A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases

Danielle K. DePalo; Michelle M. Dugan; Syeda Mahrukh Hussnain Naqvi; David W. Ollila; Tina J. Hieken; Matthew S. Block; Winan J. van Houdt; Michel W.J.M. Wouters; Sophie J.M. Reijers; Nethanel Asher; Kristy K. Broman; Zoey Duncan; Matilda Anderson; David E. Gyorki; Hayden Snow; Jenny Held; Jeffrey M. Farma; John T. Vetto; Jane Y.C. Hui; Madison Kolbow; Robyn P.M. Saw; Serigne N. Lo; Georgina V. Long; John F. Thompson; Youngchul Kim; Lilit Karapetyan; Lars Ny; Alexander C.J. van Akkooi; Roger Olofsson Bagge; Jonathan S. Zager

doi:10.1002/cncr.35636

A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases

Danielle K. DePalo, Michelle M. Dugan, Syeda Mahrukh Hussnain Naqvi, David W. Ollila, Tina J. Hieken, Matthew S. Block, Winan J. van Houdt, Michel W.J.M. Wouters, Sophie J.M. Reijers, Nethanel Asher, Kristy K. Broman, Zoey Duncan, Matilda Anderson, David E. Gyorki, Hayden Snow, Jenny Held, Jeffrey M. Farma, John T. Vetto, Jane Y.C. Hui, Madison KolbowRobyn P.M. Saw, Serigne N. Lo, Georgina V. Long, John F. Thompson, Youngchul Kim, Lilit Karapetyan, Lars Ny, Alexander C.J. van Akkooi, Roger Olofsson Bagge, Jonathan S. Zager

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

Abstract

BACKGROUND: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.

METHODS: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.

RESULTS: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.

CONCLUSIONS: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.

Original language	English
Article number	e35636
Pages (from-to)	e35636
Journal	Cancer
Volume	131
Issue number	1
Early online date	Oct 10 2024
DOIs	https://doi.org/10.1002/cncr.35636
State	Published - Jan 1 2025

Keywords

immune checkpoint inhibitors
in-transit metastasis
intralesional therapy
isolated limb infusion
isolated limb perfusion
metastatic melanoma
regional chemotherapy
talimogene laherparepvec
Humans
Middle Aged
Chemotherapy, Cancer, Regional Perfusion/methods
Male
Extremities/pathology
Herpesvirus 1, Human
Neoplasm Metastasis
Melanoma/drug therapy
Aged, 80 and over
Biological Products
Female
Adult
Aged
Retrospective Studies
Immune Checkpoint Inhibitors/administration & dosage
Skin Neoplasms/drug therapy

UN SDGs

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

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10.1002/cncr.35636

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DePalo, D. K., Dugan, M. M., Naqvi, S. M. H., Ollila, D. W., Hieken, T. J., Block, M. S., van Houdt, W. J., Wouters, M. W. J. M., Reijers, S. J. M., Asher, N., Broman, K. K., Duncan, Z., Anderson, M., Gyorki, D. E., Snow, H., Held, J., Farma, J. M., Vetto, J. T., Hui, J. Y. C., ... Zager, J. S. (2025). A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases. Cancer, 131(1), e35636. Article e35636. https://doi.org/10.1002/cncr.35636

@article{b365741b51a946e0acf0067a2b853ae5,

title = "A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases",

abstract = "BACKGROUND: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.METHODS: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.RESULTS: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.CONCLUSIONS: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.",

keywords = "immune checkpoint inhibitors, in-transit metastasis, intralesional therapy, isolated limb infusion, isolated limb perfusion, metastatic melanoma, regional chemotherapy, talimogene laherparepvec, Humans, Middle Aged, Chemotherapy, Cancer, Regional Perfusion/methods, Male, Extremities/pathology, Herpesvirus 1, Human, Neoplasm Metastasis, Melanoma/drug therapy, Aged, 80 and over, Biological Products, Female, Adult, Aged, Retrospective Studies, Immune Checkpoint Inhibitors/administration & dosage, Skin Neoplasms/drug therapy",

author = "DePalo, {Danielle K.} and Dugan, {Michelle M.} and Naqvi, {Syeda Mahrukh Hussnain} and Ollila, {David W.} and Hieken, {Tina J.} and Block, {Matthew S.} and {van Houdt}, {Winan J.} and Wouters, {Michel W.J.M.} and Reijers, {Sophie J.M.} and Nethanel Asher and Broman, {Kristy K.} and Zoey Duncan and Matilda Anderson and Gyorki, {David E.} and Hayden Snow and Jenny Held and Farma, {Jeffrey M.} and Vetto, {John T.} and Hui, {Jane Y.C.} and Madison Kolbow and Saw, {Robyn P.M.} and Lo, {Serigne N.} and Long, {Georgina V.} and Thompson, {John F.} and Youngchul Kim and Lilit Karapetyan and Lars Ny and {van Akkooi}, {Alexander C.J.} and Bagge, {Roger Olofsson} and Zager, {Jonathan S.}",

note = "{\textcopyright} 2024 American Cancer Society.",

year = "2025",

month = jan,

day = "1",

doi = "10.1002/cncr.35636",

language = "English",

volume = "131",

pages = "e35636",

journal = "Cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "1",

}

DePalo, DK, Dugan, MM, Naqvi, SMH, Ollila, DW, Hieken, TJ, Block, MS, van Houdt, WJ, Wouters, MWJM, Reijers, SJM, Asher, N, Broman, KK, Duncan, Z, Anderson, M, Gyorki, DE, Snow, H, Held, J, Farma, JM, Vetto, JT, Hui, JYC, Kolbow, M, Saw, RPM, Lo, SN, Long, GV, Thompson, JF, Kim, Y, Karapetyan, L, Ny, L, van Akkooi, ACJ, Bagge, RO & Zager, JS 2025, 'A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases', Cancer, vol. 131, no. 1, e35636, pp. e35636. https://doi.org/10.1002/cncr.35636

A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases. / DePalo, Danielle K.; Dugan, Michelle M.; Naqvi, Syeda Mahrukh Hussnain et al.
In: Cancer, Vol. 131, No. 1, e35636, 01.01.2025, p. e35636.

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

TY - JOUR

T1 - A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases

AU - DePalo, Danielle K.

AU - Dugan, Michelle M.

AU - Naqvi, Syeda Mahrukh Hussnain

AU - Ollila, David W.

AU - Hieken, Tina J.

AU - Block, Matthew S.

AU - van Houdt, Winan J.

AU - Wouters, Michel W.J.M.

AU - Reijers, Sophie J.M.

AU - Asher, Nethanel

AU - Broman, Kristy K.

AU - Duncan, Zoey

AU - Anderson, Matilda

AU - Gyorki, David E.

AU - Snow, Hayden

AU - Held, Jenny

AU - Farma, Jeffrey M.

AU - Vetto, John T.

AU - Hui, Jane Y.C.

AU - Kolbow, Madison

AU - Saw, Robyn P.M.

AU - Lo, Serigne N.

AU - Long, Georgina V.

AU - Thompson, John F.

AU - Kim, Youngchul

AU - Karapetyan, Lilit

AU - Ny, Lars

AU - van Akkooi, Alexander C.J.

AU - Bagge, Roger Olofsson

AU - Zager, Jonathan S.

PY - 2025/1/1

Y1 - 2025/1/1

N2 - BACKGROUND: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.METHODS: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.RESULTS: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.CONCLUSIONS: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.

AB - BACKGROUND: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC.METHODS: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM.RESULTS: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D.CONCLUSIONS: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.

KW - immune checkpoint inhibitors

KW - in-transit metastasis

KW - intralesional therapy

KW - isolated limb infusion

KW - isolated limb perfusion

KW - metastatic melanoma

KW - regional chemotherapy

KW - talimogene laherparepvec

KW - Humans

KW - Middle Aged

KW - Chemotherapy, Cancer, Regional Perfusion/methods

KW - Male

KW - Extremities/pathology

KW - Herpesvirus 1, Human

KW - Neoplasm Metastasis

KW - Melanoma/drug therapy

KW - Aged, 80 and over

KW - Biological Products

KW - Female

KW - Adult

KW - Aged

KW - Retrospective Studies

KW - Immune Checkpoint Inhibitors/administration & dosage

KW - Skin Neoplasms/drug therapy

UR - http://www.scopus.com/inward/record.url?scp=85208543488&partnerID=8YFLogxK

U2 - 10.1002/cncr.35636

DO - 10.1002/cncr.35636

M3 - Article

C2 - 39522025

AN - SCOPUS:85208543488

SN - 0008-543X

VL - 131

SP - e35636

JO - Cancer

JF - Cancer

IS - 1

M1 - e35636

ER -

A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases

Abstract

Keywords

UN SDGs

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Data from H. Lee Moffitt Cancer Center and Research Institute Provide New Insights into Melanoma (A Comparison of Isolated Limb Infusion/perfusion, Immune Checkpoint Inhibitors, and Intralesional Therapy As First-line Treatment for Patients ...)

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A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases

Abstract

Keywords

UN SDGs

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Data from H. Lee Moffitt Cancer Center and Research Institute Provide New Insights into Melanoma (A Comparison of Isolated Limb Infusion/perfusion, Immune Checkpoint Inhibitors, and Intralesional Therapy As First-line Treatment for Patients ...)

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