Assessing the value contribution of belumosudil in the treatment of chronic graft-versus-host disease (CGVHD) after the failure of at least two previous lines of systemic therapy through multi-criteria decision analysis

Abstract

Background: Chronic graft-versus-host disease (cGVHD) is a rare and serious complication following allogeneic hematopoietic cell transplantation and a major cause of long-term morbidity and mortality. Approximately half of transplant recipients develop cGVHD, and therapeutic options are particularly limited for patients who fail at least two lines of systemic therapy. In this setting, no treatments are approved in the European Union. Belumosudil, an oral selective ROCK2 inhibitor, is currently under evaluation by the European Medicines Agency (EMA) for this indication. Objective: To evaluate the value contribution of belumosudil for the treatment of cGVHD after failure of two or more systemic therapies, using a Multi-Criteria Decision Analysis (MCDA) approach adapted for orphan drugs in the Spanish healthcare context. Methods: An MCDA was conducted using the EVIDEM framework adapted for orphan drug assessment. A multidisciplinary panel of hematologists, hospital pharmacists, healthcare managers, and a patient representative evaluated 13 quantitative and contextual criteria. Evidence was compiled through a structured literature review and presented in an evidence matrix. Each expert scored the matrix independently and participated in a reflective discussion to contextualize and reassess their evaluations. Results were analysed to determine mean scores, variability, and value contribution. Results: Belumosudil achieved a high overall MCDA score (0.65). The main contributing criteria were disease severity, unmet needs, therapeutic impact, and comparative efficacy. Experts highlighted its favourable clinical profile, symptom control potential, and relevance in a patient population lacking approved alternatives. Contextual criteria also received positive assessments, indicating alignment with health system priorities and feasibility of implementation. Reflective discussion reduced variability and strengthened the consensus on its value. Conclusions: Belumosudil represents a valuable treatment option for patients with advanced cGVHD, a population with significant unmet needs. The use of reflective MCDA enabled a comprehensive and transparent value assessment, integrating clinical, economic, and contextual dimensions. These findings may support value-based decision-making for the adoption of orphan drugs within healthcare systems