GvHD Connect
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8h
ROCK2 inhibition in steroid-refractory chronic GvHD: real-world outcomes, risk stratification, and corticosteroid-sparing evidence

Chronic graft-versus-host disease (cGvHD) is a leading cause of late morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation. Steroid-refractory cGvHD carries poor prognosis, demanding effective targeted salvage strategies.

A selective ROCK2 inhibitor with immunomodulatory and antifibrotic properties demonstrated durable efficacy in a multicenter Canadian real-world study of 46 heavily pretreated steroid-refractory cGvHD patients: best overall response rate 52%, 12-month failure-free and overall survival 64.3% and 91.1%, respectively. Corticosteroid discontinuation was achieved in 73% by 12 months. A prognostic risk model stratifying by prior acute GvHD and organ involvement (≥4 organs) identified distinct 12-month failure-free survival rates of 100%, 75.8%, and 30% for zero, one, and two risk factors (HR 3.91; p=0.003), informing patient selection and therapeutic sequencing.

Hematologists, transplant physicians, and immunologists managing steroid-refractory cGvHD will benefit from peer discussion of ROCK2 inhibitor evidence, risk-stratified patient selection, combination therapy, and corticosteroid-sparing strategies.

How do you use organ involvement, prior acute GvHD history, and prior JAK inhibitor exposure to guide patient selection and sequencing when initiating ROCK2 inhibitor therapy in steroid-refractory cGvHD? What clinical response milestones guide your decisions to continue, adjust, or discontinue targeted therapy in steroid-refractory cGvHD, and how do you approach non-responders?

  • 8h
    In steroid refractory patients, tend to use ROCK2 but challenge due to authorization restrictions and usually first utilizing Ruxolitinib as well as ibrutnib and axatilimab. Choice based on multiple factors Show More
  • 1w
    Belumosudil is a ROCK2 inhibitor FDA-approved for cGvHD after failure of at least two prior lines of systemic therapy, so its formal positioning is third-line or later. It is a Show More

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Did you know?

Steroid-refractory acute graft-versus-host disease (aGVHD) carries a mortality exceeding 50%, and no standard second-line therapy had been established until recently. The REACH2 Phase 3 trial (n=309 patients with steroid-refractory grade II–IV aGVHD) demonstrated that JAK1/2 inhibition achieved an overall response rate of 62% at Day 28 vs. 39% with best available therapy (OR 2.64; p<0.001), with significantly higher rates of durable response at Day 56 and meaningful reductions in non-relapse mortality.

NCCN Guidelines
Discussion question

How has the REACH2 data changed your institutional approach to second-line management of steroid-refractory acute GVHD — and how are you monitoring for and managing the most clinically significant adverse events with JAK inhibition in this setting?

  • 8h
    Still remains as a second-line management for steroid refractory situations. Still need to watch for toxicity as well as serologic monitoring for transaminases and blood cell count changes
  • Yesterday
    REACH2 has made ruxolitinib my preferred second-line option for steroid-refractory acute GVHD when appropriate. I monitor closely for cytopenias, infections, and viral reactivation, particularly CMV, as well as liver abnormalities. Show More

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Early-Onset Hemophagocytic Lymphohistiocytosis and Inflammatory Neurotoxicity Prior to Post-transplant Cyclophosphamide: A Report of Two Cases. - PubMed

Early-Onset Hemophagocytic Lymphohistiocytosis and Inflammatory Neurotoxicity Prior to Post-transplant Cyclophosphamide: A Report of Two Cases. - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/42598691

Explore two cases of early hyperinflammatory toxicities post-transplant, highlighting diagnostic challenges and rapid response to emapalumab and tocilizumab in mismatched transplants.


Two cases highlight early hyperinflammatory toxicities post-transplant, including severe cytokine release syndrome and neurotoxicity. Rapid improvement with emapalumab and tocilizumab noted.

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Living Donor Liver Transplantation as Salvage Therapy for Steroid-Refractory Chronic Hepatic GVHD Following Allogeneic Hematopoietic Stem Cell Transplantation. - PubMed

Living Donor Liver Transplantation as Salvage Therapy for Steroid-Refractory Chronic Hepatic GVHD Following Allogeneic Hematopoietic Stem Cell Transplantation. - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/42531434

Explore a pediatric oncology case where living donor liver transplantation treated steroid-refractory chronic hepatic GVHD after multiple therapies, highlighting the importance of multidisciplinary planning.


Living donor liver transplantation offers a viable option in pediatric oncology patients with steroid-refractory chronic hepatic GVHD after multiple therapies fail. Multidisciplinary planning is crucial.

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2w
Immune reconstitution and viral reactivation after allogeneic hematopoietic stem cell transplantation in hematologic malignancies. - PubMed

Immune reconstitution and viral reactivation after allogeneic hematopoietic stem cell transplantation in hematologic malignancies. - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/42535760

Discover how post-transplant immune reconstitution affects viral reactivation in hematologic malignancies and its limited impact on survival.


Higher bone marrow B-cell proportion at six months significantly reduces CMV reactivation odds. Viral reactivation not significantly impacting survival.