Neoadjuvant Immune Checkpoint Blockade in High-Risk Resectable Melanoma

By R. Amaria, S. Reddy, H. Tawbi, M. Davies, M. Ross, I. Glitza, J. Cormier, C. Lewis, W. Hwu, E. Hanna and 35 more. Nature Medicine, 2018

754 citations recorded by the source corpus.

Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment1; however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). 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. These results describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers. Neoadjuvant combination treatment with nivolumab and ipilimumab in patients with high-risk melanoma results in higher response rates than nivolumab monotherapy and warrants future optimization of dosing regimens to preserve efficacy while limiting toxicity.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/251ac2984307dc31d5a4596caa7a07c90195b1e8

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In Immunology

1. D. Pardoll
2. Janis Taube
3. S. Topalian
4. K. Flaherty
5. Aviv Regev
6. C. Blank
7. Lieping Chen
8. Antoni Ribas

In Oncology

1. D. Pardoll
2. Janis Taube
3. S. Topalian
4. K. Flaherty
5. C. Blank
6. Lieping Chen
7. J. Wolchok
8. Antoni Ribas

Citations in the corpus

• Neoadjuvant checkpoint blockade for cancer immunotherapy (2020, background): “†Anti–PD-1, nivolumab in (49) and pembrolizumab in (51).”
• Integrative molecular and clinical modeling of clinical outcomes to PD-1 blockade in metastatic melanoma patients (2019, positive): “…enriched in ipi-experienced responders) in ICB response, consistent with data from a recent trial demonstrating higher B-cell infiltrate in responders to neoadjuvant immunotherapy 48 , though the specific cell types, functional states, and tumor-immune interactions are not yet well characterized.”