Real-world outcomes of belumosudil compared with best available therapy: Results from the ROCKreal study

Belumosudil is a selective inhibitor of Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), a signaling protein involved in inflammation and fibrosis.¹ It is approved in the US for the treatment of chronic graft-versus-host disease (cGvHD) after failure of at least two prior lines of systemic therapy.¹

The phase II ROCKstar trial (NCT03640481) evaluated belumosudil 200 mg once or twice daily in 132 patients with heavily pre-treated cGvHD; safety and efficacy were assessed for up to 3 years.¹ The study found that daily treatment with 200 mg of belumosudil induced responses in 74% of patients, including those with cGvVHD refractory to steroids, ruxolitinib, and ibrutinib.¹ However, these positive results only apply to a specific patient population, with strict inclusion and exclusion criteria, and therefore additional real-world data are needed to complement the findings, particularly comparison with current best available therapy (BAT).

ROCKreal study design²

ROCKreal was a non-interventional, chart-review study across eight centers in the US, which imitated a phase III trial through causal inference methodology. Patients aged ≥12 years with cGvHD who had received 2–5 prior lines of therapy between 2015–2024 were included in the study; those previously exposed to belumosudil were excluded. 

Adjusted overall response rate (ORR) at 6 months was used to assess patient response; a responder was classified as a patient with a complete or partial response, or a 50% reduction in corticosteroids without disease progression. Response failure was defined as mixed response, disease progression, relapse, treatment switching, or death. 

Efficacy and safety results 

In total, 196 patients were included in the study, of which 113 received belumosudil and 83 BAT, resulting in 358 LOTs (113 belumosudil, 245 BAT). There was a higher median age and number of prior LOTs at baseline in the belumosudil group compared with the BAT group (Table 1).

Table 1. Baseline characteristics for patients in the ROCKreal study*

Efficacy

More patients treated with belumosudil achieved the primary endpoint of overall response at 6 months (Figure 2) compared with those who received BAT (38.7% vs 26.8%; p = 0.040).

Safety

In total, adverse events (AEs) were experienced across 27% of the belumosudil LOTs, and 36% of BAT LOTs (Table 2). The incidence of severe AEs was higher with belumosudil LOTs (58%) than for BAT LOTs (46%). 

Table 2. Incidence of AEs, including severity and type, in the ROCKreal study*

Conclusion

In the ROCKreal study, belumosudil showed superior efficacy compared with best available therapy, even in later LOTs. These Rresults from the ROCKreal study are consistent with those from the ROCKstar trial, providing further evidence for the safety and efficacy of belumosudil in patients with refractory cGvHD. Limitations of the study include the potential for AEs to be under-reported, and also adherence to fixed monitoring schedules could also have been lacking; therefore, further real-world studies are warranted. 

This educational resource is independently supported by Sanofi. All content was developed by SES in collaboration with an expert steering committee; funders were allowed no influence on the content of this resource.