Predictive impact of tumor mutational burden on real-world outcomes of first-line ICIs in metastatic melanoma: database analysis

The choice of threshold and reliability of high tumor mutational burden (TMB) to predict outcomes and guide regimen choice for patients with metastatic melanoma receiving first-line immune checkpoint inhibitors in the real world is not well known. Analysis of a USA nationwide database identified 497 metastatic melanoma patients who received first-line anti-PD-1 monotherapy (n=240) or dual anti-PD-1 and anti-CTLA-4 therapy (n=257). TMB was high (≥ 10 mut/Mb) in 352 patiënten (71%). Both in the monotherapy group and in the dual therapy group, high TMB predicted superior real-world PFS and OS. Dual ICI offered no significant advantage in BRAF-wildype patients and demonstrated greatest benefit in the TMB 10-19 mut/Mb group, identifying a TMB-very high (≥20 mut/Mb) BRAF-mutated patient subgroup for whom ICI monotherapy may be preferable. The authors conclude that high TMB predicts superior outcomes with first-line ICIs for metastatic melanoma, while coassessment of BRAF status and TMB may inform first-line regimen choice.