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

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

doi:10.1158/1078-0432.CCR-21-4520

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

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

^*Corresponding author for this work

Department of Dentistry and Oral Health - Institutledelsen, Odontologi og Oral Sundhed

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

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 language	English
Journal	Clinical Cancer Research
Volume	28
Issue	13
Pages (from-to)	2890–2897
Number of pages	8
ISSN	1078-0432
DOIs	https://doi.org/10.1158/1078-0432.CCR-21-4520
Publication status	Published - Jul 2022

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Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced XerostomiaFinal published version, 591 KBLicence: CC BY-NC-ND

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Lynggaard, C. D., Grønhøj, C., Jensen, S. B., Christensen, R., Specht, L., Andersen, E., Andersen, T. T., Ciochon, U. M., Rathje, G. S., Hansen, A. E., Stampe, H., Fischer-Nielsen, A., & Von Buchwald, C. (2022). 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. Clinical Cancer Research, 28(13), 2890–2897. https://doi.org/10.1158/1078-0432.CCR-21-4520

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title = "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",

abstract = "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.",

author = "Lynggaard, {Charlotte Duch} and Christian Gr{\o}nh{\o}j and Jensen, {Siri B.} and Robin Christensen and Lena Specht and Elo Andersen and Andersen, {Tobias T.} and Ciochon, {Urszula M.} and Rathje, {Gulla S.} and Hansen, {Adam E.} and Helene Stampe and Anne Fischer-Nielsen and {Von Buchwald}, Christian",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

month = jul,

doi = "10.1158/1078-0432.CCR-21-4520",

language = "English",

volume = "28",

pages = "2890–2897",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "13",

}

Lynggaard, CD, Grønhøj, C, Jensen, SB, Christensen, R, Specht, L, Andersen, E, Andersen, TT, Ciochon, UM, Rathje, GS, Hansen, AE, Stampe, H, Fischer-Nielsen, A & Von Buchwald, C 2022, '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', Clinical Cancer Research, vol. 28, no. 13, pp. 2890–2897. https://doi.org/10.1158/1078-0432.CCR-21-4520

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. / Lynggaard, Charlotte Duch; Grønhøj, Christian; Jensen, Siri B. et al.
In: Clinical Cancer Research, Vol. 28, No. 13, 07.2022, p. 2890–2897.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia

T2 - Primary Results of the MESRIX Phase I/II Randomized Trial

AU - Lynggaard, Charlotte Duch

AU - Grønhøj, Christian

AU - Jensen, Siri B.

AU - Christensen, Robin

AU - Specht, Lena

AU - Andersen, Elo

AU - Andersen, Tobias T.

AU - Ciochon, Urszula M.

AU - Rathje, Gulla S.

AU - Hansen, Adam E.

AU - Stampe, Helene

AU - Fischer-Nielsen, Anne

AU - Von Buchwald, Christian

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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.

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U2 - 10.1158/1078-0432.CCR-21-4520

DO - 10.1158/1078-0432.CCR-21-4520

M3 - Journal article

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AN - SCOPUS:85133384467

SN - 1078-0432

VL - 28

SP - 2890

EP - 2897

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 13

ER -

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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