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.
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2020-05
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Abstract
Steroid-refractory acute graft-versus-host disease (SR-aGVHD) following hematopoietic cell transplantation (HSCT) is associated with poor clinical outcomes. Currently, there are no safe and effective therapies approved for use in the pediatric population under the age of 12 years. Accordingly, there is an urgent need for new treatments that are safe, well tolerated, and effective in managing this debilitating and potentially fatal complication of HSCT. In early phase clinical trials, mesenchymal stromal cells (MSCs) have demonstrated efficacy in the treatment of acute GVHD (aGVHD) in pediatric patients. We now report the results of a phase 3, prospective, single-arm, multicenter study (NCT02336230) in 54 children with primary SR-aGVHD who were naive to other immunosuppressant therapies for aGVHD treated with MSC product (remestemcel-L) dosed at 2 × 106 cells/kg twice weekly for 4 weeks. Remestemcel-L therapy significantly improved day 28 overall response rate (OR) compared with the prespecified control OR value of 45% (70.4% versus 45%, P = .0003). The statistically significant OR (70.4%) was sustained through day 100, including an increase in complete response from 29.6% at day 28 to 44.4% at day 100. Overall survival was 74.1% at day 100 and 68.5% at day 180. Overall response in all participants at day 28 was highly predictive of improved survival through 180 days, and survival was significantly greater in day 28 responders compared with nonresponders through day 100 (86.8% versus 47.1% for responders and nonresponders, respectively, P = .0001) and through day 180 (78.9% versus 43.8%, P = .003). Remestemcel-L was well tolerated with no identified infusion-related toxicities or other safety concerns. 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 SR-aGVHD.
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Kurtzberg, Joanne, Hisham Abdel-Azim, Paul Carpenter, Sonali Chaudhury, Biljana Horn, Kris Mahadeo, Eneida Nemecek, Steven Neudorf, et al. (2020). 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. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 26(5). pp. 845–854. 10.1016/j.bbmt.2020.01.018 Retrieved from https://hdl.handle.net/10161/24567.
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Kris Mahadeo
As a committed life-long learner, I am awed by the continued advancements in the field of pediatric transplant and cellular therapy (PTCT). Following completion of my PTCT fellowship training at Duke, I have developed a career dedicated to expanding indications for PTCT and improving associated outcomes. I have a special interest in the mitigation of endotheliopathies and continue to lead global harmonization efforts related to management of toxicities of therapy. As the Division Chief of PTCT at Duke, I am committed to the ensuring our patients receive state of the art care with access to innovative research protocols that change the field. We are committed to training the next generation of physicians in our field with a commitment to global partnerships to improve care for patients across the world.
Vinod K. Prasad
1. Expanding the role of umbilical cord blood transplants for inherited metabolic disorders.
2. Impact of histocompatibility and other determinants of alloreactivity on clinical outcomes of unrelated cord blood transplants.
3. Studies to analyse the impact of Killer Immunoglobulin receptors on the outcomes of hematopoietic stem cell transplantation utilizing haploidentical, CD34 selected, familial grafts.
4. Propective longitudinal study of serial monitoring of adenovirus in allogenic transpants(SMAART)patients.
5. Use of mesenchymal stem cells for the treatment of GVHD
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