Clinical updates in neoadjuvant immunotherapy for melanoma before surgery

Locoregionally advanced melanoma represents a large group of high-risk melanoma patients at presentation and poses major challenges in relation to management and the risks of relapse and death.

Melanoma systemic therapy has undergone substantial advancements with the advent of immune checkpoint inhibitors and molecularly targeted therapies, which have been translated to the neoadjuvant setting for the management of locoregionally advanced disease. Notably, PD1 blockade as monotherapy, in combination with CTLA4 blockade or LAG3 inhibition, has demonstrated significant progress in reducing the risk of relapse and mortality, attributed to high pathologic response rates. Likewise, BRAF-MEK inhibition for BRAF mutant melanoma has yielded comparable outcomes, albeit with lower response durability than immunotherapy. Localized intralesional therapies such as Talimogene laherparepvec (T-VEC) and Tavokinogene Telseplasmid (TAVO) electro-gene-transfer combined with anti-PD1 have demonstrated favorable pathologic responses and increased immune activation. Most importantly, the S1801 randomized trial has demonstrated for the first time the advantage of the neoadjuvant approach over standard surgery followed by adjuvant therapy.

Current evidence supports neoadjuvant therapy as a standard of care for locoregionally advanced melanoma. Ongoing research will define the optimal regimens and the biomarkers of therapeutic predictive and prognostic value.