The rho-related coiled-coil protein kinase 2 (ROCK2) signaling pathway regulates the Th17/regulatory T cell balance and controls the fibrotic pathway.
The selective inhibition of ROCK2 with belumosudil (KD025) may provide a new method for the treatment of chronic graft-versus-host disease (cGVHD).
A Phase IIa, open-label dose exploratory study " ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease " published in the " Journal of Clinical Oncology " recently , aimed at clarifying Beludi The dose and effect of ER for cGVHD patients who have previously received first-line third-line therapy (LOT).
The primary endpoint is the overall response rate (ORR).
A total of 54 cGVHD patients were recruited, and the median time from diagnosis of cGVHD to enrollment was 20 months.
78% of patients had severe cGVHD, 50% of patients involved at least 4 organs, 73% of patients had last LOT refractory cGVHD, and 50% of patients had received at least third-line treatment in the past.
Remission rate of different groupsRemission rate of different groups
With a median follow-up of 29 months, the ORR (95% CI) of berudil at doses of 200 mg·1/day, 200 mg·2/day, and 400 mg·1/day were 65% (38%- 86%), 69% (41%-89%) and 62% (38%-82%) .
Duration of remission of berudil treatmentDuration of remission of berudil treatment
The remission rate is clinically significant, with a median duration of remission of 35 weeks, and is associated with improved quality of life and reduced corticosteroid (CS) consumption.
CS treatment was discontinued in 19% of patients.
The failure-free survival rates at 6 months and 12 months were 76% (62%-85%) and 47% (33%-60%), respectively.
The 2-year overall survival rate was 82% (69%-90%).
Remission rate of different organsRemission rate of different organs
Beludil is well tolerated and the incidence of cytopenias is low.
Unexpected adverse reactions did not occur, and the risk of infection (including cytomegalovirus infection and reactivation) did not increase significantly.
In short, berudil treatment can enable patients to obtain high ORR and overall survival rate, and at the same time can improve the quality of life of patients, reduce CS dose and limit toxicity .
The results of this study suggest that berudil may be an effective choice for patients with refractory cGVHD.
Original source:Original source:
Madan Jagasia, et al.
0/" target="_blank" rel="noopener">ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease .
J Clin Oncol.
0/" target="_blank" rel="noopener">ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease
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