Remestemcel-L Now an FDA Approved Treatment for Pediatric SR-aGVHD

The FDA has granted approval for remestemcel-L-rknd (Ryoncil) for the treatment of pediatric patients aged 2 months and older with steroid-refractory acute graft versus host disease (SR-aGVHD).¹

“The potential impact of having Ryoncil available for pediatric patients with steroid resistant acute graft versus host disease is enormous.  Until this approval, there were no FDA approved treatments for children under 12 years of age and the majority of children with this condition did not survive.  In clinical trials, Ryoncil was shown to be significantly effective, lessening suffering and improving survival overall.  Ryoncil, which is an intravenous therapy, is also very well tolerated in children and does not produce any untoward side effects,” Joanne Kurtzberg, MD, Jerome Harris Distinguished Professor of Pediatrics, professor of Pathology, director, Marcus Center for Cellular Cures (MC3), director, Carolinas Cord Blood Bank, co-director, Stem Cell Transplant Laboratory, and president, Cord Blood Association at Duke University School of Medicine told Blood Cancers Today.

Approval of the biologics license application for remestemcel-L was granted by the FDA on the basis of findings from the phase 3 MSB-GVHD001 clinical trial (NCT02336230).

“The MSB-GVHD001 study showed striking results with ORR of about 7o% in pediatric patients with steroid refractory GVHD with about 30% of these responses being complete responses. Most importantly there were no additional immune suppressive side effects such as increased rate of infections. These are known complications of current therapies for GVHD,” Sonali Chaudhury, MD of Ann & Robert H. Lurie Children’s Hospital of Chicago, told Blood Cancers Today.

The study included 54 pediatric patients with SR-aGVHD who had undergone allogeneic hematopoietic stem cell transplantation and whose disease was grade B to D. The patients received remestemcel-L at 2 × 10⁶ cells/kg twice weekly for 4 weeks.

The exact overall response rate observed was 70% (95% CI, 56.4-82.0) at day 28, and the complete response rate was 30% (95% CI, 18.0-43.6). Partial responses to remestemcel-L were observed in 41% of patients (95% CI, 27.6-55.0). In terms of response durability, the time from response at day 28 to events of disease progression, new systemic therapy for aGVHD, or death of any cause was 54 days (range, 7–159+ days).^1,2

The overall survival rate was 74.1% at day 100 and 68.5% at day 180. Furthermore, the study showed that response was predictive of improvement in overall survival (OS). Survival was determined to be significantly improved among patients who responded to therapy by day 28 (86.8% OS rate) compared with those who did not respond by day 100 (47.1% OS rate; P =.0001). The same was shown through day 180 with a 78.9% OS among responders versus 43.8% among nonresponders (P =.0003).²

In terms of safety, the most common nonlaboratory adverse reactions were viral infectious disorders, bacterial infectious disorders, infection with  an unspecified pathogen, pyrexia, hemorrhage, edema, abdominal pain, and hypertension. These adverse reactions were seen in 20% or more of patients treated with remestemcel-L.¹

Based on study data and the priority review of the biologic license application for remestemcel-L, the FDA-recommended dose is 2 × 10⁶ mesenchymal stromal cells /kg body weight per intravenous infusion.  Remestemcel-L is to be administered twice a week for four consecutive weeks for a total of eight infusions. Infusions must be administered three days apart and may be continued based on response at 28 days after the initial infusion.

“Further studies specially in liver, gastrointestinal aGVHD and possibly chronic GVHD will be important next areas of focus for clinical research,” said Chaudhary, section head, Stem Cell Transplantation and Cellular Therapies, and professor of Pediatrics (Hematology, Oncology and Stem Cell Transplantation) at Northwestern University Feinberg School of Medicine.

References

1. FDA approves remestemcel-L-rknd for steroid-refractory acute graft versus host disease in pediatric patients. FDA. December 18, 2024. Accessed December 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-remestemcel-l-rknd-steroid-refractory-acute-graft-versus-host-disease-pediatric
2. Kurtzberg J, Abdel-Azim H, Carpenter P, et al. A phase 3, single-arm, prospective study of remestemcel-l, ex vivo culture-expanded adult human mesenchymal stromal cells for the treatment of pediatric patients who failed to respond to steroid treatment for acute graft-versus-host disease. Biol Blood Marrow Transplant. 2020;26(5):845-854. doi: 10.1016/j.bbmt.2020.01.018