Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands

Michiel C T van Zeijl, Jesper van Breeschoten, Liesbeth C de Wreede, Michel W J M Wouters, Doranne L Hilarius, Christian U Blank, Maureen J B Aarts, Franchette W P J van den Berkmortel, Jan Willem B de Groot, Geke A P Hospers, Ellen Kapiteijn, Djura Piersma, Rozemarijn S van Rijn, Marion A Stevense-den Boer, Astrid A M van der Veldt, Gerard Vreugdenhil, Marye J Boers-Sonderen, Karijn P M Suijkerbuijk, John B A G Haanen, Alfons J M van den Eertwegh*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


In phase III trials, ipilimumab plus nivolumab combination therapy is highly efficacious for advanced melanoma, despite many treatment-related grades 3-4 adverse events. Here, we report real-world safety and survival outcomes of ipilimumab plus nivolumab for advanced melanoma. Patients with advanced melanoma who received first-line ipilimumab plus nivolumab between January 1, 2015 and June 30, 2021 were selected from the Dutch Melanoma Treatment Registry. We evaluated response status at 3, 6, 12, 18, and 24 months. OS and PFS were estimated with the Kaplan-Meier method. Separate analyses were performed for patients with or without brain metastases and for patients who met the inclusion criteria of the Checkmate-067 trial. In total, 709 patients received first-line ipilimumab plus nivolumab. Three hundred sixty (50.7%) patients experienced grade 3-4 adverse events, with 211 of the (58.6%) patients requiring hospital admission. The median treatment duration was 42 days (IQR = 31-139). At 24 months, disease control was achieved in 37% of patients. Median PFS since the start of treatment was 6.6 months (95% CI: 5.3-8.7), and median OS was 28.7 months (95% CI: 20.7-42.2). CheckMate-067 trial-like patients had a 4-year OS of 50% (95% CI: 43-59). Among patients with no asymptomatic or symptomatic brain metastases, the 4-year OS probabilities were 48% (95% CI: 41-55), 45% (95% CI: 35-57), and 32% (95% CI: 23-46). Ipilimumab plus nivolumab can achieve long-term survival in advanced melanoma patients in a real-world setting, including patients not represented in the CheckMate-067 trial. However, the proportion of patients with disease control in the real world is lower compared with clinical trials.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalJournal of Immunotherapy
Issue number5
Publication statusPublished - 1 Jun 2023

Bibliographical note

Funding Information:
For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing Foundation received a start-up grant from the governmental organization The Netherlands Organization 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 the funding of DMTR in 2019. For this work no funding was granted.

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.


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