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. 2025 Jul;133(1):66-75.
doi: 10.1038/s41416-025-03027-z. Epub 2025 Apr 29.

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

E J van Dijk  1 , H H Nienhuis  2   3 , A J M van den Eertwegh  4 , M J Boers-Sonderen  5 , M Bloem  6 , A M Kamphuis  2 , M M Ros  2 , C Bos  7 , M J B Aarts  8 , F W P J van den Berkmortel  9 , C U Blank  10 , W A M Blokx  11 , J W B de Groot  12 , G A P Hospers  13 , D Piersma  14 , R S van Rijn  15 , A M Stevense-den Boer  16 , G Vreugdenhil  17 , M W J M Wouters  6   18   19 , E Kapiteijn  20 , J B Haanen  10 , A A M van der Veldt  21 , K P M Suijkerbuijk  2
Affiliations

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

E J van Dijk et al. Br J Cancer. 2025 Jul.

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.

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Conflict of interest statement

Competing interests: HHN has advisory/consultancy relations with Bayer, Roche, Johnson&Johnson, and Illumina. AJME has advisory/consultancy relations with Amgen, Bristol Myers Squibb, Ipsen Biopharmaceuticals, Janssen-Cilag BV, Merck, Merck Sharp & Dohme, Novartis, Pfizer Canada and Pierre Fabre Pharmaceuticals. He received a research grant from Bristol-Myers Squibb, paid to institution. CB received research grants from Philips, Bracco, Sensius, all paid to institution. CUB has advisory/consultancy relations with Bristol Myers Squibb, Roche, Merck and Third Rock Ventures. He received research grants from 4SC, Bristol Myers Squibb, Roche, Merck, NanoString Technologies, all paid to institution. He received an individual research grant from Third Rock Ventures. He is co-founder of Signature Oncology and Imagene BV, and has a pending patent (Patent number WO 2021/177822 A1). GAPH received research grants from Bristol-Myers Squibb and Seerave, all paid to institution. DP has advisory/consultancy relations with Novartis and Pierre Fabre Pharmaceuticals. She received a travel grant from Pierre Fabre Pharmaceuticals. EK has advisory/consultancy relations with Delcath, Immunocore and Lilly, and received research grants not related to this paper from Bristol Myers Squibb, Delcath, Novartis, and Pierre-Fabre. Not related to current work and paid to institute. JBH has advisory/consultancy relations with AZ, BioNTech, CureVac, Eisai, Ipsen, Instil Bio, Iovance Bio, MSD, Novartis, Neogene Therapeutics, Roche, Sanofi, Sastra Cell Therapy, Third Rock Ventures, and T-Knife. He received research grants from Amgen, BioNTech, Bristol Myers Squibb, Novartis, Sastra Cell Therapy. He is editor-in-Chief of ESMO Immmuno-Oncology & Technology (IOTECH). AAMV has advisory/consultancy relations with Bristol-Myers Squibb, MSD, Sanofi, Merck, Pierre Fabre, Novartis, Pfizer, Roche, Eisai and Ipsen. KPMS has advisory/consultancy relations with AbbVie, and Sairopa. She received research grants from Bristol-Myers Squibb, Genmab, Philips, Pierre Fabre, and Tigatx, all paid to institution. She does data and safety monitoring for Sairopa. No other competing interests were reported. Ethics approval and consent to participate: This study was performed in accordance with the Declaration of Helsinki. In compliance with Dutch regulations, research with DMTR data was approved by the medical ethical committee (METC Leiden University Medical Center, 2013) not to be subject to the Medical Research Involving Human Subjects Act, thereby waiving the requirement for informed consent.

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