patients with cGVHD when treated with BEL and BAT were 37.6% and 26.3%, respectively, presenting a 6-month ORR ratio of 1.43 (95% confidence interval: 1.05, ∞; p=0.03).

Conclusions: : The US and EU patients who failed 2–5 prior LOTs were broadly similar in terms of baseline characteristics. Similar to the positive effect observed in the US, findings from this transportability analysis indicate that BEL treatment would benefit EU patients with cGVHD, with an estimated 43% improvement in responses with BEL than with BAT.

Sponsorship:: Sanofi