Remestemcel-L-rknd is approved by the USFDA for steroid-refractory acute graft versus host disease in pediatric patients

On December 18, 2024, the Food and Drug Administration sanctioned remestemcel-L-rknd (Ryoncil, Mesoblast, Inc.), an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy, for steroid-refractory acute graft versus host disease (SR-aGVHD) in pediatric patients aged 2 months and older. Ryoncil is the inaugural MSC therapy approved by the FDA.

Efficacy and Safety

The efficacy was assessed in MSB-GVHD001 (NCT02336230), a multicenter, prospective, single-arm trial involving 54 pediatric patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Patients exhibited Grade B to D SR-aGVHD, omitting Grade B skin-only cases, as per the International Blood and Marrow Transplantation Registry Severity Index Criteria.

SR-aGVHD was characterized as aGVHD that either advanced after 3 days or failed to improve within 7 consecutive days of methylprednisolone administration (2 mg/kg/day or its equivalent). Patients who underwent second-line aGVHD treatment before screening were excluded.

The primary efficacy outcome indicators were the overall response rate (ORR) at Day 28 and the duration of the overall response. The Overall Response Rate (ORR) encompassed complete response (CR) and partial response (PR) rates.

The overall response rate (ORR) at Day 28 was 70% (95% confidence interval: 56.4, 82.0), comprising a complete response (CR) rate of 30% (95% CI: 18.0, 43.6) and a partial response (PR) rate of 41% (95% CI: 27.6, 55.0). The median duration of response, measured from Day 28 to progression, initiation of new systemic medication for aGVHD, or any cause of death, was 54 days (range 7 to 159+).

The predominant nonlaboratory adverse effects (incidence ≥20%) included viral infections, bacterial infections, nonspecific infections, fever, bleeding, edema, stomach pain, and hypertension.

The advised dosage is 2 X 10^6 MSC/kg of body weight administered via intravenous infusion biweekly for 4 consecutive weeks, totaling 8 infusions. Infusions are given a minimum of three days apart. Treatment may persist contingent upon the response observed 28 days following the initial administration of remestemcel-L-rknd.