Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Ida Maria Leppäpuska; Pauliina Hartiala; Sinikka Suominen; Erkki Suominen; Ilkka Kaartinen; Maija Mäki; Marko Seppänen; Juha Kiiski; Tiina Viitanen; Outi Lahdenperä; Antti Vuolanto; Kari Alitalo; Anne M. Saarikko

doi:10.1016/j.bjps.2022.08.011

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Ida Maria Leppäpuska, Pauliina Hartiala, Sinikka Suominen, Erkki Suominen, Ilkka Kaartinen, Maija Mäki, Marko Seppänen, Juha Kiiski, Tiina Viitanen, Outi Lahdenperä, Antti Vuolanto, Kari Alitalo, Anne M. Saarikko

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Abstract

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 10¹⁰ viral particles (vp)), and 12 patients received a higher dose (1 × 10¹¹ vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months’ of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

Original language	English
Pages (from-to)	3938-3945
Journal	Journal of Plastic, Reconstructive and Aesthetic Surgery
Volume	75
Issue number	11
Early online date	2022
DOIs	https://doi.org/10.1016/j.bjps.2022.08.011
Publication status	Published - Nov 2022
Publication type	A1 Journal article-refereed

Funding

PH, SS, ES, IK, TV, and AS have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland). KA has been a consultant for Herantis Pharma Plc. AV and OL are employees of Herantis Pharma Plc. (Espoo, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. We wish to thank the patients participating in this study, the study nurses, and operating room and plastic surgery ward personnel at all participating centers. Statistical assistance was provided by Eliisa Löyttyniemi (Turku, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. The research protocol was approved by the Ethical Committee of the Helsinki University Hospital. Financial Disclosure Statement. PH, SS, ES, IK, TV, and AS have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland). KA has been a consultant for Herantis Pharma Plc. AV and OL are employees of Herantis Pharma Plc. (Espoo, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript.

Keywords

BCRL
Breast cancer-related lymphedema
Breast reconstruction
Microvascular lymph node transfer
Reconstructive surgery
VEGF-C

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bjps.2022.08.011Licence: CC BY

1-s2.0-S1748681522004545-mainFinal published version, 1.23 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202301181520Licence: CC BY

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Leppäpuska, I. M., Hartiala, P., Suominen, S., Suominen, E., Kaartinen, I., Mäki, M., Seppänen, M., Kiiski, J., Viitanen, T., Lahdenperä, O., Vuolanto, A., Alitalo, K., & Saarikko, A. M. (2022). Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema. Journal of Plastic, Reconstructive and Aesthetic Surgery, 75(11), 3938-3945. https://doi.org/10.1016/j.bjps.2022.08.011

@article{b403757771a144059ee79f6ba22f0b0b,

title = "Phase 1 Lymfactin{\textregistered} Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema",

abstract = "BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin{\textregistered} is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin{\textregistered} was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin{\textregistered}, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months{\textquoteright} of follow-up, the results indicate that Lymfactin{\textregistered} is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.",

keywords = "BCRL, Breast cancer-related lymphedema, Breast reconstruction, Microvascular lymph node transfer, Reconstructive surgery, VEGF-C",

author = "Lepp{\"a}puska, {Ida Maria} and Pauliina Hartiala and Sinikka Suominen and Erkki Suominen and Ilkka Kaartinen and Maija M{\"a}ki and Marko Sepp{\"a}nen and Juha Kiiski and Tiina Viitanen and Outi Lahdenper{\"a} and Antti Vuolanto and Kari Alitalo and Saarikko, {Anne M.}",

note = "Funding Information: PH, SS, ES, IK, TV, and AS have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland). KA has been a consultant for Herantis Pharma Plc. AV and OL are employees of Herantis Pharma Plc. (Espoo, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. Funding Information: We wish to thank the patients participating in this study, the study nurses, and operating room and plastic surgery ward personnel at all participating centers. Statistical assistance was provided by Eliisa L{\"o}yttyniemi (Turku, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. The research protocol was approved by the Ethical Committee of the Helsinki University Hospital. Financial Disclosure Statement. PH, SS, ES, IK, TV, and AS have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland). KA has been a consultant for Herantis Pharma Plc. AV and OL are employees of Herantis Pharma Plc. (Espoo, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. Publisher Copyright: {\textcopyright} 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons",

year = "2022",

month = nov,

doi = "10.1016/j.bjps.2022.08.011",

language = "English",

volume = "75",

pages = "3938--3945",

journal = "Journal of Plastic, Reconstructive and Aesthetic Surgery",

issn = "1748-6815",

publisher = "Elsevier",

number = "11",

}

Leppäpuska, IM, Hartiala, P, Suominen, S, Suominen, E, Kaartinen, I, Mäki, M, Seppänen, M, Kiiski, J, Viitanen, T, Lahdenperä, O, Vuolanto, A, Alitalo, K & Saarikko, AM 2022, 'Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema', Journal of Plastic, Reconstructive and Aesthetic Surgery, vol. 75, no. 11, pp. 3938-3945. https://doi.org/10.1016/j.bjps.2022.08.011

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema. / Leppäpuska, Ida Maria; Hartiala, Pauliina; Suominen, Sinikka et al.
In: Journal of Plastic, Reconstructive and Aesthetic Surgery, Vol. 75, No. 11, 11.2022, p. 3938-3945.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Phase 1 Lymfactin® Study

T2 - 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

AU - Leppäpuska, Ida Maria

AU - Hartiala, Pauliina

AU - Suominen, Sinikka

AU - Suominen, Erkki

AU - Kaartinen, Ilkka

AU - Mäki, Maija

AU - Seppänen, Marko

AU - Kiiski, Juha

AU - Viitanen, Tiina

AU - Lahdenperä, Outi

AU - Vuolanto, Antti

AU - Alitalo, Kari

AU - Saarikko, Anne M.

N1 - Funding Information: PH, SS, ES, IK, TV, and AS have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland). KA has been a consultant for Herantis Pharma Plc. AV and OL are employees of Herantis Pharma Plc. (Espoo, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. Funding Information: We wish to thank the patients participating in this study, the study nurses, and operating room and plastic surgery ward personnel at all participating centers. Statistical assistance was provided by Eliisa Löyttyniemi (Turku, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. The research protocol was approved by the Ethical Committee of the Helsinki University Hospital. Financial Disclosure Statement. PH, SS, ES, IK, TV, and AS have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland). KA has been a consultant for Herantis Pharma Plc. AV and OL are employees of Herantis Pharma Plc. (Espoo, Finland). This trial was supported by Herantis Pharma Plc. (Espoo, Finland). The sponsor has been responsible for trial management and has also reviewed this manuscript. Publisher Copyright: © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons

PY - 2022/11

Y1 - 2022/11

N2 - BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months’ of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

AB - BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months’ of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

KW - BCRL

KW - Breast cancer-related lymphedema

KW - Breast reconstruction

KW - Microvascular lymph node transfer

KW - Reconstructive surgery

KW - VEGF-C

U2 - 10.1016/j.bjps.2022.08.011

DO - 10.1016/j.bjps.2022.08.011

M3 - Article

AN - SCOPUS:85138531535

SN - 1748-6815

VL - 75

SP - 3938

EP - 3945

JO - Journal of Plastic, Reconstructive and Aesthetic Surgery

JF - Journal of Plastic, Reconstructive and Aesthetic Surgery

IS - 11

ER -

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Abstract

Funding

Keywords

Publication forum classification

ASJC Scopus subject areas

UN SDGs

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