Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry

A Özkan; E Kapiteijn; F van den Bos; M J B Aarts; F W P J van den Berkmortel; C U Blank; M Bloem; W A M Blokx; M J Boers-Sonderen; J J Bonenkamp; A J M van den Eertwegh; J W B de Groot; J B Haanen; C E Holtslag; G A P Hospers; D Piersma; R S van Rijn; A M Stevense-den Boer; K P M Suijkerbuijk; A A M van der Veldt; G Vreugdenhil; M W J M Wouters; J E A Portielje; N A de Glas

doi:10.1016/j.ejca.2024.115056

Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry

A Özkan
, E Kapiteijn
, F van den Bos
, M J B Aarts
, F W P J van den Berkmortel
, C U Blank
, M Bloem
, W A M Blokx
, M J Boers-Sonderen
, J J Bonenkamp
, A J M van den Eertwegh
, J W B de Groot
, J B Haanen
, C E Holtslag
, G A P Hospers
, D Piersma
, R S van Rijn
, A M Stevense-den Boer
, K P M Suijkerbuijk
, A A M van der Veldt

G Vreugdenhil, M W J M Wouters, J E A Portielje, N A de Glas

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

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Abstract

BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.

METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.

RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44).

CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

Original language	English
Article number	115056
Journal	European Journal of Cancer
Volume	212
Early online date	30 Sept 2024
DOIs	https://doi.org/10.1016/j.ejca.2024.115056
Publication status	Published - Nov 2024

Keywords

Immune checkpoint inhibitors
Immune-related adverse events
Melanoma
Oncology
Recurrence-free survival

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10.1016/j.ejca.2024.115056Licence: CC BY

PIIS0959804924010220Final published version, 698 KBLicence: CC BY

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Özkan, A., Kapiteijn, E., van den Bos, F., Aarts, M. J. B., van den Berkmortel, F. W. P. J., Blank, C. U., Bloem, M., Blokx, W. A. M., Boers-Sonderen, M. J., Bonenkamp, J. J., van den Eertwegh, A. J. M., de Groot, J. W. B., Haanen, J. B., Holtslag, C. E., Hospers, G. A. P., Piersma, D., van Rijn, R. S., Stevense-den Boer, A. M., Suijkerbuijk, K. P. M., ... de Glas, N. A. (2024). Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry. European Journal of Cancer, 212, Article 115056. https://doi.org/10.1016/j.ejca.2024.115056

@article{dfddb40f528049dd8ac559e38782a514,

title = "Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry",

abstract = "BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 \% in the 65-74 age group and 13.9 \% in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 \% C.I. 0.99-3.40). The 1-year RFS rate of 80.0 \% of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 \% C.I. 1.15-2.44).CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.",

keywords = "Immune checkpoint inhibitors, Immune-related adverse events, Melanoma, Oncology, Recurrence-free survival",

author = "A {\"O}zkan and E Kapiteijn and \{van den Bos\}, F and Aarts, \{M J B\} and \{van den Berkmortel\}, \{F W P J\} and Blank, \{C U\} and M Bloem and Blokx, \{W A M\} and Boers-Sonderen, \{M J\} and Bonenkamp, \{J J\} and \{van den Eertwegh\}, \{A J M\} and \{de Groot\}, \{J W B\} and Haanen, \{J B\} and Holtslag, \{C E\} and Hospers, \{G A P\} and D Piersma and \{van Rijn\}, \{R S\} and \{Stevense-den Boer\}, \{A M\} and Suijkerbuijk, \{K P M\} and \{van der Veldt\}, \{A A M\} and G Vreugdenhil and Wouters, \{M W J M\} and Portielje, \{J E A\} and \{de Glas\}, \{N A\}",

note = "Publisher Copyright: {\textcopyright} 2024",

year = "2024",

month = nov,

doi = "10.1016/j.ejca.2024.115056",

language = "English",

volume = "212",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

Özkan, A, Kapiteijn, E, van den Bos, F, Aarts, MJB, van den Berkmortel, FWPJ, Blank, CU, Bloem, M, Blokx, WAM, Boers-Sonderen, MJ, Bonenkamp, JJ, van den Eertwegh, AJM, de Groot, JWB, Haanen, JB, Holtslag, CE, Hospers, GAP, Piersma, D, van Rijn, RS, Stevense-den Boer, AM, Suijkerbuijk, KPM, van der Veldt, AAM, Vreugdenhil, G, Wouters, MWJM, Portielje, JEA & de Glas, NA 2024, 'Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry', European Journal of Cancer, vol. 212, 115056. https://doi.org/10.1016/j.ejca.2024.115056

TY - JOUR

T1 - Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma

T2 - Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry

AU - Özkan, A

AU - Kapiteijn, E

AU - van den Bos, F

AU - Aarts, M J B

AU - van den Berkmortel, F W P J

AU - Blank, C U

AU - Bloem, M

AU - Blokx, W A M

AU - Boers-Sonderen, M J

AU - Bonenkamp, J J

AU - van den Eertwegh, A J M

AU - de Groot, J W B

AU - Haanen, J B

AU - Holtslag, C E

AU - Hospers, G A P

AU - Piersma, D

AU - van Rijn, R S

AU - Stevense-den Boer, A M

AU - Suijkerbuijk, K P M

AU - van der Veldt, A A M

AU - Vreugdenhil, G

AU - Wouters, M W J M

AU - Portielje, J E A

AU - de Glas, N A

PY - 2024/11

Y1 - 2024/11

N2 - BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44).CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

AB - BACKGROUND: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.METHODS: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.RESULTS: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44).CONCLUSION: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

KW - Immune checkpoint inhibitors

KW - Immune-related adverse events

KW - Melanoma

KW - Oncology

KW - Recurrence-free survival

UR - https://www.scopus.com/pages/publications/85205673835

U2 - 10.1016/j.ejca.2024.115056

DO - 10.1016/j.ejca.2024.115056

M3 - Article

C2 - 39368226

SN - 0959-8049

VL - 212

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 115056

ER -

Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry

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Keywords

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Corrigendum to "Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry" [Eur. J. Cancer 212, 2024, 115056]

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