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. 2023 Nov 21;21(1):837.
doi: 10.1186/s12967-023-04731-1.

Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease

Halvard Bonig  1   2   3 , Mareike Verbeek  4 , Peter Herhaus  4 , Krischan Braitsch  4 , Gernot Beutel  5 , Christoph Schmid  6 , Nadine Müller  7 , Gesine Bug  8 , Michaela Döring  9 , Arend von Stackelberg  10 , Johanna Tischer  11 , Francis Ayuk  12 , Gerald Wulf  13 , Udo Holtick  14 , Lisa-Marie Pfeffermann  2 , Bernd Jahrsdörfer  15 , Hubert Schrezenmeier  15 , Selim Kuci  16 , Zyrafete Kuci  16 , Anke Zens  17 , Michael Tribanek  17 , Robert Zeiser  18 , Sabine Huenecke  19 , Peter Bader  20
Affiliations

Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease

Halvard Bonig et al. J Transl Med. .

Erratum in

Abstract

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: Allogeneic haematopoietic stem cell transplantation; MSC-FFM; Mesenchymal stromal cells; Ruxolitinib-refractory; Steroid-refractory.

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Conflict of interest statement

PB, SK, ZK, and HB have received licensing fees and royalties for MSC-FFM. HB furthermore acknowledges research support from Erydel, Miltenyi, Sandoz-Hexal (a Novartis company); honoraria and speaker fees from Medac, Miltenyi, Novartis and Terumo BCT; consultancy and membership in advisory boards for Boehringer-Ingelheim, Celgene (a BMS company), Medac, Novartis and Sandoz-Hexal; stock ownership in Healthineers. MV declares honoraria from Pfizer, Novartis, Jazz, MSD and Abbvie; travel support from medac, Jazz and Gilead, advisory board in MSD and Abbvie. AZ and MT are employees of medac, licensee of MSC-FFM. RZ is the Principal Investigator of the IDUNN trial and was the Principal Investigator of several ruxolitinib trials, including the pivotal REACH2 study. RZ received speaker fees from Novartis, Incyte, MNK and Sanofi. GB has received honoraria from Novartis, Jazz, BMS, Gilead and Pfizer and travel grants from Jazz, Gilead and Neovii. None of the other authors have any declarations.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves for overall survival in patients with RR-aGvHD. Curves indicate overall survival (OS) for children (blue) and adults (red) with ruxolitinib-refractory acute graft-versus-host disease treated with MSC-FFM
See this image and copyright information in PMC

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