Figure 3.

Association between TMB and Efficacy in Multivariate Context

(A) Correlation between TMB and PD-L1 expression (Spearman ρ −0.087 [95% CI −0.32 to 0.16], p = 0.48). Patients with CR/PR (n = 24) are colored in blue circles; those with SD/PD (n = 51) are colored in gray squares.

(B) ROC curves for multivariate model correlation with objective response (CR/PR), with model including TMB (continuous variable), PD-L1 (continuous), histology (binary, squamous versus non-squamous), smoking status (binary, ever versus never), performance status (Eastern Cooperative Oncology Group [ECOG] 0 versus 1), and tumor burden (binary, > versus ≤ median) (plain line, AUC 0.869). Univariate correlation of TMB with objective response is shown again for reference (dotted line).

(C) ROC curves for univariate correlation of TMB (continuous) with progression-free survival (dotted line) at 6 months (purple, AUC = 0.585) or 12 months (yellow, AUC = 0.558). ROC curves for multivariate correlation of model including TMB (continuous), PD-L1 (continuous), histology (squamous versus non-squamous), smoking status (ever versus never), performance status (ECOG 0 versus 1), and tumor burden (binary, > versus ≤ median) also shown (plain lines; at 6 months AUC = 0.764, at 12 months AUC = 0.831).

(D) Histogram of objective response (CR/PR) to nivolumab plus ipilimumab in patients characterized by high mutation burden (>median TMB) and PD-L1 expression (≥1%), high mutation burden or PD-L1 expression, or neither. Response rates (n/N) are shown above each bar, with proportion of those with PR/CR colored in blue. Chi-square for trend p < 0.0001.

See also Figure S4.