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

Joanne Kurtzberg, Hisham Abdel-Azim, Paul Carpenter, Sonali Chaudhury, Biljana Horn, Kris Mahadeo, Eneida Nemecek, Steven Neudorf, Vinod Prasad, Susan Prockop, Troy Quigg, Prakash Satwani, Annie Cheng, Elizabeth Burke, Jack Hayes, Donna Skerrett, MSB-GVHD001/002 Study Group, Joanne Kurtzberg, Hisham Abdel-Azim, Paul Carpenter, Sonali Chaudhury, Biljana Horn, Kris Mahadeo, Eneida Nemecek, Steven Neudorf, Vinod Prasad, Susan Prockop, Troy Quigg, Prakash Satwani, Annie Cheng, Elizabeth Burke, Jack Hayes, Donna Skerrett, MSB-GVHD001/002 Study Group

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.

Keywords: Acute graft-versus-host disease; Allogeneic; Hematopoietic stem cell transplantation; Mesenchymal stromal cells; Remestemcel-L; Steroid.

Conflict of interest statement

Conflict of interest statement: There are no conflicts of interest to report.

Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.
Figure 1.
Study design.
Figure 2.
Figure 2.
Kaplan-Meier plot of overall survival through day 180 from initiation of remestemcel-L therapy (day 0). (A) Stratified by overall response at day 28 (responders and nonresponders). (B) Stratified by Minnesota risk category (high risk or standard risk). (C) Stratified by baseline aGVHD grade.

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Source: PubMed

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