Remestemcel-L-rknd Approved for Pediatric Patients With Steroid-Refractory Acute Graft-Versus-Host Disease
Expert Perspectives · Keira Smith · 2024-12-26
The FDA has granted approval to remestemcel-L-rknd (Ryoncil®, Mesoblast, Inc.), an allogeneic bone marrow–derived mesenchymal stromal cell (MSC) therapy, for pediatric patients aged 2 months and older with steroid-refractory acute graft-versus-host disease (GVHD). Remestemcel-L is the first MSC therapy to be approved by the FDA.
Why Is the Approval of Remestemcel-L Important?
“Acute GHVD is a major obstacle to the overall success of allogeneic hematopoietic stem cell transplantation (HSCT),” wrote Joanna Kurtzberg, MD, Director of Pediatric Transplant and Cellular Therapy Program at Duke Cancer Institute, and colleagues, in their published results of the MSB-GVHD001 trial (NCT02336230), on which approval was based. “Despite overall improvement in transplantation outcomes, patients who develop acute GVHD and subsequently fail to respond to initial steroid therapy continue to have high morbidity and mortality, in large part because there are no effective treatment options for these patients. The biological activity of MSCs provides a mechanistic rationale for their investigational use in acute GVHD.”
Investigating Remestemcel-L in MSB-GVHD001
Efficacy was investigated in the phase 3, multicenter, prospective, single-arm study that enrolled 54 pediatric patients between 2 months and 17 years of age. Patients had steroid-refractory acute GVHD, defined as acute GVHD progressing within three days or not improving within seven consecutive days of methylprednisone, after undergoing HSCT. The primary end points were overall response rate (ORR) at Day 28, including complete and partial responses, and duration of overall response.
At Day 28, remestemcel-L produced an ORR of 70%, including 30% complete responses and 41% partial responses. The median duration of response calculated from response at Day 28 to either progression, new systemic therapy for acute GVHD, or any cause death, was 54 days.
Adverse Events
The most common nonlaboratory adverse events, experienced by ≥20% of patients, were viral infectious disorders, bacterial infectious disorders, pathogen-unspecified infection, pyrexia, hemorrhage, edema, abdominal pain, and hypertension.
Putting It Into Context
“This study provides robust, prospective evidence of the safety, tolerability, and efficacy of remestemcel-L as first-line therapy after initial steroid failure in pediatric steroid-refractory acute GVHD,” concluded Dr. Kurtzberg and colleagues in their publication. “In conclusion, MSB-GVHD001 and the MSB-GVHD002 follow-up study, taken together with positive findings of other remestemcel-L studies in aGVHD, confirm the safety profile and demonstrate the efficacy and durability of remestemcel-L treatment for steroid-refractory acute GVHD in the pediatric population.”
Dosing Instructions
The recommended dose of remestemcel-L is 2 x 106 MSC/kg body weight per intravenous infusion, given twice a week for four consecutive weeks, with a total of eight infusions administered at least three days apart. Treatment may be continued based on response at 28 days after initial cycle of remestemcel-L.