Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products

Makoto Murata ^{1 , *} and Takanori Teshima ²

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MSC Therapy With Temcell for Acute GVHD

More recently, real-world outcomes for 381 patients who received Temcell as a health insurance-covered treatment for acute GVHD were reported from Japan (13). The main results of the study are summarized in Table 1. Of the 309 patients, 56% achieved OR on day 28. Of the 153 patients who received Temcell as a second-line therapy following first-line steroid therapy for classic acute GVHD, 61% achieved OR on day 28. Thus, the treatment of acute GVHD with Temcell covered by health insurance in Japan achieved an efficacy equivalent to that obtained in prospective studies of remestemcel-L with strict eligibility criteria.

On multivariate analysis, liver involvement of acute GVHD and longer duration from first-line steroid therapy to second-line MSC therapy (≥14 days vs. <14 days) were associated with a lower OR rate. Older patient (18 to 49 years and ≥50 years vs. <18 years), higher grade of GVHD (III and IV vs. ≤II), higher number of GVHD therapies before MSC therapy (≥2 vs. ≤1), and non-achievement of OR on day 28 were associated with a higher NRM. OS was significantly higher in patients with an OR on day 28 than in those without an OR.

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Conclusion

It is known that the incidence of severe acute GVHD is lower in Japanese than Caucasian patients (78), but the outcome of SR-aGVHD seems to be equally poor (4). Thus, effective second-line treatments for SR-aGVHD are an unmet need. Ruxolitinib is widely used as an acute GVHD treatment in the United States and Europe, but the use of MSCs has not been approved as a health insurance treatment in those countries. In contrast, Temcell is widely used in Japan, but ruxolitinib remains under review. Thus, it is currently impossible to compare the efficacy of remestemcel-L/Temcell and ruxolitinib in a real-world setting. As described in an earlier section, there has been a randomized, prospective study of remestemcel-L and placebo (11). The correct interpretation of the study is that the addition of remestemcel-L to another second-line therapy was not superior to a second-line therapy without remestemcel-L. In other words, the efficacy of remestemcel-L alone has not been prospectively compared with other immunosuppressive drugs in the treatment of acute GVHD.

In conclusion, the appropriate use of remestemcel-L/Temcell for acute GVHD remains to be determined. Future study is needed to establish more precisely the position of remestemcel-L/Temcell in the treatment of acute GVHD.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417106/


About the author:

Makoto Murata MD PhD was also involved in the clinical development of Temcell.
https://www.sciencedirect.com/science/article/pii/S0006497119728249