Major Pathological Response Linked to 98% 5-Year Survival With Neoadjuvant Immunotherapy in Melanoma

Patients with resectable stage IIIB-IV melanoma who achieved a major pathological response (MPR) after neoadjuvant immune checkpoint inhibitors (ICIs) had a 5-year overall survival (OS) rate of about 98%, according to an updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC) published in Nature Medicine.

The investigators described neoadjuvant ICIs as standard of care for resectable stage IIIB-D melanoma but noted knowledge gaps regarding optimal treatment type, long-term survival, postsurgical management, and patient subgroups. They analyzed participant-level data from 1,038 patients at 26 international sites, 72.7% treated in clinical trials and 27.3% outside trials. Patients received ICIs (n=735), BRAF and MEK inhibitors (BRAF/MEKis; n=119), or an ICI plus targeted therapy (n=184). Median follow-up was 2.6 years.

MPR rates were 57.8% with ICIs, 51.4% with BRAF/MEKis, and 44.6% with ICI plus targeted therapy. Anti-programmed cell death protein 1 (PD-1) therapy combined with another immuno-oncology agent produced a higher MPR rate than anti-PD-1 alone (61.4% vs 49.5%). Five-year recurrence-free survival (RFS) was 73.9% with combination immunotherapy, 61.0% with anti-PD-1 alone, and 37.4% with BRAF/MEKis; corresponding 5-year OS rates were 87.5%, 83.3%, and 69.8%. Among ICI-treated patients with MPR, 5-year OS was 98.8% with anti-PD-1 alone and 97.9% with combination therapy.

In ICI-treated patients with MPR, 5-year RFS was similar with or without adjuvant ICIs (90.8% vs 90.6%). The authors said this finding requires prospective investigation because adjuvant therapy was not randomly assigned. Neoadjuvant ICIs also showed activity in BRAF-mutant melanoma (MPR, 46.3%) and acral melanoma (MPR, 38.1%), although subgroup sizes varied.

Reported limitations included small subgroups and the absence of central histopathology or imaging review. The investigators concluded that neoadjuvant BRAF/MEKis "can be largely abandoned" and called for predictive biomarker-driven trials and effective adjuvant strategies for nonresponders.

Source: Long GV, Pires da Silva I, Perry KA, et al. Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC). Nat Med. Published online October 1, 2026. doi:10.1038/s41591-026-04677-z