What question did this study set out to answer?

This trial aims to evaluate the efficacy and safety of hUC-MSC PLEB001 combined with anti-CD25 antibodies for treating steroid-refractory GI graft-versus-host disease.

March 26, 2026Open Access

Mesenchymal stromal cells as add-on therapy to anti-CD25 antibodies for treating gastrointestinal-involved steroid-refractory acute graft-versus-host disease: a multicenter, single-arm, pivotal clinical trial

Key Points

This trial aims to evaluate the efficacy and safety of hUC-MSC PLEB001 combined with anti-CD25 antibodies for treating steroid-refractory GI graft-versus-host disease.
Conducted as a multicenter, single-arm, pivotal clinical trial
Patients with grade II or higher SR-GI-aGVHD received hUC-MSC PLEB001 plus anti-CD25 therapy
Infusions were done at a dose of 106 cell/kg twice weekly for 4 weeks
Efficacy was assessed primarily at day 28 based on overall response rates.
The overall response rate at day 28 was 63.0%
The complete response rate was 55.6%
At day 56, the overall response rate was 51.9%
The overall survival rates at days 28, 56, 100, and 360 remained high, with 94.4%, 88.9%, 79.6%, and 65.8% respectively
No serious adverse events were reported, indicating a well-tolerated treatment regimen.

Abstract

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) is the predominant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with gastrointestinal involvement (SR-GI-aGVHD) remaining a key obstacle. We conducted a multicenter, single-arm, pivotal trial to assess the efficacy and safety of hUC-MSC PLEB001, a human umbilical cord-derived mesenchymal stromal cells (MSCs) product, plus anti-CD25 monoclonal antibody as second-line therapy for SR-GI-aGVHD. Eligible patients with grade II or higher SR-GI-aGVHD received hUC-MSC PLEB001 with protocol-defined anti-CD25 monoclonal antibody therapy. hUC-MSC PLEB001 was infused at a dose of 106 cell/kg twice weekly for 4 consecutive weeks, starting at day 1, and efficacy was assessed on day 28. Patients achieving complete response (CR), progressive disease (PD) or no response (NR) concluded treatment; those with partial response (PR) continued the same regimen for additional 4 weeks. The primary endpoint of the study is the overall response rate (ORR) at day 28. Fifty-four patients (median age 43, range 14–68) were enrolled. The number of Grade II–IV SR-aGVHD patients was 21, 16, 17, respectively. Thirty-seven patients were GI-involved only, 15 patients were GI and skin involved, and 2 patients were GI and liver involved. The ORR at day 28 was 63.0% (95% CI 48.7%, 75.7%), with a CR rate of 55.6% (41.4%, 69.1%). The 28-day durable complete response rate (DCR) was 51.9% (37.8%, 65.7%). The ORR and CR rate at day 56 was 51.9% (37.8%, 65.7%) and 50.0% (36.1%, 63.9%), respectively. The overall survival (OS) for full analysis set (FAS) at day 28, 56, 100, 360 for the entire cohort were 94.4% (83.8%, 98.2%), 88.9% (76.9%, 94.9%), 79.6% (66.2%, 88.2%), 65.8% (51.1%, 77.0%) respectively. Treatment was well tolerated, and no infusion-related toxicity or treatment-related serious adverse events were observed. In this multicenter single-arm study, hUC-MSC PLEB001 plus anti-CD25 monoclonal antibody therapy was associated with clinically meaningful response rates and an acceptable safety profile in patients with SR-GI-aGVHD. These findings support further evaluation of MSC-based approaches within multimodal treatment algorithms for this challenging condition. Trial registration: Registry: Chinese Clinical Trial Registry, TRN: ChiCTR2300073965, Registration date: 2023-07-26 (retrospectively registered).

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