학술논문
Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease
Document Type
Report
Author
Bonig, Halvard; Verbeek, Mareike; Herhaus, Peter; Braitssch, Krischan; Beutel, Gernot; Schmid, Christoph; Müller, Nadine; Bug, Gesine; Döring, Michaela; von Stackelberg, Arend; Tischer, Johanna; Ayuk, Francis; Wulf, Gerald; Holtick, Udo; Pfeffermann, Lisa-Marie; Jahrsdörfer, Bernd; Schrezenmeier, Hubert; Kuci, Selim; Kuci, Zyrafete; Zens, Anke; Tribanek, Michael; Zeiser, Robert; Huenecke, Sabine; Bader, Peter
Source
Journal of Translational Medicine. November 21, 2023, Vol. 21 Issue 1
Subject
Language
English
ISSN
1479-5876
Abstract
Author(s): Halvard Bonig[sup.1,2,3] , Mareike Verbeek[sup.4] , Peter Herhaus[sup.4] , Krischan Braitssch[sup.4] , Gernot Beutel[sup.5] , Christoph Schmid[sup.6] , Nadine Müller[sup.7] , Gesine Bug[sup.8] , Michaela Döring[sup.9] , Arend von [...]
Background Patients with steroid-refractory acute graft-versus-host disease (aGvHD) not tolerating/responding to ruxolitinib (RR-aGvHD) have a dismal prognosis. Methods We retrospectively assessed real-world outcomes of RR-aGvHD treated with the random-donor allogeneic MSC preparation MSC-FFM, available via Hospital Exemption in Germany. MSC-FFM is provided as frozen cell dispersion for administration as i.v. infusion immediately after thawing, at a recommended dose of 1-2 million MSCs/kg body weight in 4 once-weekly doses. 156 patients, 33 thereof children, received MSC-FFM; 5% had Grade II, 40% had Grade III, and 54% had Grade IV aGvHD. Median (range) number of prior therapies was 4 (1-10) in adults and 7 (2-11) in children. Results The safety profile of MSC-FFM was consistent with previous reports for MSC therapies in general and MSC-FFM specifically. The overall response rate at Day 28 was 46% (95% confidence interval [CI] 36-55%) in adults and 64% (45-80%) in children; most responses were durable. Probability of overall survival at 6, 12 and 24 months was 47% (38-56%), 35% (27-44%) and 30% (22-39%) for adults, and 59% (40-74%), 42% (24-58%) and 35% (19-53%) for children, respectively (whole cohort: median OS 5.8 months). Conclusion A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, respectively (median 28 days). Our data thus suggest effectiveness of MSC-FFM in RR-aGvHD. Keywords: MSC-FFM, Mesenchymal stromal cells, Steroid-refractory, Ruxolitinib-refractory, Allogeneic haematopoietic stem cell transplantation
Background Patients with steroid-refractory acute graft-versus-host disease (aGvHD) not tolerating/responding to ruxolitinib (RR-aGvHD) have a dismal prognosis. Methods We retrospectively assessed real-world outcomes of RR-aGvHD treated with the random-donor allogeneic MSC preparation MSC-FFM, available via Hospital Exemption in Germany. MSC-FFM is provided as frozen cell dispersion for administration as i.v. infusion immediately after thawing, at a recommended dose of 1-2 million MSCs/kg body weight in 4 once-weekly doses. 156 patients, 33 thereof children, received MSC-FFM; 5% had Grade II, 40% had Grade III, and 54% had Grade IV aGvHD. Median (range) number of prior therapies was 4 (1-10) in adults and 7 (2-11) in children. Results The safety profile of MSC-FFM was consistent with previous reports for MSC therapies in general and MSC-FFM specifically. The overall response rate at Day 28 was 46% (95% confidence interval [CI] 36-55%) in adults and 64% (45-80%) in children; most responses were durable. Probability of overall survival at 6, 12 and 24 months was 47% (38-56%), 35% (27-44%) and 30% (22-39%) for adults, and 59% (40-74%), 42% (24-58%) and 35% (19-53%) for children, respectively (whole cohort: median OS 5.8 months). Conclusion A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, respectively (median 28 days). Our data thus suggest effectiveness of MSC-FFM in RR-aGvHD. Keywords: MSC-FFM, Mesenchymal stromal cells, Steroid-refractory, Ruxolitinib-refractory, Allogeneic haematopoietic stem cell transplantation