Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors†

Nienke A. de Glas; Esther Bastiaannet; Frederiek van den Bos; Simon P. Mooijaart; Astrid A.M. van der Veldt; Karlijn P.M. Suijkerbuijk; Maureen J.B. Aarts; Franchette W.P.J. van den Berkmortel; Christian U. Blank; Marye J. Boers-Sonderen; Alfonsus J.M. van den Eertwegh; Jan Willem B. de Groot; John B.A.G. Haanen; Geke A.P. Hospers; Hilde Jalving; Djura Piersma; Rozemarijn S. van Rijn; Albert J. Ten Tije; Gerard Vreugdenhil; Michel W.J.M. Wouters; Johanneke E.A. Portielje; Ellen W. Kapiteijn

doi:10.3390/cancers13112826

Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors^†

Nienke A. de Glas^*
, Esther Bastiaannet
, Frederiek van den Bos
, Simon P. Mooijaart
, Astrid A.M. van der Veldt
, Karlijn P.M. Suijkerbuijk
, Maureen J.B. Aarts
, Franchette W.P.J. van den Berkmortel
, Christian U. Blank
, Marye J. Boers-Sonderen
, Alfonsus J.M. van den Eertwegh
, Jan Willem B. de Groot
, John B.A.G. Haanen
, Geke A.P. Hospers
, Hilde Jalving
, Djura Piersma
, Rozemarijn S. van Rijn
, Albert J. Ten Tije
, Gerard Vreugdenhil
, Michel W.J.M. Wouters

Johanneke E.A. Portielje, Ellen W. Kapiteijn

^*Corresponding author for this work

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

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Abstract

Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of “real-world” older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65–75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.

Original language	English
Article number	2826
Journal	Cancers
Volume	13
Issue number	11
DOIs	https://doi.org/10.3390/cancers13112826
Publication status	Published - 1 Jun 2021

Keywords

Geriatric oncology
Immunotherapy
Melanoma
Older adults
Response
Toxicity

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de Glas, N. A., Bastiaannet, E., van den Bos, F., Mooijaart, S. P., van der Veldt, A. A. M., Suijkerbuijk, K. P. M., Aarts, M. J. B., van den Berkmortel, F. W. P. J., Blank, C. U., Boers-Sonderen, M. J., van den Eertwegh, A. J. M., de Groot, J. W. B., Haanen, J. B. A. G., Hospers, G. A. P., Jalving, H., Piersma, D., van Rijn, R. S., Ten Tije, A. J., Vreugdenhil, G., ... Kapiteijn, E. W. (2021). Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors^†. Cancers, 13(11), Article 2826. https://doi.org/10.3390/cancers13112826

@article{88f5c66bf1e8480a950b3304142d7abb,

title = "Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors†",

abstract = "Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of “real-world” older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3\% and 43.6\% in patients aged 65–75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.",

keywords = "Geriatric oncology, Immunotherapy, Melanoma, Older adults, Response, Toxicity",

author = "\{de Glas\}, \{Nienke A.\} and Esther Bastiaannet and \{van den Bos\}, Frederiek and Mooijaart, \{Simon P.\} and \{van der Veldt\}, \{Astrid A.M.\} and Suijkerbuijk, \{Karlijn P.M.\} and Aarts, \{Maureen J.B.\} and \{van den Berkmortel\}, \{Franchette W.P.J.\} and Blank, \{Christian U.\} and Boers-Sonderen, \{Marye J.\} and \{van den Eertwegh\}, \{Alfonsus J.M.\} and \{de Groot\}, \{Jan Willem B.\} and Haanen, \{John B.A.G.\} and Hospers, \{Geke A.P.\} and Hilde Jalving and Djura Piersma and \{van Rijn\}, \{Rozemarijn S.\} and \{Ten Tije\}, \{Albert J.\} and Gerard Vreugdenhil and Wouters, \{Michel W.J.M.\} and Portielje, \{Johanneke E.A.\} and Kapiteijn, \{Ellen W.\}",

note = "Funding Information: Funding: This study was supported by a personal Veni Grant of the first author, provided by the Dutch Research Council (09150161810003). Funding Information: Conflicts of Interest: N.A. de Glas has received research grants not related to this paper from Pfizer and Novartis. C.U. Blank reports receiving 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 interest in Uniti Cars, Neon Therapeutics, and Forty Seven. M.J. Boers-Sonderen has served as an advisory board member for Bristol-Myers Squibb, Novartis, Merck, and Pierre Fabre. A.J.M. van den Eertwegh has served as a speaker for Bristol-Myers Squibb and Novartis and an advisory board member for Bristol-Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck, and Pierre Fabre and has received research grants not related to this paper from Sanofi, Roche, Bristol-Myers Squibb, TEVA, and Idera. J.W. de Groot is a paid consultant for Bristol-Myers Squibb and MSD. G.A.P. Hospers is an unpaid consultant/advisory board member for Bristol-Myers Squibb, MSD, Roche, and Novartis. M. Jalving has served as an advisory board member for Bristol-Myers Squibb, Novartis, Merck, and Pierre Fabre. Fees to the institution. D. Piersma has served as an advisory board member for Amgen, BMS, and Pierre Fabre. A.A.M. van der Veldt is a paid consultant for Bristol-Myers Squibb, MSD, Novartis, Roche, Pfizer, Eisai, Ipsen, Pierre Fabre, Sanofi, and Bayer. J.B.A.G. Haanen is a paid consultant for BioNTech, BMS, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, Pfizer, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm and reports receiving commercial research grants from Amgen, BioNTech US, Bristol-Myers Squibb, MSD, Novartis, and Neogene Therapeutics. K.P.M. Suijkerbuijk has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, and AbbVie and received honoraria/research support not related to this manuscript from Novartis, Roche, and MSD. All paid to the institution. E. Kapiteijn has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Novartis, Merck, Pierre Fabre and has received research grants not related to this paper from Bristol-Myers Squibb. No potential conflict of interest were disclosed by the other authors. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jun,

day = "1",

doi = "10.3390/cancers13112826",

language = "English",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "11",

}

de Glas, NA, Bastiaannet, E, van den Bos, F, Mooijaart, SP, van der Veldt, AAM, Suijkerbuijk, KPM, Aarts, MJB, van den Berkmortel, FWPJ, Blank, CU, Boers-Sonderen, MJ, van den Eertwegh, AJM, de Groot, JWB, Haanen, JBAG, Hospers, GAP, Jalving, H, Piersma, D, van Rijn, RS, Ten Tije, AJ, Vreugdenhil, G, Wouters, MWJM, Portielje, JEA & Kapiteijn, EW 2021, 'Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors^†', Cancers, vol. 13, no. 11, 2826. https://doi.org/10.3390/cancers13112826

TY - JOUR

T1 - Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors†

AU - de Glas, Nienke A.

AU - Bastiaannet, Esther

AU - van den Bos, Frederiek

AU - Mooijaart, Simon P.

AU - van der Veldt, Astrid A.M.

AU - Suijkerbuijk, Karlijn P.M.

AU - Aarts, Maureen J.B.

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

AU - Blank, Christian U.

AU - Boers-Sonderen, Marye J.

AU - van den Eertwegh, Alfonsus J.M.

AU - de Groot, Jan Willem B.

AU - Haanen, John B.A.G.

AU - Hospers, Geke A.P.

AU - Jalving, Hilde

AU - Piersma, Djura

AU - van Rijn, Rozemarijn S.

AU - Ten Tije, Albert J.

AU - Vreugdenhil, Gerard

AU - Wouters, Michel W.J.M.

AU - Portielje, Johanneke E.A.

AU - Kapiteijn, Ellen W.

N1 - Funding Information: Funding: This study was supported by a personal Veni Grant of the first author, provided by the Dutch Research Council (09150161810003). Funding Information: Conflicts of Interest: N.A. de Glas has received research grants not related to this paper from Pfizer and Novartis. C.U. Blank reports receiving 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 interest in Uniti Cars, Neon Therapeutics, and Forty Seven. M.J. Boers-Sonderen has served as an advisory board member for Bristol-Myers Squibb, Novartis, Merck, and Pierre Fabre. A.J.M. van den Eertwegh has served as a speaker for Bristol-Myers Squibb and Novartis and an advisory board member for Bristol-Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck, and Pierre Fabre and has received research grants not related to this paper from Sanofi, Roche, Bristol-Myers Squibb, TEVA, and Idera. J.W. de Groot is a paid consultant for Bristol-Myers Squibb and MSD. G.A.P. Hospers is an unpaid consultant/advisory board member for Bristol-Myers Squibb, MSD, Roche, and Novartis. M. Jalving has served as an advisory board member for Bristol-Myers Squibb, Novartis, Merck, and Pierre Fabre. Fees to the institution. D. Piersma has served as an advisory board member for Amgen, BMS, and Pierre Fabre. A.A.M. van der Veldt is a paid consultant for Bristol-Myers Squibb, MSD, Novartis, Roche, Pfizer, Eisai, Ipsen, Pierre Fabre, Sanofi, and Bayer. J.B.A.G. Haanen is a paid consultant for BioNTech, BMS, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, Pfizer, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm and reports receiving commercial research grants from Amgen, BioNTech US, Bristol-Myers Squibb, MSD, Novartis, and Neogene Therapeutics. K.P.M. Suijkerbuijk has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, and AbbVie and received honoraria/research support not related to this manuscript from Novartis, Roche, and MSD. All paid to the institution. E. Kapiteijn has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Novartis, Merck, Pierre Fabre and has received research grants not related to this paper from Bristol-Myers Squibb. No potential conflict of interest were disclosed by the other authors. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of “real-world” older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65–75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.

AB - Background: Previous trials suggest no differences in immunotherapy treatment between older and younger patients, but mainly young patients with a good performance status were included. The aim of this study was to describe the treatment patterns and outcomes of “real-world” older patients with metastatic melanoma and to identify predictors of outcome. Methods: We included patients aged ≥65 years with metastatic melanoma from the Dutch Melanoma Treatment Registry. We described the reasons for hospital admissions and treatment discontinuation. Additionally, we assessed predictors of toxicity and response using logistic regression models and survival using Cox regression models. Results: We included 2216 patients. Grade ≥3 toxicity was not associated with age, comorbidities or WHO status. Patients aged ≥75 discontinued treatment due to toxicity more often, resulting in fewer treatment cycles. Response rates were similar to previous trials (40.3% and 43.6% in patients aged 65–75 and ≥75, respectively, for anti-PD1 treatment) and did not decrease with age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity. Conclusion: Response rates and toxicity outcomes of checkpoint inhibitors did not change with increasing age or comorbidity. However, the impact of grade I-II toxicity on quality of life deserves further study as older patients discontinue treatment more frequently.

KW - Geriatric oncology

KW - Immunotherapy

KW - Melanoma

KW - Older adults

KW - Response

KW - Toxicity

UR - https://www.scopus.com/pages/publications/85107333952

U2 - 10.3390/cancers13112826

DO - 10.3390/cancers13112826

M3 - Article

AN - SCOPUS:85107333952

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 11

M1 - 2826

ER -

Toxicity, response and survival in older patients with metastatic melanoma treated with checkpoint inhibitors^†

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Keywords

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