Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma
Related Experiment Video
Updated: Feb 4, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Rodabe N Amaria1, Sangeetha M Reddy2, Hussein A Tawbi1
1Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
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.
Insights
Neoadjuvant immune checkpoint blockade shows promise for melanoma treatment. Combined ipilimumab and nivolumab offer high response rates but with significant toxicity, while nivolumab monotherapy provides modest responses with lower toxicity.
Area of Science:
- Oncology
- Immunology
- Clinical Trials
Background:
- Preclinical data suggest neoadjuvant immune checkpoint blockade enhances survival and T cell responses in melanoma.
- Optimal neoadjuvant regimens for resectable melanoma remain undefined.
Purpose of the Study:
- To evaluate neoadjuvant nivolumab versus combined ipilimumab and nivolumab in high-risk resectable melanoma.
- To assess response rates, toxicity, and immune correlates of these neoadjuvant immunotherapies.
Main Methods:
- A randomized phase 2 study (NCT02519322) involving 23 patients with high-risk resectable melanoma.
- Assessment of RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs), and immune correlates.
Main Results:
- Combined ipilimumab and nivolumab demonstrated high response rates (ORR 73%, pCR 45%) but significant toxicity (73% grade 3 trAEs).
- Nivolumab monotherapy showed modest responses (ORR 25%, pCR 25%) with low toxicity (8% grade 3 trAEs).
- Responders exhibited higher lymphoid infiltrates; nivolumab responders showed more clonal and diverse T cell infiltrates.
Conclusions:
- Neoadjuvant immune checkpoint blockade is feasible in melanoma.
- Further studies are needed to optimize treatment regimens and validate biomarkers for neoadjuvant immunotherapy in melanoma.
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