A recent exploratory study published in BMC Medicine has shed light on the potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in treating steroid-refractory acute graft-versus-host disease (SR-aGVHD). The multi-center, double-blinded trial conducted across seven Chinese centers, suggests that hUC-MSCs could offer a significant therapeutic benefit for patients who have not responded to traditional steroid treatments.
The study enrolled patients aged 13 to 70 with hematologic malignancies who developed SR-aGVHD after undergoing allogeneic hematopoietic stem cell transplantation. Participants were randomized in a 1:1 ratio to receive either hUC-MSCs or a placebo, in addition to a second-line agent (excluding ruxolitinib) chosen by each center. The primary endpoint was the overall response rate (ORR) at day 28, defined as the proportion of patients achieving complete or partial response without needing additional immunosuppressive agents.
Study Design and Methods
The trial employed a rigorous double-blind design, with patients receiving either hUC-MSCs at a dose of 1.0 × 10^6 cells/kg intravenously twice a week for four weeks, or a placebo. Patients who achieved complete response (CR), no response (NR), or disease progression (PD) at day 28 received eight infusions, while those with partial response (PR) received additional infusions for another four weeks. The hUC-MSCs, branded as PLEB001, were sourced from healthy donors and characterized by specific cell surface markers and secretion of immunomodulatory factors.
Key Findings
The primary endpoint analysis revealed a higher ORR at day 28 in the hUC-MSC group compared to the control group. Secondary endpoints, including ORR at day 56, disease control rate (DCR), and complete response rates at both day 28 and day 56, also showed favorable trends in the hUC-MSC arm. The study also assessed overall survival (OS), cumulative incidence of relapse, non-relapse mortality (NRM), chronic GVHD (cGVHD), and failure-free survival (FFS).
Clinical Implications
These findings suggest that hUC-MSCs could represent a valuable addition to the treatment armamentarium for SR-aGVHD, a condition with limited therapeutic options. The study's authors emphasize the need for further research to confirm these results in larger, phase 3 clinical trials and to better understand the mechanisms of action of hUC-MSCs in the context of GVHD.
Safety Profile
The safety profile of hUC-MSCs appeared to be acceptable, with adverse events (AEs) and serious adverse events (SAEs) monitored throughout the study. Infusion toxicity was also assessed within 14 days after the last infusion.
Limitations
It is important to note that this was an exploratory phase 2 study, and the sample size was not designed to establish statistical significance for efficacy endpoints. Further, the study was conducted exclusively in Chinese centers, which may limit the generalizability of the findings to other populations.
