Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial

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Purpose: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. Experimental Design: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm3 injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models. Results: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Longterm safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00-0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [-10.1 (-18.1 to -2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC. Conclusions:Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted.

TidsskriftClinical Cancer Research
Udgave nummer13
Sider (fra-til)2-2897
Antal sider2.896
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
C.D. Lynggaard reports grants from Candys Foundation during the conduct of the study. C.D. Lynggaard, C. Grønhøj, and C. von Buchwald are co-inventors on patent PCT/EP2020/053878; the patent is owned by Rigshospitalet, Copenhagen University Hospital and the University of Copenhagen. A. Fischer-Nielsen is employee and shareholder of StemMedical A/S, a biotech company working with cell-enriched fat grafting. C. Grønhøj reports a patent for 5281-0127/18-7000 pending. L. Specht reports personal fees from Takeda, Kyowa Kirin, and MSD; grants from Varian, ViewRay, and Danish Cancer Society; and other support from Springer Verlag and Munksgaard Publishing outside the submitted work. No disclosures were reported by the other authors.

Funding Information:
This study was supported by the non-profit organization Candys Foundation (C.D. Lynggaard and C. Grønhøj). Section for Biostatistics and Evidence-Based Research, the Parker Institute is supported by a core grant from the Oak Foundation, a non-profit foundation (grant OCAY-18-774-OFIL). The funders of the study had no role in the design of the study, data collection, analysis, interpretation of the data, or

Publisher Copyright:
© 2022 The Authors.

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