The total number of mutations present in a tumor (mutation burden) appears to correlate with response to immune checkpoint inhibitors (both with combination ipilimumab and nivolumab, and single-agent anti-PD-1 agents) in melanoma and other cancers.

Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab...Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8+ T cells and IFNγ-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value.

Among 81 patients enrolled, 25 of them received palliative immunotherapy including anti-PD-1 antibody (pembrolizumab or nivolumab), anti-CTLA4 antibody (ipilimumab) monotherapy or combinations….Patients with TMB > 15 mut/Mb had a significantly longer PFS than patients with TMB ≤ 15 mut/Mb (p = 0.049) (Fig. 4b). High TMB was associated with improved PFS.

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies...High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-γ score/high TMB...