What are the treatment options for ruxolitinib-refractory acute GvHD?

The GvHD Hub was pleased to speak with Mohamad Mohty. We asked, What are the treatment options for ruxolitinib-refractory acute GvHD?

In this interview, Mohamad Mohty discusses the evolving management of steroid-refractory acute GvHD, highlighting ruxolitinib as the standard of care and the importance of robust supportive measures. Mohty explores treatment options for ruxolitinib-refractory disease – including extracorporeal photopheresis, mesenchymal stromal cells, and emerging targeted approaches. Mohty highlights the value of referral to specialized centers and clinical trial enrolment as treatment shifts toward precision-guided, biology-driven strategies.

Key learnings

• Acute GvHD that progresses after 3–5 days or does not improve after 5–7 days of corticosteroid initiation – and after exclusion of infections, drug toxicity, or primary disease flare – is considered steroid-refractory acute GvHD (SR-aGvHD).^1,2
• Ruxolitinib is the current standard of care for first-line treatment in the steroid-refractory setting.
  • In the phase III REACH2 trial (NCT02913261), ruxolitinib demonstrated a Day 28 best overall response rate of 82%, compared with 61% in the control group (investigator’s choice of therapy).¹
• Supportive care, including infection prophylaxis, cytomegalovirus monitoring, nutritional support, mucosal and skin care, and close management of fluid balance, is essential for patients in this setting.
• For patients who do not respond to ruxolitinib treatment – termed “ruxolitinib-refractory” – there are several therapeutic options.
• Extracorporeal photopheresis (ECP) can be considered mainly for patients with cytopenia that limit other systemic therapies and those with skin-predominant GvHD.
• Mesenchymal stromal cells (MSCs) have proven to be an important treatment option and have shown particular benefit in pediatric patients with SR-aGvHD.
  • MSC-Frankfurt am Mein (MSC-FFM), an MSC preparation produced from bone marrow-derived mononuclear cells of eight donors, has demonstrated efficacy and a well-tolerated safety profile across multiple real-world cohorts of patients with refractory acute GvHD.^3–6
  • The ongoing phase II BALDER (NCT06075706) and phase III IDUNN (NCT04629833) trials are investigating MSC-FFM compared with best available therapy in pediatric and adult patients with SR-aGvHD.
• Emerging targeted approaches include JAK inhibitors beyond ruxolitinib, α4β7 blockade, and fecal microbiota transplantation (FMT).
  • FMT has shown efficacy in clinical trials, including MaaT013, which is a full-ecosystem microbiota therapy.
• Referral to specialized centers and clinical trial enrolment is encouraged, given the complexity of the disease and the evolving treatment landscape.
• Overall, the management of refractory acute GvHD has shifted from broad immunosuppression to precision-guided, biology-driven therapy that optimizes disease control and infection prevention. Early identification, rapid initiation of treatment, and meticulous supportive care remain important.

This educational resource is independently supported by Medac. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.