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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  • Charlotte Duch Lynggaard, University of Copenhagen
  • ,
  • Christian Grønhøj, University of Copenhagen
  • ,
  • Siri B. Jensen
  • Robin Christensen, University of Copenhagen, University of Southern Denmark
  • ,
  • Lena Specht, University of Copenhagen
  • ,
  • Elo Andersen, University of Copenhagen
  • ,
  • Tobias T. Andersen, University of Copenhagen
  • ,
  • Urszula M. Ciochon, University of Copenhagen
  • ,
  • Gulla S. Rathje, University of Copenhagen
  • ,
  • Adam E. Hansen, University of Copenhagen
  • ,
  • Helene Stampe, University of Copenhagen
  • ,
  • Anne Fischer-Nielsen, University of Copenhagen
  • ,
  • Christian Von Buchwald, University of Copenhagen

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.

Original languageEnglish
JournalClinical Cancer Research
Volume28
Issue13
Pages (from-to)2890–2897
Number of pages8
ISSN1078-0432
DOIs
Publication statusPublished - Jul 2022

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