A critical review of belumosudil in adult and pediatric patients with chronic graft-versus-host disease

Introduction Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is the main cause of late non-relapse mortality (NRM). Three new agents are now approved to treat cGVHD, of which belumosudil has a unique and dual mechanism of action of i) targeting the Rho-GTPase-associated coiled-coil kinase 2 (ROCK2) in T helper follicular cells (TFH) and TH17 cells, this results in downregulation of proinflammatory cytokines (interleukin −21 and 17), the former in a STAT3-dependent mechanism, ii) inhibition of tissue fibrosis by targeting stress-induced polymerization of G-actin fibrils by inhibiting the Rho-ROCK-MRTF pathway.Areas covered In this review we describe the epidemiology of cGVHD, its cardinal symptoms, preventive and therapeutic options, including second-line approved therapies in the United States (US). Clinical trial data that led to approval of belumosudil is discussed, in addition to the clinical scenarios in which the approved drugs may be most applicable.Expert opinion Belumosudil is approved for treatment of adult and pediatric patients ≥ 12 years with cGVHD after failing two lines of therapy based on results of the ROCKstar study that showed high overall response rates (ORR), favorable adverse effect profiles, and low rates of severe infections. With the availability of three new agents for treatment of cGVHD, treating physicians have more therapeutic options for patients and have additional options of development new clinical trials using a combination of recently approved drugs.