TY - JOUR
T1 - 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
AU - for the MSB-GVHD001/002 Study Group
AU - Kurtzberg, Joanne
AU - Abdel-Azim, Hisham
AU - Carpenter, Paul
AU - Chaudhury, Sonali
AU - Horn, Biljana
AU - Mahadeo, Kris
AU - Nemecek, Eneida
AU - Neudorf, Steven
AU - Prasad, Vinod
AU - Prockop, Susan
AU - Quigg, Troy
AU - Satwani, Prakash
AU - Cheng, Annie
AU - Burke, Elizabeth
AU - Hayes, Jack
AU - Skerrett, Donna
N1 - Funding Information:
Financial disclosure: This study was funded by Mesoblast International Sàrl.
Funding Information:
The authors thank all the physicians, nurses, physician extenders, and clinical research nurses caring for the patients and collecting the data from patients on this study. In addition, they thank the hospital stem cell transplant laboratories that received, stored, thawed, and prepared remestemcel-L for administration. The authors acknowledge Ulrike Rawiel, MS (Mesoblast, Inc.), for assistance with data management. List of participants in the MSB-GVHD001/002 Study Group: Hisham Abdel-Azim, MD, Children's Hospital of Los Angeles, CA; Roberta Adams, MD, Phoenix Children's Hospital, Phoenix, AZ; Victor Aquino, MD, University of Texas Southwest Medical Center, Dallas, TX; Joel Brochstein, MD, Cohen Children's Medical Center of New York, New Hyde Park, NY; Mitchell Cairo, MD, New York Medical College, Valhalla, NY; Paul Carpenter, MD, Fred Hutchinson Cancer Center, Seattle, WA; Emi Caywood, MD, Los Angeles, CA; Nemours Alfred I. duPont Hospital for Children, Wilmington, DE; Sonali Chaudhury, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Ken DeSantes, MD, University of Wisconsin, Madison, WI; Christopher Dvorak, MD, UCSF Benioff Children's Hospital, San Francisco, CA; John Fort, MD, University of Florida Shands Cancer Center, Gainesville, FL; Robert Greiner, MD, Penn State Hershey Medical Center, Hershey, PA; Kamar Godder, MD, Miami Children's Research Institute, Miami, FL; Rabi Hanna, MD, Cleveland Clinic, Cleveland, OH; Biljana Horn, MD, UCSF Benioff Children's Hospital, San Francisco, CA; Michelle Hudspeth, MD, Medical University of South Carolina, Charleston, SC; Michael Joyce, MD, Nemours Children's Specialty Care, Jacksonville, FL; Amy Keating, MD, Children's Hospital Colorado Center for Cancer/Blood Disorder, Aurora, CO; Sandhya Kharbanda, MD, UCSF Benioff Children's Hospital, San Francisco, CA; Joanne Kurtzberg, MD, Duke University Medical Center, Durham, NC; Jason Law, MD, Tufts Medical Center, Boston, MA; David Loeb, MD, The Children's Hospital at Montefiore, Bronx, NY; Kris Mahadeo, MD, Albert Einstein College of Medicine, New York, NY; Deepa Manwani, MD, The Children's Hospital at Montefiore, Bronx, NY; Alicia McFarren, MD, Children's Hospital of Los Angeles, CA; Gail Megason, MD, University of Mississippi Medical Center, Jackson, MS; Gary Myers, MD, Children's Mercy Hospital, Kansas City, MO; Eneida Nemecek, MD, Doernbecher Children's Hospital and Oregon Health & Science University, Portland, OR; Steven Neudorf, MD, Children's Hospital of Orange County, Orange, CA; Benjamin Oshrine, MD, Johns Hopkins All Children's Hospital, St. Petersburg, FL; Susan Prockop, MD, Memorial Sloan Kettering Cancer Center, New York, NY; Troy Quigg, DO, Texas Transplant Institute, Methodist Children's Hospital, San Antonio, TX; Robert Sanders, MD, Methodist Children's Hospital, San Antonio, TX; Prakash Satwani, MD, Columbia University Medical Center, New York, NY; Sureya Savasan, MD, Children's Hospital of Michigan, Detroit, MI; Shalini Shenoy, MD, Washington University St. Louis Children's Hospital, St. Louis, MO; Julie-An Talano, MD, Medical College of Wisconsin, Milwaukee, WI; Christina Wiedl, MD, Virginia Commonwealth University, Richmond, VA; Randy Windreich, MD, Children's Hospital of Pittsburgh of UPMC, Pittsburg, PA; Lolie Yu, MD, Children's Hospital of New Orleans, New Orleans, LA; Annie Cheng, MS, Mesoblast Inc. New York, NY; Elizabeth Burke, MSN, Mesoblast Inc. New York, NY; Jack Hayes, MS, Mesoblast Inc. New York, NY; Donna Skerrett, MD, MS, Mesoblast Inc. New York, NY. Financial disclosure: This study was funded by Mesoblast International S?rl. Conflict of interest statement: There are no conflicts of interest to report. Financial disclosure: See Acknowledgments on page 853.
Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - Acute graft-versus-host disease
KW - Allogeneic
KW - Hematopoietic stem cell transplantation
KW - Mesenchymal stromal cells
KW - Remestemcel-L
KW - Steroid
UR - http://www.scopus.com/inward/record.url?scp=85082457473&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082457473&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2020.01.018
DO - 10.1016/j.bbmt.2020.01.018
M3 - Article
C2 - 32018062
AN - SCOPUS:85082457473
VL - 26
SP - 845
EP - 854
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 5
ER -