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Tumour mutation score is a better predictor than TMB

WCLC 2019
Tumour mutation burden (TMB) is –after programmed death ligand 1 (PD-L1) expression– an intensively investigated biomarker for immune checkpoint inhibitors in patients with non-small-cell lung cancer (NSCLC). However, its efficiency is attenuated by mutations such as epidermal growth factor (EGFR), and testing still is not fully standardised and comparable. Li et al. developed a tumour mutation score (TMS) as a better biomarker to predict response to immune checkpoint inhibitors in patients with established NSCLC.

The development was done by defining TMS as the number of genes with nonsynonymous somatic mutations (TMS18 was TMS of 18 favourable genes, integer from 0 to 18). Mutations were detected by targeted next-generation sequencing in 240 NSCLC patients treated with anti-PD-(L)1 monotherapy or in combination with anti-CTLA4 treatment. Durable clinical benefit was defined as progression-free survival (PFS) ≥6 months. TMS, TMB, and PD-L1 expression were compared among patients with and without durable clinical benefit.

It was found that 12 genes in patients with durable clinical benefit and 11 genes in patients with no durable benefit were significantly associated with longer PFS and better response (5 sharing genes). Patients with durable clinical benefit had significantly higher TMS18 (P< 0.001), TMB (P=0.006), and PD-L1 expression (P=0.032). TMS18 significantly correlated with TMB.

Concerning PFS, the difference in TMS18 was more significant than TMB and PD-L1 expression, when comparing patients with durable clinical response versus patients with progressive disease. The area under the curves of TMS18 was also significantly greater than that of TMB. Furthermore, TMS18 was more powerful in distinguishing EGFR carriers from wild-type NSCLC patients. Thus, simple transformation from unselective TMB to selective TMS18 greatly enhances the power of mutation-based biomarkers, with TMS18 being a possible better predictive biomarker for immunotherapy in NSCLC than TMB [1].

  1. Li Y, et al. P2.04-40. WCLC 2019.


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