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
Year: 2026
Type: article
Study design: Observational Study
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.
Authors: Mareike Verbeek, Halvard Bonig, Francis Ayuk, Gesine Bug, Maud D’Aveni-Piney, Daniela Heidenreich, Peter Herhaus, Udo Holtick, Igor Kos, William Krüger, Maria Teresa Lupo-Stanghellini, Thomas Mika, Charlotte Neuerburg, Elena Osswald, Victoria Panagiota, Christian Reicherts, Christoph Schmid, Micha Srour, Friedrich Stölzel, Michael Tribanek, Friederike Wortmann, Gerald Wulf, Anke Zens, Robert Zeiser
Institutions: Technical University of Munich, Goethe University Frankfurt, University Medical Center Hamburg-Eppendorf, University Hospital Frankfurt, University Medical Centre Mannheim, University of Cologne, University Hospital Cologne, Universitätsklinikum des Saarlandes, Universitätsmedizin Greifswald, IRCCS Ospedale San Raffaele, Universitätsklinikum Knappschaftskrankenhaus Bochum, University Hospital Bonn, Medac (Germany), Medizinische Hochschule Hannover, University Hospital Münster, University Hospital Augsburg, Centre Hospitalier Universitaire de Lille, University Hospital Schleswig-Holstein, Universitätsmedizin Göttingen, University Medical Center Freiburg
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W7212383139