Treatment of Severe Acute Graft-Versus-Host Disease Refractory to Multiple Lines of Therapy: Real-World Data from 317 Adults Treated with the Multiple-Donor Bone Marrow-Derived Mesenchymal Stromal Cell Preparation Tomostrocel
Abstract
Patients with severe, multi-refractory acute graft-versus-host disease (aGvHD) after hematopoietic stem cell transplantation (HSCT) have a dismal prognosis, but mesenchymal stromal cells (MSC) have emerged as a promising treatment option. A unique bone marrow-derived off-the-shelf MSC product generated from multiple donors, ie, human allogeneic MSCs DRK-BaWü-He-FFM (tomostrocel, formerly referred to as MSC-FFM), is currently under development. Tomostrocel is also distributed under Hospital Exemption in Germany and Named Patient Use elsewhere in Europe, with data of treated patients captured in a dedicated surveillance program. The purpose of this retrospective analysis of prospectively collected surveillance data is to describe outcomes of adult patients with multi-refractory aGvHD treated with tomostrocel in clinical practice. We retrospectively assessed real-world data of 317 adults with refractory aGvHD treated with tomostrocel in multiple transplant centers across Europe between 2017 and 2025. This uncontrolled observational study includes pseudonymized data actively collected for all patients receiving tomostrocel outside of clinical trials. Evaluated outcomes include response rates at different time points, overall survival, and adverse reactions. Patients were followed for 24 mo from first administration of tomostrocel. Median follow-up since the last HSCT was 26.9 mo (range 2.4 to 63.2 mo). aGvHD was mostly severe (4, 37, and 55% grade II, III, and IV, respectively), and a median of three (reported range 0 to 10) prior therapeutic lines had been exhausted, including ruxolitinib in 75% of patients. The predominant site of aGvHD was the lower gastrointestinal tract (30%/52% with Stage 3/4). The overall response rate in this heavily pretreated cohort at Day 28 was 45% (95% confidence interval [CI] 40% to 51%). Probability of overall survival (OS) at 6, 12, and 24 mo was 44% (95% CI 38% to 49%), 33% (95% CI 27% to 38%), and 28% (95% CI 23% to 34%), respectively (median 4.3 mo). Several subgroup analyses suggested signs of efficacy compared to expected outcomes according to the literature. The safety profile of tomostrocel was favorable, consistent with previous reports. This real-world data analysis showed several efficacy signals and a reassuring safety profile for tomostrocel in multi-refractory aGvHD. Response on Day 28 was predictive for OS, regardless of prior exposure to ruxolitinib. Despite the inherent limitations associated with real-world data collection, these findings suggest that tomostrocel represents a promising treatment option for heavily pretreated and severely ill steroid-refractory aGvHD patients. Results of the ongoing randomized controlled trials are eagerly awaited.
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BibTeX
@article{verbeek2026treatment,
title = {{Treatment of Severe Acute Graft-Versus-Host Disease Refractory to Multiple Lines of Therapy: Real-World Data from 317 Adults Treated with the Multiple-Donor Bone Marrow-Derived Mesenchymal Stromal Cell Preparation Tomostrocel}},
author = {Mareike Verbeek and Halvard Bonig and Francis Ayuk and Gesine Bug and Maud D’aveni-Piney and Daniela Heidenreich and Peter Herhaus and Udo Holtick and Igor Kos and William Krüger and Maria Teresa Lupo-Stanghellini and Thomas Mika and Charlotte Neuerburg and Elena Osswald and Victoria Panagiota and Christian Reicherts and Christoph Schmid and Micha Srour and Friedrich Stölzel and Michael Tribanek and Friederike Wortmann and Gerald Wulf and Anke Zens and Robert Zeiser},
journal = {Transplantation and Cellular Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.jtct.2026.09.021},
url = {https://hal.univ-lorraine.fr/hal-05787696v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Treatment of Severe Acute Graft-Versus-Host Disease Refractory to Multiple Lines of Therapy: Real-World Data from 317 Adults Treated with the Multiple-Donor Bone Marrow-Derived Mesenchymal Stromal Cell Preparation Tomostrocel
AU - Mareike Verbeek
AU - Halvard Bonig
AU - Francis Ayuk
AU - Gesine Bug
AU - Maud D’aveni-Piney
AU - Daniela Heidenreich
AU - Peter Herhaus
AU - Udo Holtick
AU - Igor Kos
AU - William Krüger
AU - Maria Teresa Lupo-Stanghellini
AU - Thomas Mika
AU - Charlotte Neuerburg
AU - Elena Osswald
AU - Victoria Panagiota
AU - Christian Reicherts
AU - Christoph Schmid
AU - Micha Srour
AU - Friedrich Stölzel
AU - Michael Tribanek
AU - Friederike Wortmann
AU - Gerald Wulf
AU - Anke Zens
AU - Robert Zeiser
PY - 2026
DA - 2026/10/08
JO - Transplantation and Cellular Therapy
DO - 10.1016/j.jtct.2026.09.021
UR - https://hal.univ-lorraine.fr/hal-05787696v1
AB - Patients with severe, multi-refractory acute graft-versus-host disease (aGvHD) after hematopoietic stem cell transplantation (HSCT) have a dismal prognosis, but mesenchymal stromal cells (MSC) have emerged as a promising treatment option. A unique bone marrow-derived off-the-shelf MSC product generated from multiple donors, ie, human allogeneic MSCs DRK-BaWü-He-FFM (tomostrocel, formerly referred to as MSC-FFM), is currently under development. Tomostrocel is also distributed under Hospital Exemption in Germany and Named Patient Use elsewhere in Europe, with data of treated patients captured in a dedicated surveillance program. The purpose of this retrospective analysis of prospectively collected surveillance data is to describe outcomes of adult patients with multi-refractory aGvHD treated with tomostrocel in clinical practice. We retrospectively assessed real-world data of 317 adults with refractory aGvHD treated with tomostrocel in multiple transplant centers across Europe between 2017 and 2025. This uncontrolled observational study includes pseudonymized data actively collected for all patients receiving tomostrocel outside of clinical trials. Evaluated outcomes include response rates at different time points, overall survival, and adverse reactions. Patients were followed for 24 mo from first administration of tomostrocel. Median follow-up since the last HSCT was 26.9 mo (range 2.4 to 63.2 mo). aGvHD was mostly severe (4, 37, and 55% grade II, III, and IV, respectively), and a median of three (reported range 0 to 10) prior therapeutic lines had been exhausted, including ruxolitinib in 75% of patients. The predominant site of aGvHD was the lower gastrointestinal tract (30%/52% with Stage 3/4). The overall response rate in this heavily pretreated cohort at Day 28 was 45% (95% confidence interval [CI] 40% to 51%). Probability of overall survival (OS) at 6, 12, and 24 mo was 44% (95% CI 38% to 49%), 33% (95% CI 27% to 38%), and 28% (95% CI 23% to 34%), respectively (median 4.3 mo). Several subgroup analyses suggested signs of efficacy compared to expected outcomes according to the literature. The safety profile of tomostrocel was favorable, consistent with previous reports. This real-world data analysis showed several efficacy signals and a reassuring safety profile for tomostrocel in multi-refractory aGvHD. Response on Day 28 was predictive for OS, regardless of prior exposure to ruxolitinib. Despite the inherent limitations associated with real-world data collection, these findings suggest that tomostrocel represents a promising treatment option for heavily pretreated and severely ill steroid-refractory aGvHD patients. Results of the ongoing randomized controlled trials are eagerly awaited.
SN - 2666-6367
ER -