Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Olivier J van Not; Melissa M de Meza; Alfons J M van den Eertwegh; John B Haanen; Christian U Blank; Maureen J B Aarts; Franchette W P J van den Berkmortel; Jesper van Breeschoten; Jan-Willem B de Groot; Geke A P Hospers; Rawa K Ismail; Ellen Kapiteijn; Djura Piersma; Roos S van Rijn; Marion A M Stevense-den Boer; Astrid A M van der Veldt; Gerard Vreugdenhil; Han J Bonenkamp; Marye J Boers-Sonderen; Willeke A M Blokx; Michel W J M Wouters; Karijn P M Suijkerbuijk

doi:10.1016/j.ejca.2022.02.026

Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Olivier J van Not, Melissa M de Meza, Alfons J M van den Eertwegh, John B Haanen, Christian U Blank, Maureen J B Aarts, Franchette W P J van den Berkmortel, Jesper van Breeschoten, Jan-Willem B de Groot, Geke A P Hospers, Rawa K Ismail, Ellen Kapiteijn, Djura Piersma, Roos S van Rijn, Marion A M Stevense-den Boer, Astrid A M van der Veldt, Gerard Vreugdenhil, Han J Bonenkamp, Marye J Boers-Sonderen, Willeke A M BlokxMichel W J M Wouters, Karijn P M Suijkerbuijk

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Abstract

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

Original language	English
Pages (from-to)	70-80
Number of pages	11
Journal	European journal of cancer (Oxford, England : 1990)
Volume	167
DOIs	https://doi.org/10.1016/j.ejca.2022.02.026
Publication status	Published - May 2022

Bibliographical note

Funding Information:
For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organisation, The Netherlands Organisation for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted.

Funding Information:
CB has received commercial research grants from Novartis, BristolMyers 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 interest in Uniti Cars, Neon Therapeutics, and Forty Seven.

Publisher Copyright:
© 2022 The Author(s)

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van Not, O. J., de Meza, M. M., van den Eertwegh, A. J. M., Haanen, J. B., Blank, C. U., Aarts, M. J. B., van den Berkmortel, F. W. P. J., van Breeschoten, J., de Groot, J-W. B., Hospers, G. A. P., Ismail, R. K., Kapiteijn, E., Piersma, D., van Rijn, R. S., Stevense-den Boer, M. A. M., van der Veldt, A. A. M., Vreugdenhil, G., Bonenkamp, H. J., Boers-Sonderen, M. J., ... Suijkerbuijk, K. P. M. (2022). Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study. European journal of cancer (Oxford, England : 1990), 167, 70-80. https://doi.org/10.1016/j.ejca.2022.02.026

@article{1281252effc94c63a5845f4f694e5c5d,

title = "Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study",

abstract = "Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.",

author = "{van Not}, {Olivier J} and {de Meza}, {Melissa M} and {van den Eertwegh}, {Alfons J M} and Haanen, {John B} and Blank, {Christian U} and Aarts, {Maureen J B} and {van den Berkmortel}, {Franchette W P J} and {van Breeschoten}, Jesper and {de Groot}, {Jan-Willem B} and Hospers, {Geke A P} and Ismail, {Rawa K} and Ellen Kapiteijn and Djura Piersma and {van Rijn}, {Roos S} and {Stevense-den Boer}, {Marion A M} and {van der Veldt}, {Astrid A M} and Gerard Vreugdenhil and Bonenkamp, {Han J} and Boers-Sonderen, {Marye J} and Blokx, {Willeke A M} and Wouters, {Michel W J M} and Suijkerbuijk, {Karijn P M}",

note = "Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organisation, The Netherlands Organisation for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted. Funding Information: CB has received commercial research grants from Novartis, BristolMyers 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 interest in Uniti Cars, Neon Therapeutics, and Forty Seven. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = may,

doi = "10.1016/j.ejca.2022.02.026",

language = "English",

volume = "167",

pages = "70--80",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

}

van Not, OJ, de Meza, MM, van den Eertwegh, AJM, Haanen, JB, Blank, CU, Aarts, MJB, van den Berkmortel, FWPJ, van Breeschoten, J, de Groot, J-WB, Hospers, GAP, Ismail, RK, Kapiteijn, E, Piersma, D, van Rijn, RS, Stevense-den Boer, MAM, van der Veldt, AAM, Vreugdenhil, G, Bonenkamp, HJ, Boers-Sonderen, MJ, Blokx, WAM, Wouters, MWJM & Suijkerbuijk, KPM 2022, 'Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study', European journal of cancer (Oxford, England : 1990), vol. 167, pp. 70-80. https://doi.org/10.1016/j.ejca.2022.02.026

TY - JOUR

T1 - Response to immune checkpoint inhibitors in acral melanoma

T2 - A nationwide cohort study

AU - van Not, Olivier J

AU - de Meza, Melissa M

AU - van den Eertwegh, Alfons J M

AU - Haanen, John B

AU - Blank, Christian U

AU - Aarts, Maureen J B

AU - van den Berkmortel, Franchette W P J

AU - van Breeschoten, Jesper

AU - de Groot, Jan-Willem B

AU - Hospers, Geke A P

AU - Ismail, Rawa K

AU - Kapiteijn, Ellen

AU - Piersma, Djura

AU - van Rijn, Roos S

AU - Stevense-den Boer, Marion A M

AU - van der Veldt, Astrid A M

AU - Vreugdenhil, Gerard

AU - Bonenkamp, Han J

AU - Boers-Sonderen, Marye J

AU - Blokx, Willeke A M

AU - Wouters, Michel W J M

AU - Suijkerbuijk, Karijn P M

N1 - Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organisation, The Netherlands Organisation for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted. Funding Information: CB has received commercial research grants from Novartis, BristolMyers 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 interest in Uniti Cars, Neon Therapeutics, and Forty Seven. Publisher Copyright: © 2022 The Author(s)

PY - 2022/5

Y1 - 2022/5

N2 - Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

AB - Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

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U2 - 10.1016/j.ejca.2022.02.026

DO - 10.1016/j.ejca.2022.02.026

M3 - Article

C2 - 35395553

SN - 0959-8049

VL - 167

SP - 70

EP - 80

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Abstract

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