Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

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.