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. 2024 Jun;30(6):1556-1558.
doi: 10.1038/s41591-024-02990-z. Epub 2024 May 22.

Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease

Kilian Kelly  1 , Adrian J C Bloor  2 , James E Griffin  3 , Rohini Radia  4 , David T Yeung  5   6 , John E J Rasko  7   8   9
Affiliations

Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease

Kilian Kelly et al. Nat Med. 2024 Jun.

Abstract

The first completed clinical trial of induced pluripotent stem cell (iPS cell)-derived cells was conducted in 15 participants with steroid-resistant acute graft-versus-host disease. After intravenous infusion of mesenchymal stromal cells (CYP-001 derived from a clone of human iPS cells), we reported the safety, tolerability and efficacy within the primary evaluation period at day 100. We now report results at the 2-year follow-up: 9 of 15 (60%) participants survived, which compares favorably with previously reported outcomes in studies of steroid-resistant acute graft-versus-host disease. Causes of death were complications commonly observed in recipients of allogeneic hematopoietic stem cell transplantation, and not considered by the investigators to be related to CYP-001 treatment. There were no serious adverse events, tumors or other safety concerns related to CYP-001. In conclusion, systemic delivery of iPS cell-derived cells was safe and well tolerated over 2 years of follow-up, with sustained outcomes up to 2 years after the first infusion. ClinicalTrials.gov registration: NCT02923375 .

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Conflict of interest statement

K.K. is an employee and shareholder of Cynata Therapeutics, which funded the work described in this manuscript. D.T.Y. reports honoraria and research funding from Novartis. J.E.J.R. holds shares in Rarecyte and Woke Pharmaceuticals; reports data safety and monitoring board membership for the Fanconi anemia trial; has received grant and research support from the National Health and Medical Research Council (Investigator Grant), Cancer Council New South Wales, the Cancer Institute of New South Wales, the Medical Research Future Fund, Therapeutic Innovation Australia and philanthropic foundations; reports supply of material (via a material transfer agreement) or consultancy or honoraria from Rarecyte, Novartis, bluebird bio, Spark Therapeutics, Cynata Therapeutics, Pfizer and CRISPR Therapeutics; he reports membership on an entity’s board of directors or advisory committees as co-founder of AAVec Bio and nonexecutive director of Kennerton Capital; and is employed by the Sydney Local Health District at Royal Prince Alfred Hospital as Head of the Department of Cell & Molecular Therapies. A.J.C.B., J.E.G. and R.R. declare no competing interests.

Figures

Fig. 1
Fig. 1. Kaplan–Meier survival curve.
Letters represent cause of death: G, GvHD; P, pneumonia; S, sepsis/multi-organ dysfunction; R, relapse. Source data
See this image and copyright information in PMC

References

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