ROCK2 inhibition with belumosudil (KD025) for the treatment of chronic graft-versus-host disease

Madan Jagasia, Aleksandr Lazaryan, Carlos R. Bachier, Amandeep Salhotra, Daniel J. Weisdorf, Behyar Zoghi, James Essell, Laurie Green, Olivier Schueller, Jeegar Patel, Alexandra Zanin-Zhorov, Jonathan M. Weiss, Zhongming Yang, David Eiznhamer, Sanjay K. Aggarwal, Bruce R. Blazar, Stephanie J. Lee

Resultado de la investigación: Articlerevisión exhaustiva

49 Citas (Scopus)

Resumen

PURPOSE The rho-associated coiled-coil-containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil (KD025) may offer a novel approach to the management of chronic graft-versus-host disease (cGVHD). PATIENTS AND METHODS A phase IIa, open-label, dose-finding study of belumosudil enrolled 54 patients with cGVHD who had received one to three prior lines of therapy (LOTs). The primary end point was overall response rate (ORR). RESULTS The median time from cGVHD diagnosis to enrollment was 20 months. Seventy-eight percent of patients had severe cGVHD, 50% had $ 4 organs involved, 73% had cGVHD refractory to their last LOT, and 50% had received $ 3 prior LOTs. With an overall median follow-up of 29 months, the ORR (95% CI) with belumosudil 200 mg once daily, 200 mg twice daily, and 400 mg once daily was 65% (38% to 86%), 69% (41% to 89%), and 62% (38% to 82%), respectively. Responses were clinically meaningful, with a median duration of response of 35 weeks, and were associated with quality-of-life improvements and corticosteroid (CS) dose reductions. CS treatment was discontinued in 19% of patients. The failure-free survival rate was 76% (62% to 85%) and 47% (33% to 60%) at 6 and 12 months, respectively. The 2-year overall survival rate was 82% (69% to 90%). Belumosudil was well-tolerated, with low rates of cytopenia. There were no unexpected adverse events and no apparent increased risk of infection, including cytomegalovirus infection and reactivation. CONCLUSION Belumosudil treatment resulted in a high ORR and overall survival rate and demonstrated quality-of-life improvements, CS dose reductions, and limited toxicity. Data from the study indicated that belumosudil may prove to be an effective therapy for patients with treatment-refractory cGVHD.

Idioma originalEnglish (US)
Páginas (desde-hasta)1888-1898
Número de páginas11
PublicaciónJournal of Clinical Oncology
Volumen39
N.º17
DOI
EstadoPublished - jun. 10 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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