REAL-WORLD DATA SUGGEST EFFECTIVNESS OF THE ALLOGENEIC MESENCHYMAL STROMAL CELLS PREPARATION MSC-FFM IN RUXOLITINIB-REFRACTORY OR -INTOLERANT ACUTE GRAFT-VERSUS-HOST DISEASE

• Published in: Cytotherapy (Oxford, England) Vol. 26; no. 6; p. S24
• Main Authors: Pfeffermann, L., Boenig, H.B., Verbeek, M., Herhaus, P., Braitsch, K., Beutel, G., Schmid, C., Muller, N., Bug, G., Döring, M., von Stackelberg, A., Tischer, J., Ayuk, F., Wulf, G., Holtick, U., Jahrsdorfer, B., Schrezenmeier, H., Kuci, S., Kuci, Z., Zens, A., Tribanek, M., Zeiser, R., Huenecke, S., Bader, P.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.06.2024
• Subjects: aGvHD; MSC; Ruxolitinib; aGvHD; MSC; Ruxolitinib
• DOI: 10.1016/j.jcyt.2024.03.038
• ISSN: 1465-3249

Acute graft-versus-host disease (aGvHD) remains the leading cause of treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Current first-line treatment of aGvHD is with high-dose corticosteroids. The standard for steroid-refractory aGvHD (SR-aGvHD) is the Janus kinase inhibitor ruxolitinib. Outcomes for patients with ruxolitinib-refractory or -intolerant aGvHD (RR-aGvHD) are poor. In a recent real-world study of adult patients with RR-aGvHD (Abedin Br J Haematol 2021 Nov;195(3):429-432.) median survival was 28 days, and the probabilities of overall survival (OS) at 6, 12, and 24 months were 20%, 16%, and 10%, respectively. We assessed real-world outcomes of patients with RR-aGvHD treated with the random-donor allogeneic MSC preparation MSC-FFM available via Hospital Exemption in Germany. Between December 2017 and February 2023, 156 patients, 33 children and adolescents and 123 adults, received MSC-FFM for RR-aGvHD. Overall, 32 German sites contributed 139 patients, while the remaining patients came from France, Hungary, Norway, Sweden, and Switzerland. MSC-FFM is manufactured from pooled bone marrow mononuclear cells from eight HLA-disparate healthy donors. MSCs are selected by plastic adherence, expanded in platelet lysate-enriched media in 2D culture until the end of passage 3, then frozen in saline-albumin with DMSO. Manufacturing is according to GMP and all applicable laws and regulations. The recommended dosing for MSC-FFM is 1-2x106 cells/kg body weight (BW), for four weekly doses. The median dose administered was 1.18x106 cells/kg BW, with a median number of four doses and a median inter-dose interval of 7 days. Tolerability of MSC-FFM was good, with only five adverse drug reactions reported in three adult patients, which did not result in cessation of MSC treatment or dose reductions. The overall response rate (ORR) at day +28 after the first dose was 49%, with 45% in adults and 64% in children. Most responses were durable, resulting in an ORR of 49% for both adults and children at 2 months, and 40% at 6 months after start of treatment. OS at 6, 12, and 24 months was 47%, 35%, and 30% for adults, and 59%, 42%, and 35% for children, respectively. After a median follow-up of 26.7 month, median OS was 5.8 months. These outcomes compare favourably to published OS estimates for adult RR-aGvHD patients not treated with MSC-FFM (Abedin BJH). The unique MSC-preparation MSC-FFM appears to be effective against RR-aGvHD.