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Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

We conducted a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322) and assessed clinical responses and immune correlates. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST overall response rate 73%, pathologic complete response rate 45%) but substantial toxicity (73% grade 3 treatment related adverse events), whereas treatment with nivolumab monotherapy yielded modest responses (RECIST overall response rate 25%, pathologic complete response rate 25%) and low toxicity (8% grade 3 treatment related adverse events). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. Mutational load was also higher in responders to therapy.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001004352 Illumina HiSeq 2500 30
EGAD00001005803 unspecified 39
EGAD00010001608 MiSeq 59
Publications Citations
Publisher Correction: Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.
Nat Med 24: 2018 1942
6
neoepiscope improves neoepitope prediction with multivariant phasing.
Bioinformatics 36: 2020 713-720
17
B cells and tertiary lymphoid structures promote immunotherapy response.
Nature 577: 2020 549-555
1169
Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma.
Nat Commun 11: 2020 853
18
Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy.
Nat Cancer 1: 2020 210-221
116
Burden of tumor mutations, neoepitopes, and other variants are weak predictors of cancer immunotherapy response and overall survival.
Genome Med 12: 2020 33
50
The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.
Nat Commun 12: 2021 4098
81
Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment.
Cell 184: 2021 5338-5356.e21
197