A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

Olivier J. van Not; Thijs T. Wind; Rawa K. Ismail; Arkajyoti Bhattacharya; Mathilde Jalving; Christian U. Blank; Maureen J. B. Aarts; Franchette W. P. J. van den Berkmortel; Marye J. Boers-Sonderen; Alfonsus J. M. van den Eertwegh; Jan Willem B. de Groot; John B. Haanen; Ellen Kapiteijn; Manja Bloem; Djura Piersma; Rozemarijn S. van Rijn; Marion Stevense-den Boer; Astrid A. M. van der Veldt; Gerard Vreugdenhil; Michel W. J. M. Wouters; Willeke A. M. Blokx; Karijn P. M. Suijkerbuijk; Rudolf S. N. Fehrmann; Geke A. P. Hospers

doi:https://doi.org/10.3390/cancers15112922

A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

Olivier J. van Not, Thijs T. Wind, Rawa K. Ismail, Arkajyoti Bhattacharya, Mathilde Jalving, Christian U. Blank, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Marye J. Boers-Sonderen, Alfonsus J. M. van den Eertwegh, Jan Willem B. de Groot, John B. Haanen, Ellen Kapiteijn, Manja Bloem, Djura Piersma, Rozemarijn S. van Rijn, Marion Stevense-den Boer, Astrid A. M. van der Veldt, Gerard Vreugdenhil, Michel W. J. M. WoutersWilleke A. M. Blokx, Karijn P. M. Suijkerbuijk, Rudolf S. N. Fehrmann, Geke A. P. Hospers

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

Abstract

The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients’ survival based on their baseline and disease characteristics.

Original language	English
Article number	2922
Journal	Cancers
Volume	15
Issue number	11
DOIs	https://doi.org/10.3390/cancers15112922
Publication status	Published - 1 Jun 2023

Keywords

advanced melanoma
brain metastases
immunotherapy
survival tree

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https://doi.org/10.3390/cancers15112922

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van Not, O. J., Wind, T. T., Ismail, R. K., Bhattacharya, A., Jalving, M., Blank, C. U., Aarts, M. J. B., van den Berkmortel, F. W. P. J., Boers-Sonderen, M. J., van den Eertwegh, A. J. M., de Groot, J. W. B., Haanen, J. B., Kapiteijn, E., Bloem, M., Piersma, D., van Rijn, R. S., Stevense-den Boer, M., van der Veldt, A. A. M., Vreugdenhil, G., ... Hospers, G. A. P. (2023). A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors. Cancers, 15(11), Article 2922. https://doi.org/10.3390/cancers15112922

@article{adcdf41f724742e697520a588095f49e,

title = "A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors",

abstract = "The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients{\textquoteright} survival based on their baseline and disease characteristics.",

keywords = "advanced melanoma, brain metastases, immunotherapy, survival tree",

author = "{van Not}, {Olivier J.} and Wind, {Thijs T.} and Ismail, {Rawa K.} and Arkajyoti Bhattacharya and Mathilde Jalving and Blank, {Christian U.} and Aarts, {Maureen J. B.} and {van den Berkmortel}, {Franchette W. P. J.} and Boers-Sonderen, {Marye J.} and {van den Eertwegh}, {Alfonsus J. M.} and {de Groot}, {Jan Willem B.} and Haanen, {John B.} and Ellen Kapiteijn and Manja Bloem and Djura Piersma and {van Rijn}, {Rozemarijn S.} and {Stevense-den Boer}, Marion and {van der Veldt}, {Astrid A. M.} and Gerard Vreugdenhil and Wouters, {Michel W. J. M.} and Blokx, {Willeke A. M.} and Suijkerbuijk, {Karijn P. M.} and Fehrmann, {Rudolf S. N.} and Hospers, {Geke A. P.}",

note = "Funding Information: R.I. has no declarations of interest for this research however is employed at MSD since January 2022. A.v.d.E. has advisory relationships with Amgen, Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, and Merck, has received research study grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, Idera, and TEVA, has received travel expenses from MSD Oncology, Roche, Pfizer, and Sanofi, and has received speaker honoraria from BMS and Novartis. J.H. has advisory relationships with Aimm, Achilles Therapeutics, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, BioNTech, GSK, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm and has received research grants not related to this paper from Amgen, Bristol Myers Squibb, MSD, BioNTech, Neogene Therapeutics, and Novartis. All grants were paid to the institutions. M.J. has advisory relationships with AstraZeneca, Bristol Myers Squibb, Pierre Fabre, and GSK. All grants were paid to the institution. C.B. has received commercial research grants from Novartis, Bristol Myers Squibb, and NanoString, is a paid advisory board member for Bristol Myers Squibb, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre, and holds ownership interests in Uniti Cars, Neon Therapeutics, and Forty Seven. M.A. has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer. Research grants have been received from Merck-Pfizer, not related to current work and paid to the institute. J.d.G. has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, and Novartis. G.H. has consultancy/advisory relationships with Amgen, Bristol Myers Squibb, Roche, MSD, Pfizer, Novartis, and Pierre Fabre and has received research grants unrelated to this paper from Bristol Myers Squibb and Seerave and were paid to the institution. E.K. has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, Lilly, and Bayer; these were paid to the institution. Furthermore, she received research grants not related to this paper from Bristol Myers Squibb, Delcath, Novartis, and Pierre Fabre. R.v.R. has advisory board/consultancy honoraria from Pfizer and an expert meeting fee from Roche. A.v.d.V. has consultancy relationships with Bristol Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, and Merck (all paid to the institute). M.B.S. has consultancy/advisory relationships with Pierre Fabre, MSD, and Novartis. K.S. has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre, and AbbVie and received honoraria from Novartis, MSD, and Roche. All remaining authors have declared no conflicts of interest. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = jun,

day = "1",

doi = "https://doi.org/10.3390/cancers15112922",

language = "English",

volume = "15",

journal = "Cancers",

issn = "2072-6694",

publisher = "MDPI Multidisciplinary Digital Publishing Institute",

number = "11",

}

van Not, OJ, Wind, TT, Ismail, RK, Bhattacharya, A, Jalving, M, Blank, CU, Aarts, MJB, van den Berkmortel, FWPJ, Boers-Sonderen, MJ, van den Eertwegh, AJM, de Groot, JWB, Haanen, JB, Kapiteijn, E, Bloem, M, Piersma, D, van Rijn, RS, Stevense-den Boer, M, van der Veldt, AAM, Vreugdenhil, G, Wouters, MWJM, Blokx, WAM, Suijkerbuijk, KPM, Fehrmann, RSN & Hospers, GAP 2023, 'A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors', Cancers, vol. 15, no. 11, 2922. https://doi.org/10.3390/cancers15112922

TY - JOUR

T1 - A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

AU - van Not, Olivier J.

AU - Wind, Thijs T.

AU - Ismail, Rawa K.

AU - Bhattacharya, Arkajyoti

AU - Jalving, Mathilde

AU - Blank, Christian U.

AU - Aarts, Maureen J. B.

AU - van den Berkmortel, Franchette W. P. J.

AU - Boers-Sonderen, Marye J.

AU - van den Eertwegh, Alfonsus J. M.

AU - de Groot, Jan Willem B.

AU - Haanen, John B.

AU - Kapiteijn, Ellen

AU - Bloem, Manja

AU - Piersma, Djura

AU - van Rijn, Rozemarijn S.

AU - Stevense-den Boer, Marion

AU - van der Veldt, Astrid A. M.

AU - Vreugdenhil, Gerard

AU - Wouters, Michel W. J. M.

AU - Blokx, Willeke A. M.

AU - Suijkerbuijk, Karijn P. M.

AU - Fehrmann, Rudolf S. N.

AU - Hospers, Geke A. P.

N1 - Funding Information: R.I. has no declarations of interest for this research however is employed at MSD since January 2022. A.v.d.E. has advisory relationships with Amgen, Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, and Merck, has received research study grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, Idera, and TEVA, has received travel expenses from MSD Oncology, Roche, Pfizer, and Sanofi, and has received speaker honoraria from BMS and Novartis. J.H. has advisory relationships with Aimm, Achilles Therapeutics, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, BioNTech, GSK, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm and has received research grants not related to this paper from Amgen, Bristol Myers Squibb, MSD, BioNTech, Neogene Therapeutics, and Novartis. All grants were paid to the institutions. M.J. has advisory relationships with AstraZeneca, Bristol Myers Squibb, Pierre Fabre, and GSK. All grants were paid to the institution. C.B. has received commercial research grants from Novartis, Bristol Myers Squibb, and NanoString, is a paid advisory board member for Bristol Myers Squibb, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre, and holds ownership interests in Uniti Cars, Neon Therapeutics, and Forty Seven. M.A. has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer. Research grants have been received from Merck-Pfizer, not related to current work and paid to the institute. J.d.G. has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, and Novartis. G.H. has consultancy/advisory relationships with Amgen, Bristol Myers Squibb, Roche, MSD, Pfizer, Novartis, and Pierre Fabre and has received research grants unrelated to this paper from Bristol Myers Squibb and Seerave and were paid to the institution. E.K. has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, Lilly, and Bayer; these were paid to the institution. Furthermore, she received research grants not related to this paper from Bristol Myers Squibb, Delcath, Novartis, and Pierre Fabre. R.v.R. has advisory board/consultancy honoraria from Pfizer and an expert meeting fee from Roche. A.v.d.V. has consultancy relationships with Bristol Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, and Merck (all paid to the institute). M.B.S. has consultancy/advisory relationships with Pierre Fabre, MSD, and Novartis. K.S. has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre, and AbbVie and received honoraria from Novartis, MSD, and Roche. All remaining authors have declared no conflicts of interest. Publisher Copyright: © 2023 by the authors.

PY - 2023/6/1

Y1 - 2023/6/1

N2 - The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients’ survival based on their baseline and disease characteristics.

AB - The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients’ survival based on their baseline and disease characteristics.

KW - advanced melanoma

KW - brain metastases

KW - immunotherapy

KW - survival tree

UR - http://www.scopus.com/inward/record.url?scp=85161439815&partnerID=8YFLogxK

U2 - https://doi.org/10.3390/cancers15112922

DO - https://doi.org/10.3390/cancers15112922

M3 - Article

C2 - 37296885

SN - 2072-6694

VL - 15

JO - Cancers

JF - Cancers

IS - 11

M1 - 2922

ER -

A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

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