MSC treatment for patients with SR-aGvHD: Long-term results from a phase III trial

Around 80% of patients with chronic graft-versus-host disease (cGvHD) have a history of acute GvHD (aGvHD), and tend to have worse outcomes compared with de novo cGVHD, making modulating aGvHD development and preventing its evolution to cGvHD an important therapeutic objective.¹ Initial results from an open-label, multicenter, randomized phase III trial (NCT02241018) of mesenchymal stromal cells (MSCs), an aGvHD prophylactic and treatment, plus aGvHD therapy in patients with steroid-resistant aGvHD (SR-aGvHD) across nine centers in China (N = 198) found a reduction in the incidence and severity of cGvHD.

The 5-year follow-up from this trial (n = 185; MSC group, n = 101; control group, n = 84) and a post-hoc analysis of the underlying mechanism of MSCs were published in Experimental Hematology & Oncology by Zhao, et al.¹

Key learnings

Patients in the MSC group had a reduced cumulative incidence of cGvHD (42.0% vs 67.1%; HR, 2.19; 95% CI, 1.47–3.27; p < 0.001) and severe cGvHD (11.0% vs 27.4%; HR, 2.85; 95% CI, 1.40–5.80; p = 0.003) compared with the control group.

MSC treatment improved 5-year OS (60.4% vs 41.7%; HR, 0.63; 95% CI, 0.42–0.94; p = 0.023) and CRFS (33.9% vs 20.9%; HR, 0.67; 95% CI, 0.48–0.93; p = 0.017) compared with results seen in the control group.

Exploratory analysis showed increased levels of Tregs, CD4⁺CD45RA⁺CD31⁺ naïve T-cells, and sjTRECs in the peripheral blood with MSCs vs control, confirming MSCs decrease the incidence and severity of cGvHD through the thymus pathway.

These findings support MSCs as a viable treatment option for patients with SR-aGvHD, aiming to reduce the cGvHD burden and improve long-term survival outcomes.