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Cited by 880Cancer Immunotherapy and BiomarkersCutaneous Melanoma Detection and ManagementImmunotherapy and Immune Responses

Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma

Blank, Christian U., Rozeman, Elisa A., Fanchi, Lorenzo F., Sikorska, Karolina, van de Wiel, Bart, Kvistborg, Pia, Krijgsman, Oscar, van den Braber, Marlous +16 more·2018·Nature Medicine
DOI 10.1038/s41591-018-0198-0
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Abstract

Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse-free survival of stage III melanoma patients 1,2. In stage IV disease, the combination of ipilimumab + nivolumab is superior to ipilimumab alone and also appears to be more effective than nivolumab monotherapy 3. Preclinical work suggests that neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy 4. To address this question and to test feasibility, 20 patients with palpable stage III melanoma were 1:1 randomized to receive ipilimumab 3 mg kg-1 and nivolumab 1 mg kg-1, as either four courses after surgery (adjuvant arm) or two courses before surgery and two courses postsurgery (neoadjuvant arm). Neoadjuvant therapy was feasible, with all patients undergoing surgery at the preplanned time point. However in both arms, 9/10 patients experienced one or more grade 3/4 adverse events. Pathological responses were achieved in 7/9 (78%) patients treated in the neoadjuvant arm. None of these patients have relapsed so far (median follow-up, 25.6 months). We found that neoadjuvant ipilimumab + nivolumab expand more tumor-resident T cell clones than adjuvant application. While neoadjuvant therapy appears promising, with the current regimen it induced high toxicity rates; therefore, it needs further investigation to preserve efficacy but reduce toxicity.

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Crossref · 10.1038/s41591-018-0198-0

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  • High B cell lineage scores in responders were replicated in an additional melanoma cohort (OpACIN-neo) treated with neoadjuvant versus adjuvant checkpoint blockade (n = 12 responders, 6 non-responders).

    “Findings of high B cell lineage scores in responders were replicated in samples from an additional cohort of patients with melanoma treated with neoadjuvant versus adjuvant checkpoint blockade (ClinicalTrials.gov identifier NCT02437279, OpACIN-neo trial) (n = 12 responders, 6 non-responders)35”

    From B cells and tertiary lymphoid structures promote immunotherapy response (2020) · cites this paper as [35]

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Authors
Blank, C. U., Rozeman, E. A., Fanchi, L. F., Sikorska, K., van de Wiel, B., Kvistborg, P., Krijgsman, O., van den Braber, M., Philips, D., Broeks, A., van Thienen, J. V., Mallo, H. A., Adriaansz, S., ter Meulen, S., Pronk, L. M., Grijpink-Ongering, L. G., Bruining, A., Gittelman, R. M., Warren, S., van Tinteren, H., Peeper, D. S., Haanen, J. B. A. G., van Akkooi, A. C. J., & Schumacher, T. N.
Affiliations
  • The Netherlands Cancer Institute (NL)
  • Adaptive Biotechnologies (United States) (US)
  • Nanostring Technologies (United States) (US)
Corresponding author
  • Blank, Christian U.
  • Schumacher, Ton N.
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2018-10-08
Volume
24
Issue
11
Pages
1655-1661
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-018-0198-0
OpenAlex
W2894796660
Cited by
880
References
32
Citations by year
2026: 63 · 2025: 93 · 2024: 125 · 2023: 147 · 2022: 110 · 2021: 125 · 2020: 127 · 2019: 75 · 2018: 10
FWCI
32.07
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Amgen
  • World Health Organization
  • Adaptive Biotechnologies
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
neoadjuvant immunotherapy, adjuvant immunotherapy, ipilimumab, nivolumab, CTLA-4 blockade, anti-PD-1 therapy, stage III melanoma, immune checkpoint inhibitors, tumor-infiltrating T cells, treatment-related adverse events, relapse-free survival
MeSH terms
Ipilimumab, Nivolumab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Humans, Male, Melanoma, Middle Aged, Neoplasm Staging, Chemotherapy, Adjuvant, Disease-Free Survival, Neoadjuvant Therapy, CTLA-4 Antigen

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