Study 275: Updated Expanded Access Program for Remestemcel-L in Steroid-Refractory Acute Graft-versus-Host Disease in Children

for the MSB-275 Study Group

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Clinical outcomes in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD) are generally poor, with a high mortality rate and limited therapeutic options. Here we report our updated investigational experience with mesenchymal stromal cell (MSC) therapy with remestemcel-L in a multicenter expanded access protocol (ClinicalTrials.gov identifier NCT00759018) in 241 children with aGVHD who failed to respond to steroids with or without other secondary and tertiary immunosuppressive therapies. A total of 241 children with grade B-D SR-aGVHD were enrolled at 50 sites in 8 countries and received 8 biweekly i.v. infusions of human MSCs, 2 × 106 per kg for 4 weeks, with an option for an additional 4 weekly infusions after day +28 for subjects who achieved either a partial response (PR) or mixed response. The mean age of the subjects was 9.6 years; 39% were female, and 60% were white. Most of the subjects had grade C (30%) or grade D (50%) disease, and in most cases, the subjects had failed to respond to other immunosuppressive agents after failing steroids. The primary endpoint was overall response (OR; the sum of complete response [CR] and PR) at day +28. Across all subjects, a 28-day OR was observed in 157 patients (65.1%), with 34 (14.1%) achieving CR and 123 (51.3%) achieving PR. Stratified by aGVHD grade at baseline, the OR rate at day +28 was 72.9% for patients with aGVHD grade B, 67.1% for those with aGVHD grade C, and 60.8% for those with aGVHD grade D. Survival through day +100, a secondary endpoint of the study, was 66.9% (n = 160 of 239). Importantly, survival through day +100 was significantly greater in subjects who achieved a day +28 OR compared with nonresponders (82.1% versus 38.6%; P < .001, log-rank test). Remestemcel-L safety was generally well tolerated, with no infusional toxicity and no identified safety concerns. In summary, this update to the remestemcel-L expanded access program confirms the reported clinical and survival benefits of remestemcel-L therapy in children with aGVHD who have exhausted all conventional therapeutic options.

Original languageEnglish (US)
Pages (from-to)855-864
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume26
Issue number5
DOIs
StatePublished - May 2020

Funding

Financial disclosure: This study was funded by Mesoblast International Sàrl. The authors thank all the patients and their parents for their participation in this EAP and for allowing us to share their data in this article, all the participating physicians and transplantation center staff for their participation in this study, the transplant and stem cell laboratories for product handling and preparation for administration, and Ulrike Rawiel (Mesoblast) for assistance with data management. Financial disclosure: This study was funded by Mesoblast International Sàrl. Conflict of interest statement: There are no conflicts of interest to report. Roberta Adams, MD, Phoenix Children's Hospital, Phoenix, AZ; Sanjay Ahuja, MD, University Hospitals Case Medical Center, Cleveland, OH; Martin Andreansky, MD, University of Miami School of Medicine; Miami, FL; James Bradley Ball, MD, University of Alabama, Birmingham, AL; Raymond Barfield MD, St. Jude Children's Research Hospital, Memphis, TN; Paul Carpenter, MD, Fred Hutchinson Cancer Center, Seattle, WA; Sonali Chaudhury, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Roland Chu, MD, Children's Hospital of Michigan, Detroit, MI; Jignesh Dalal, MD, Children's Mercy Hospitals and Clinics, Kansas City, MO; Kenneth DeSantes, MD, University of Wisconsin American Family Children's Hospital, Madison, WI; Jennifer Domm, MD, Vanderbilt University Medical Center, Nashville, TN; John Doyle, MD, Hospital for Sick Children, Toronto, Ontario, Canada; Pierre Teira MD, CHU Sainte Justine, Montreal, Quebec Canada; Ayman El-Sheikh, MD, University of Iowa Hospitals and Clinics Iowa City, IA; Christopher Fraser, MD, Royal Children's Hospital, Brisbane, Queensland, Australia; Alfred P. Gillio, MD, Hackensack University Medical Center Hackensack, NJ; Andrew Gilman, MD, Carolinas Medical Center, Charlotte, NC; Paul Gordon, MD, Florida Hospital for Children, Orlando FL; Rakesh Goyal, MD, Children's Hospital of Pittsburgh, Pittsburgh, PA; Biljana Horn, MD, UCSF Children's Hospital, San Francisco, CA; Rachael Hough, MD, University College of London, London, United Kingdom; Michelle Hudspeth, MD, Medical University of South Carolina, Charleston, SC; David Jacobsohn, MD, Children's National Medical Center, Washington, D.C.; Kirsi Jahnukainen, MD, Helsinki University Central Hospital Children's Hospital, Helsinki, Finland; Michael Joyce, MD, PhD, Nemours Children's Clinic, Jacksonville, FL; Joanne Kurtzberg, MD, Duke University Medical Center, Durham, NC; Jason Law, MD, Tufts Medical Center, Boston MA; Kathryn Leung, MD, Texas Children's Hospital, Houston, TX; Victor Lewis, MD, Alberta Children's Hospital, Calgary, Alberta Canada; Kenneth Lucas, MD, Penn State Hershey Medical Center, Hershey, PA; John M. McCarty, MD, Virginia Commonwealth University, Richmond, VA; David Mitchell, MD, Montreal Children's Hospital, Montreal, Quebec, Canada; John Moppett, MD, Bristol Royal Hospital for Children, Bristol, UK; Gary Douglas Myers MD, Mercy Hospitals and Clinics, Kansas City, MO; Eneida Nemecek, MD, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR; Steven Neudorf, MD, Children's Hospital of Orange County, Orange, CA; Vinod Prasad, MD Duke University Medical Center, Durham, NC; Susan Prockop, MD, Memorial Sloan Kettering Cancer Center, New York, NY; Michael Pulsipher, MD, University of Utah, Salt Lake City, UT; Troy Quigg, DO, Texas Transplant Institute, San Antonio, TX; Kent Robertson, MD, James Whitcomb Riley Hospital for Children, Indianapolis, IN; Jose Miguel Couselo Sanchez, MD, Hospital Clinico Universitario, Santiago de Compostela, Spain; Prakash Satwani, MD, Columbia University Medical Center, New York, NY; Shalini Shenoy, MD, Washington University, St. Louis Children's Hospital St. Louis, MO; Geoff Shenton, MD, St. James University Hospital; Sandeep Soni, MD, Nationwide Children's Hospital, Columbus, OH; Michael J. Sullivan, MD, Children's Haematology/Oncology Centre, Christchurch, New Zealand; Julie-An Talano, MD, Medical College of Wisconsin, Milwaukee, WI; Brandon Triplett, MD, Cardinal Glennon Children's Medical Center, St. Louis, MO; Giuseppe Visani, MD, Universita degli Studi di Pesaro, Pesaro, Italy; Randy Windreich MD, Laura Worth, MD, University of Texas, MD Anderson Cancer Center, Houston, TX; Lolie C. Yu, MD, Children's Hospital New Orleans, LA Financial disclosure: See Acknowledgments on page 862.

Keywords

  • Acute graft-versus-host disease
  • Allogeneic hematopoietic cell transplantation
  • Compassionate use
  • Mesenchymal stromal cell
  • Remestemcel-L
  • Steroid

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Fingerprint

Dive into the research topics of 'Study 275: Updated Expanded Access Program for Remestemcel-L in Steroid-Refractory Acute Graft-versus-Host Disease in Children'. Together they form a unique fingerprint.

Cite this