MSCs for the treatment of SR-aGvHD

Findings from a systematic review and meta-analysis, investigating mesenchymal stromal cells (MSCs) for the management of steroid-refractory acute graft-versus-host disease (SR-aGvHD), were recently published in Scientific Reports by Debes et al. Data from 16 clinical trials (N = 1,301) were analyzed. Primary endpoints included safety of MSC intravenous infusion, overall response rate (ORR), and overall survival (OS). However, due to the limited number of placebo-controlled trials, a meta-analysis of adverse events (AEs) related to MSCs was not possible. Secondary endpoints included complete response (CR) rate, relapse rate (RR), and organ-specific response.  

Key data: AEs were limited, including nausea and vomiting (n = 1) and headache (n = 1). Serious AEs and Grade ≥3 AEs were reported, although these were comparable with control cohorts. The ORR was 61% (95% confidence interval [CI], 0.54–0.67) and the CR rate was 29% (95% CI, 0.23–0.36). At a median of 12 months, the OS rate was 34% (95% CI, 0.29–0.4); following assessment of the controlled trials (MSC infusion, n = 348; control, n = 234), OS rate post-MSC infusion was comparable with control (overall ratio [OR], 1.15; 95% CI, 0.81–1.62). Frequent MSC infusions (≥4 within 28 days) achieved superior ORR (64% vs 47%; p = 0.04) and OS (40% vs 22%; p < 0.0001) compared with infrequent infusions, and a dose of 1 × 10⁶ cells/kg was comparable with ≥2 × 10⁶ cells/kg. 

Key learning: MSCs represent an effective therapeutic option for SR-aGvHD, with optimal outcomes achieved using 1 × 10⁶ cells/kg administered at least four times within the first 28 days of treatment.