Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy

E J van Dijk; H H Nienhuis; A J M van den Eertwegh; M J Boers-Sonderen; M Bloem; A M Kamphuis; M M Ros; C Bos; M J B Aarts; F W P J van den Berkmortel; C U Blank; W A M Blokx; J W B de Groot; G A P Hospers; D Piersma; R S van Rijn; A M Stevense-den Boer; G Vreugdenhil; M W J M Wouters; E Kapiteijn; J B Haanen; A A M van der Veldt; K P M Suijkerbuijk

doi:10.1038/s41416-025-03027-z

Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy

E J van Dijk^*
, H H Nienhuis
, A J M van den Eertwegh
, M J Boers-Sonderen
, M Bloem
, A M Kamphuis
, M M Ros
, C Bos
, M J B Aarts
, F W P J van den Berkmortel
, C U Blank
, W A M Blokx
, J W B de Groot
, G A P Hospers
, D Piersma
, R S van Rijn
, A M Stevense-den Boer
, G Vreugdenhil
, M W J M Wouters
, E Kapiteijn

J B Haanen, A A M van der Veldt, K P M Suijkerbuijk

^*Corresponding author for this work

Personalized Cancer Treatment (PCT)

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

Abstract

BACKGROUND: Ipilimumab+nivolumab (IPINIVO) can induce durable responses in advanced melanoma, but many patients experience progression at some point. It is currently unknown to what extent these patients benefit from IPINIVO rechallenge. This study describes efficacy and safety of IPINIVO rechallenge.

METHODS: Data from advanced melanoma patients rechallenged with IPINIVO after previous ipilimumab-containing treatment were retrieved from the nationwide Dutch Melanoma Treatment Registry. Patient characteristics, responses, survival, and safety were analyzed.

RESULTS: Among 3.759 patients receiving ipilimumab-containing treatment, 73 received rechallenge IPINIVO. 41 received IPINIVO, 32 ipilimumab monotherapy (IPI) as initial therapy. Objective response to rechallenge IPINIVO was seen in 36.1% (initial IPINIVO) and 40.0% (initial IPI) of patients. Median progression-free survival after rechallenge was 2.8 months (initial IPINIVO) and 5.6 months (initial IPI), but reached 18.4 months for responders to rechallenge therapy. Grade ≥3 immune-related adverse events occurred in 40.5% (initial IPINIVO) and 38.7% (initial IPI) of patients. Objective responses to initial and rechallenge treatment were discordant in 48.6% (initial IPINIVO) and 53.3% (initial IPI) of patients. Fifteen patients (20.5%) responded to rechallenge therapy but not to initial treatment.

CONCLUSIONS: Rechallenge IPINIVO after previous ipilimumab-based therapy had a considerable response rate, acceptable safety profile, and potential for a durable response.

Original language	English
Pages (from-to)	66–75
Number of pages	10
Journal	British Journal of Cancer
Volume	133
Early online date	29-Apr-2025
DOIs	https://doi.org/10.1038/s41416-025-03027-z
Publication status	Published - 27-Jul-2025

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Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapyFinal publisher's version, 564 KBLicence: Taverne

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van Dijk, E. J., Nienhuis, H. H., van den Eertwegh, A. J. M., Boers-Sonderen, M. J., Bloem, M., Kamphuis, A. M., Ros, M. M., Bos, C., Aarts, M. J. B., van den Berkmortel, F. W. P. J., Blank, C. U., Blokx, W. A. M., de Groot, J. W. B., Hospers, G. A. P., Piersma, D., van Rijn, R. S., Stevense-den Boer, A. M., Vreugdenhil, G., Wouters, M. W. J. M., ... Suijkerbuijk, K. P. M. (2025). Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy. British Journal of Cancer, 133, 66–75. https://doi.org/10.1038/s41416-025-03027-z

@article{ec48ba076a1844c696946811bd885892,

title = "Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy",

abstract = "BACKGROUND: Ipilimumab+nivolumab (IPINIVO) can induce durable responses in advanced melanoma, but many patients experience progression at some point. It is currently unknown to what extent these patients benefit from IPINIVO rechallenge. This study describes efficacy and safety of IPINIVO rechallenge.METHODS: Data from advanced melanoma patients rechallenged with IPINIVO after previous ipilimumab-containing treatment were retrieved from the nationwide Dutch Melanoma Treatment Registry. Patient characteristics, responses, survival, and safety were analyzed.RESULTS: Among 3.759 patients receiving ipilimumab-containing treatment, 73 received rechallenge IPINIVO. 41 received IPINIVO, 32 ipilimumab monotherapy (IPI) as initial therapy. Objective response to rechallenge IPINIVO was seen in 36.1\% (initial IPINIVO) and 40.0\% (initial IPI) of patients. Median progression-free survival after rechallenge was 2.8 months (initial IPINIVO) and 5.6 months (initial IPI), but reached 18.4 months for responders to rechallenge therapy. Grade ≥3 immune-related adverse events occurred in 40.5\% (initial IPINIVO) and 38.7\% (initial IPI) of patients. Objective responses to initial and rechallenge treatment were discordant in 48.6\% (initial IPINIVO) and 53.3\% (initial IPI) of patients. Fifteen patients (20.5\%) responded to rechallenge therapy but not to initial treatment.CONCLUSIONS: Rechallenge IPINIVO after previous ipilimumab-based therapy had a considerable response rate, acceptable safety profile, and potential for a durable response.",

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

note = "{\textcopyright} 2025. The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2025",

month = jul,

day = "27",

doi = "10.1038/s41416-025-03027-z",

language = "English",

volume = "133",

pages = "66–75",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

}

van Dijk, EJ, Nienhuis, HH, van den Eertwegh, AJM, Boers-Sonderen, MJ, Bloem, M, Kamphuis, AM, Ros, MM, Bos, C, Aarts, MJB, van den Berkmortel, FWPJ, Blank, CU, Blokx, WAM, de Groot, JWB, Hospers, GAP, Piersma, D, van Rijn, RS, Stevense-den Boer, AM, Vreugdenhil, G, Wouters, MWJM, Kapiteijn, E, Haanen, JB, van der Veldt, AAM & Suijkerbuijk, KPM 2025, 'Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy', British Journal of Cancer, vol. 133, pp. 66–75. https://doi.org/10.1038/s41416-025-03027-z

TY - JOUR

T1 - Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy

AU - van Dijk, E J

AU - Nienhuis, H H

AU - van den Eertwegh, A J M

AU - Boers-Sonderen, M J

AU - Bloem, M

AU - Kamphuis, A M

AU - Ros, M M

AU - Bos, C

AU - Aarts, M J B

AU - van den Berkmortel, F W P J

AU - Blank, C U

AU - Blokx, W A M

AU - de Groot, J W B

AU - Hospers, G A P

AU - Piersma, D

AU - van Rijn, R S

AU - Stevense-den Boer, A M

AU - Vreugdenhil, G

AU - Wouters, M W J M

AU - Kapiteijn, E

AU - Haanen, J B

AU - van der Veldt, A A M

AU - Suijkerbuijk, K P M

PY - 2025/7/27

Y1 - 2025/7/27

N2 - BACKGROUND: Ipilimumab+nivolumab (IPINIVO) can induce durable responses in advanced melanoma, but many patients experience progression at some point. It is currently unknown to what extent these patients benefit from IPINIVO rechallenge. This study describes efficacy and safety of IPINIVO rechallenge.METHODS: Data from advanced melanoma patients rechallenged with IPINIVO after previous ipilimumab-containing treatment were retrieved from the nationwide Dutch Melanoma Treatment Registry. Patient characteristics, responses, survival, and safety were analyzed.RESULTS: Among 3.759 patients receiving ipilimumab-containing treatment, 73 received rechallenge IPINIVO. 41 received IPINIVO, 32 ipilimumab monotherapy (IPI) as initial therapy. Objective response to rechallenge IPINIVO was seen in 36.1% (initial IPINIVO) and 40.0% (initial IPI) of patients. Median progression-free survival after rechallenge was 2.8 months (initial IPINIVO) and 5.6 months (initial IPI), but reached 18.4 months for responders to rechallenge therapy. Grade ≥3 immune-related adverse events occurred in 40.5% (initial IPINIVO) and 38.7% (initial IPI) of patients. Objective responses to initial and rechallenge treatment were discordant in 48.6% (initial IPINIVO) and 53.3% (initial IPI) of patients. Fifteen patients (20.5%) responded to rechallenge therapy but not to initial treatment.CONCLUSIONS: Rechallenge IPINIVO after previous ipilimumab-based therapy had a considerable response rate, acceptable safety profile, and potential for a durable response.

AB - BACKGROUND: Ipilimumab+nivolumab (IPINIVO) can induce durable responses in advanced melanoma, but many patients experience progression at some point. It is currently unknown to what extent these patients benefit from IPINIVO rechallenge. This study describes efficacy and safety of IPINIVO rechallenge.METHODS: Data from advanced melanoma patients rechallenged with IPINIVO after previous ipilimumab-containing treatment were retrieved from the nationwide Dutch Melanoma Treatment Registry. Patient characteristics, responses, survival, and safety were analyzed.RESULTS: Among 3.759 patients receiving ipilimumab-containing treatment, 73 received rechallenge IPINIVO. 41 received IPINIVO, 32 ipilimumab monotherapy (IPI) as initial therapy. Objective response to rechallenge IPINIVO was seen in 36.1% (initial IPINIVO) and 40.0% (initial IPI) of patients. Median progression-free survival after rechallenge was 2.8 months (initial IPINIVO) and 5.6 months (initial IPI), but reached 18.4 months for responders to rechallenge therapy. Grade ≥3 immune-related adverse events occurred in 40.5% (initial IPINIVO) and 38.7% (initial IPI) of patients. Objective responses to initial and rechallenge treatment were discordant in 48.6% (initial IPINIVO) and 53.3% (initial IPI) of patients. Fifteen patients (20.5%) responded to rechallenge therapy but not to initial treatment.CONCLUSIONS: Rechallenge IPINIVO after previous ipilimumab-based therapy had a considerable response rate, acceptable safety profile, and potential for a durable response.

U2 - 10.1038/s41416-025-03027-z

DO - 10.1038/s41416-025-03027-z

M3 - Article

C2 - 40295727

SN - 0007-0920

VL - 133

SP - 66

EP - 75

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

Rechallenge of ipilimumab and nivolumab in advanced melanoma patients after previous ipilimumab-based therapy

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