ASH 2018 | MSC-FFM for the treatment of pediatric and adult patients with steroid-refractory graft-versus-host disease

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that showed promising activity for the treatment of steroid-resistant acute graft-versus-host disease (SR aGvHD). MSCs modulate immune responses by secreting soluble factors that can modify the stimulation, proliferation and maturation of T- and B-lymphocytes, natural killer cells, and dendritic cells. Furthermore, MSCs also induce the differentiation of regulatory T cells and regulate the Th1/Th2 ratio. At present, there are several ongoing randomized trials investigating the impact of MSCs on GvHD prevention or treatment.

At the 60^th American Society of Hematology Annual Meeting & Exposition, Peter Bader from Hospital for Children and Adolescents; Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt, Germany, presented treatment data of pediatric and adult patients with either SR GvHD (27%) or GvHD treated with MSC-Frankfurt am Main (MSC-FFM), a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses developed by Professor Bader and colleagues.

Patients and methods

• N = 61 pediatric patients
  • Median age = 7.7 years (range, 0.5–0)
• N = 31 adult patients
  • Median age = 42.4 years (range, 18.4–65.6)
• Patients from 23 centers in 6 countries were included in this study
• Severe GvHD: 37% grade III, 59% grade IV
• Donors: MSD (n = 21, 23%), MUD (n = 56, 61%), haploidentical ( n= 14, 15%), and MMUD (n = 1, 1%)
• Myeloablative conditioning with TBI-(treosulfan, busulfan and fludarabine) based regimen
• 89% of patients had received immunosuppression for GvHD prophylaxis
• Recommended dose: 4 weekly doses of 1-2M MSC/kg
• Patients received 3 doses on average

Key findings

• Response 28 days after MSC:
  • CR: 28%
  • PR: 54%
  • NR: 15%
• Response at last follow-up:
  • CR: 51%
  • PR: 30%
  • NR: 17%
• Day-28 response rates were highly predictive of long-term responsiveness
• Six patients relapsed and died
• Twenty-eight deaths were treatment-related
• 6-month overall survival for children and adults: 68% and 54%, respectively
• Adverse events: headache, nausea/vomiting were reported shortly after infusion

Professor Bader concluded that MSC-FFM is effective for the treatment of severe pediatric and adult advanced GvHD. “The very low relapse mortality may suggest that severe GvHD effectively suppresses leukemic recurrence.” A randomized trial for the treatment of SR aGvHD is planned to start in 2019.