The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

Jane Hui

doi:10.1016/j.ejca.2022.03.041

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

Jane Hui

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

15 Scopus citations

Abstract

PurposeGuidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics.MethodsA multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions.ResultsA total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively.ConclusionSystemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

Original language	English
Pages (from-to)	210-222
Number of pages	13
Journal	European journal of cancer (Oxford, England : 1990)
Volume	169
DOIs	https://doi.org/10.1016/j.ejca.2022.03.041
State	Published - Jul 2022

Bibliographical note

Funding Information:
J Weber: Consult for Merck, Genentech, Astra Zeneca, GlaxoSmithKline, Novartis, Nektar, Celldex, Incyte, Biond, ImCheck, Sellas, Evaxion and EMD Serono. Advisory board member Bristol-Myers Squibb. Equity in Biond, Evaxion, Instil Bio and Neximmune. Scientific advisory boards for CytoMx, Incyte, ImCheck, Biond, Sellas, Instil Bio OncoC4 and Neximmune. Institutional research support from Bristol-Myers Squibb, Merck, GlaxoSmithKline, Moderna, Pfizer, Novartis and Astra Zeneca. Named on patents from Moffitt Cancer Center and Biodesix.

Funding Information:
D Ollila: Advisory boards and/or Consulting for Philogen, Merck, Novartis and Castle Biosciences. Medical Advisory Bopard - Delcath Systems. Speaker honorarium from Sun Pharma and Pfizer. Institutional research funding from Neracare, Castle Biosciences, Delcath Systems, Philogen and Provectus, GV Long: Consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Evaxion Biotech A/S, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX B.V. and Specialised Therapeutics Australia Pty Ltd.

Funding Information:
T Hieken: Institutional research funding from Genentech and SkylineDx.

Funding Information:
PA Ascierto: Consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen and iTeos. Research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer and Sanofi.

Funding Information:
N Asher: Advisory boards for Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi. Speaker honoraria from Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, and Sanofi. Institutional research grants from Medison and Novartis .

Funding Information:
A van Akkooi: Advisory Board and Consultancy Honoraria from Amgen, Bristol-Myers Squibb, Novartis, Merck Sharp & Dhome, Merck, Pfizer, Pierre Fabre, Sanofi, Sirius Medical and 4SC. Research grants from Amgen , Merck and Pfizer . All unrelated to current work and paid to institute.

Funding Information:
R Olofsson Bagge: Advisory boards for Amgen, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi Genzyme. Speaker honorarium from Roche and Pfizer. Institutional research grant from Astra Zeneca and SkylineDx .

Funding Information:
The Swedish Cancer Society (Dnr 19 0040 Pj). Knut and Alice Wallenberg Foundation, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SwedenR Olofsson Bagge: Advisory boards for Amgen, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi Genzyme. Speaker honorarium from Roche and Pfizer. Institutional research grant from Astra Zeneca and SkylineDx.M Block: Advisory Boards TILT Biotherapeutics, Viewpoint Molecular Targeting and Sorrento Therapeutics. Grant/Research support from: Genentech, Marker Therapeutics, Immune Design, Pharmacyclics, Merck, Bristol-Myers Squibb, Transgene, Viewpoint Molecular Targeting and Sorrento Therapeutics.N Asher: Advisory boards for Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi. Speaker honoraria from Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, and Sanofi. Institutional research grants from Medison and Novartis.A van Akkooi: Advisory Board and Consultancy Honoraria from Amgen, Bristol-Myers Squibb, Novartis, Merck Sharp & Dhome, Merck, Pfizer, Pierre Fabre, Sanofi, Sirius Medical and 4SC. Research grants from Amgen, Merck and Pfizer. All unrelated to current work and paid to institute.

Publisher Copyright:
© 2022 The Authors

Keywords

Immune checkpoint inhibitor
In-transit metastasis
Ipilimumab
Melanoma
Nivolumab
PD-1
Pembrolizumab

PubMed: MeSH publication types

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

UN SDGs

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

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10.1016/j.ejca.2022.03.041

http://www.ejcancer.com/article/S0959804922001897/pdfLicense: CC BY

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@article{33316410d3804772a10cd7f20f32f0e6,

title = "The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.",

abstract = "PurposeGuidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics.MethodsA multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions.ResultsA total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively.ConclusionSystemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.",

keywords = "Immune checkpoint inhibitor, In-transit metastasis, Ipilimumab, Melanoma, Nivolumab, PD-1, Pembrolizumab",

author = "Jane Hui",

note = "Funding Information: J Weber: Consult for Merck, Genentech, Astra Zeneca, GlaxoSmithKline, Novartis, Nektar, Celldex, Incyte, Biond, ImCheck, Sellas, Evaxion and EMD Serono. Advisory board member Bristol-Myers Squibb. Equity in Biond, Evaxion, Instil Bio and Neximmune. Scientific advisory boards for CytoMx, Incyte, ImCheck, Biond, Sellas, Instil Bio OncoC4 and Neximmune. Institutional research support from Bristol-Myers Squibb, Merck, GlaxoSmithKline, Moderna, Pfizer, Novartis and Astra Zeneca. Named on patents from Moffitt Cancer Center and Biodesix. Funding Information: D Ollila: Advisory boards and/or Consulting for Philogen, Merck, Novartis and Castle Biosciences. Medical Advisory Bopard - Delcath Systems. Speaker honorarium from Sun Pharma and Pfizer. Institutional research funding from Neracare, Castle Biosciences, Delcath Systems, Philogen and Provectus, GV Long: Consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Evaxion Biotech A/S, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX B.V. and Specialised Therapeutics Australia Pty Ltd. Funding Information: T Hieken: Institutional research funding from Genentech and SkylineDx. Funding Information: PA Ascierto: Consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen and iTeos. Research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer and Sanofi. Funding Information: N Asher: Advisory boards for Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi. Speaker honoraria from Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, and Sanofi. Institutional research grants from Medison and Novartis . Funding Information: A van Akkooi: Advisory Board and Consultancy Honoraria from Amgen, Bristol-Myers Squibb, Novartis, Merck Sharp & Dhome, Merck, Pfizer, Pierre Fabre, Sanofi, Sirius Medical and 4SC. Research grants from Amgen , Merck and Pfizer . All unrelated to current work and paid to institute. Funding Information: R Olofsson Bagge: Advisory boards for Amgen, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi Genzyme. Speaker honorarium from Roche and Pfizer. Institutional research grant from Astra Zeneca and SkylineDx . Funding Information: The Swedish Cancer Society (Dnr 19 0040 Pj). Knut and Alice Wallenberg Foundation, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SwedenR Olofsson Bagge: Advisory boards for Amgen, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi Genzyme. Speaker honorarium from Roche and Pfizer. Institutional research grant from Astra Zeneca and SkylineDx.M Block: Advisory Boards TILT Biotherapeutics, Viewpoint Molecular Targeting and Sorrento Therapeutics. Grant/Research support from: Genentech, Marker Therapeutics, Immune Design, Pharmacyclics, Merck, Bristol-Myers Squibb, Transgene, Viewpoint Molecular Targeting and Sorrento Therapeutics.N Asher: Advisory boards for Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi. Speaker honoraria from Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, and Sanofi. Institutional research grants from Medison and Novartis.A van Akkooi: Advisory Board and Consultancy Honoraria from Amgen, Bristol-Myers Squibb, Novartis, Merck Sharp & Dhome, Merck, Pfizer, Pierre Fabre, Sanofi, Sirius Medical and 4SC. Research grants from Amgen, Merck and Pfizer. All unrelated to current work and paid to institute. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jul,

doi = "10.1016/j.ejca.2022.03.041",

language = "English",

volume = "169",

pages = "210--222",

journal = "European journal of cancer (Oxford, England : 1990)",

}

TY - JOUR

T1 - The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

AU - Hui, Jane

N1 - Funding Information: J Weber: Consult for Merck, Genentech, Astra Zeneca, GlaxoSmithKline, Novartis, Nektar, Celldex, Incyte, Biond, ImCheck, Sellas, Evaxion and EMD Serono. Advisory board member Bristol-Myers Squibb. Equity in Biond, Evaxion, Instil Bio and Neximmune. Scientific advisory boards for CytoMx, Incyte, ImCheck, Biond, Sellas, Instil Bio OncoC4 and Neximmune. Institutional research support from Bristol-Myers Squibb, Merck, GlaxoSmithKline, Moderna, Pfizer, Novartis and Astra Zeneca. Named on patents from Moffitt Cancer Center and Biodesix. Funding Information: D Ollila: Advisory boards and/or Consulting for Philogen, Merck, Novartis and Castle Biosciences. Medical Advisory Bopard - Delcath Systems. Speaker honorarium from Sun Pharma and Pfizer. Institutional research funding from Neracare, Castle Biosciences, Delcath Systems, Philogen and Provectus, GV Long: Consultant advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Evaxion Biotech A/S, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX B.V. and Specialised Therapeutics Australia Pty Ltd. Funding Information: T Hieken: Institutional research funding from Genentech and SkylineDx. Funding Information: PA Ascierto: Consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen and iTeos. Research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer and Sanofi. Funding Information: N Asher: Advisory boards for Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi. Speaker honoraria from Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, and Sanofi. Institutional research grants from Medison and Novartis . Funding Information: A van Akkooi: Advisory Board and Consultancy Honoraria from Amgen, Bristol-Myers Squibb, Novartis, Merck Sharp & Dhome, Merck, Pfizer, Pierre Fabre, Sanofi, Sirius Medical and 4SC. Research grants from Amgen , Merck and Pfizer . All unrelated to current work and paid to institute. Funding Information: R Olofsson Bagge: Advisory boards for Amgen, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi Genzyme. Speaker honorarium from Roche and Pfizer. Institutional research grant from Astra Zeneca and SkylineDx . Funding Information: The Swedish Cancer Society (Dnr 19 0040 Pj). Knut and Alice Wallenberg Foundation, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, SwedenR Olofsson Bagge: Advisory boards for Amgen, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi Genzyme. Speaker honorarium from Roche and Pfizer. Institutional research grant from Astra Zeneca and SkylineDx.M Block: Advisory Boards TILT Biotherapeutics, Viewpoint Molecular Targeting and Sorrento Therapeutics. Grant/Research support from: Genentech, Marker Therapeutics, Immune Design, Pharmacyclics, Merck, Bristol-Myers Squibb, Transgene, Viewpoint Molecular Targeting and Sorrento Therapeutics.N Asher: Advisory boards for Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, Roche, and Sanofi. Speaker honoraria from Medison, Bristol-Myers Squibb, Merck Sharp & Dhome, Novartis, and Sanofi. Institutional research grants from Medison and Novartis.A van Akkooi: Advisory Board and Consultancy Honoraria from Amgen, Bristol-Myers Squibb, Novartis, Merck Sharp & Dhome, Merck, Pfizer, Pierre Fabre, Sanofi, Sirius Medical and 4SC. Research grants from Amgen, Merck and Pfizer. All unrelated to current work and paid to institute. Publisher Copyright: © 2022 The Authors

PY - 2022/7

Y1 - 2022/7

N2 - PurposeGuidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics.MethodsA multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions.ResultsA total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively.ConclusionSystemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

AB - PurposeGuidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics.MethodsA multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions.ResultsA total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively.ConclusionSystemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

KW - Immune checkpoint inhibitor

KW - In-transit metastasis

KW - Ipilimumab

KW - Melanoma

KW - Nivolumab

KW - PD-1

KW - Pembrolizumab

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M3 - Article

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JO - European journal of cancer (Oxford, England : 1990)

JF - European journal of cancer (Oxford, England : 1990)

ER -

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study.

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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