Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)

Charlotte Duch Lynggaard; Christian Grønhøj; Robin Christensen; Anne Fischer-Nielsen; Jacob Melchiors; Lena Specht; Elo Andersen; Jann Mortensen; Peter Sandor Oturai; Gry Hoffmann Barfod; Eva Kannik Haastrup; Michael Møller-Hansen; Mandana Haack-Sørensen; Annette Ekblond; Jens Kastrup; Siri Beier Jensen; Christian von Buchwald

doi:10.1093/stcltm/szac011

Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)

Charlotte Duch Lynggaard^*, Christian Grønhøj, Robin Christensen, Anne Fischer-Nielsen, Jacob Melchiors, Lena Specht, Elo Andersen, Jann Mortensen, Peter Sandor Oturai, Gry Hoffmann Barfod, Eva Kannik Haastrup, Michael Møller-Hansen, Mandana Haack-Sørensen, Annette Ekblond, Jens Kastrup, Siri Beier Jensen, Christian von Buchwald

^*Corresponding author for this work

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Abstract

No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC) - xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P =. 0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P =. 017) mL/minute. XQ summary score decreased by 22.6 units (P =. 0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P =. 0013), sticky saliva 23.3 (P =. 0015), and swallowing 10.0 (P =. 0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.

Original language	English
Journal	Stem Cells Translational Medicine
Volume	11
Issue	5
Pages (from-to)	478-489
Number of pages	12
ISSN	2157-6564
DOIs	https://doi.org/10.1093/stcltm/szac011
Publication status	Published - May 2022

Keywords

HEAD
IMPACT
LIFE
MECHANISMS
SALIVARY
cancer
clinical trials
mesenchymal stem cells
stem cells
xerostomia

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szac011Final published version, 4.9 MBLicence: CC BY

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Lynggaard, C. D., Grønhøj, C., Christensen, R., Fischer-Nielsen, A., Melchiors, J., Specht, L., Andersen, E., Mortensen, J., Oturai, P. S., Barfod, G. H., Haastrup, E. K., Møller-Hansen, M., Haack-Sørensen, M., Ekblond, A., Kastrup, J., Jensen, S. B., & von Buchwald, C. (2022). Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II). Stem Cells Translational Medicine, 11(5), 478-489. https://doi.org/10.1093/stcltm/szac011

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title = "Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)",

abstract = "No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC) - xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P =. 0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P =. 017) mL/minute. XQ summary score decreased by 22.6 units (P =. 0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P =. 0013), sticky saliva 23.3 (P =. 0015), and swallowing 10.0 (P =. 0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.",

keywords = "HEAD, IMPACT, LIFE, MECHANISMS, SALIVARY, cancer, clinical trials, mesenchymal stem cells, stem cells, xerostomia",

author = "Lynggaard, {Charlotte Duch} and Christian Gr{\o}nh{\o}j and Robin Christensen and Anne Fischer-Nielsen and Jacob Melchiors and Lena Specht and Elo Andersen and Jann Mortensen and Oturai, {Peter Sandor} and Barfod, {Gry Hoffmann} and Haastrup, {Eva Kannik} and Michael M{\o}ller-Hansen and Mandana Haack-S{\o}rensen and Annette Ekblond and Jens Kastrup and Jensen, {Siri Beier} and {von Buchwald}, Christian",

year = "2022",

month = may,

doi = "10.1093/stcltm/szac011",

language = "English",

volume = "11",

pages = "478--489",

journal = "Stem Cells Translational Medicine",

issn = "2157-6564",

publisher = "Oxford University Press",

number = "5",

}

Lynggaard, CD, Grønhøj, C, Christensen, R, Fischer-Nielsen, A, Melchiors, J, Specht, L, Andersen, E, Mortensen, J, Oturai, PS, Barfod, GH, Haastrup, EK, Møller-Hansen, M, Haack-Sørensen, M, Ekblond, A, Kastrup, J, Jensen, SB & von Buchwald, C 2022, 'Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)', Stem Cells Translational Medicine, vol. 11, no. 5, pp. 478-489. https://doi.org/10.1093/stcltm/szac011

Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II). / Lynggaard, Charlotte Duch; Grønhøj, Christian; Christensen, Robin et al.
In: Stem Cells Translational Medicine, Vol. 11, No. 5, 05.2022, p. 478-489.

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

TY - JOUR

T1 - Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia

T2 - A Safety Study (MESRIX-II)

AU - Lynggaard, Charlotte Duch

AU - Grønhøj, Christian

AU - Christensen, Robin

AU - Fischer-Nielsen, Anne

AU - Melchiors, Jacob

AU - Specht, Lena

AU - Andersen, Elo

AU - Mortensen, Jann

AU - Oturai, Peter Sandor

AU - Barfod, Gry Hoffmann

AU - Haastrup, Eva Kannik

AU - Møller-Hansen, Michael

AU - Haack-Sørensen, Mandana

AU - Ekblond, Annette

AU - Kastrup, Jens

AU - Jensen, Siri Beier

AU - von Buchwald, Christian

PY - 2022/5

Y1 - 2022/5

N2 - No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC) - xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P =. 0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P =. 017) mL/minute. XQ summary score decreased by 22.6 units (P =. 0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P =. 0013), sticky saliva 23.3 (P =. 0015), and swallowing 10.0 (P =. 0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.

AB - No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC) - xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P =. 0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P =. 017) mL/minute. XQ summary score decreased by 22.6 units (P =. 0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P =. 0013), sticky saliva 23.3 (P =. 0015), and swallowing 10.0 (P =. 0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.

KW - HEAD

KW - IMPACT

KW - LIFE

KW - MECHANISMS

KW - SALIVARY

KW - cancer

KW - clinical trials

KW - mesenchymal stem cells

KW - stem cells

KW - xerostomia

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U2 - 10.1093/stcltm/szac011

DO - 10.1093/stcltm/szac011

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SN - 2157-6564

VL - 11

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EP - 489

JO - Stem Cells Translational Medicine

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IS - 5

ER -

Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)

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Keywords

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