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TMB Biomarker — SCE Medical Oncology MCQ

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ModerateLung CancerTMB BiomarkerSCE Medical Oncology

A 60-year-old man with NSCLC has a tissue-based next-generation sequencing (NGS) panel performed. The report shows tumour mutational burden (TMB) of 15 mutations per megabase. PD-L1 TPS is 10%. What is the role of TMB as a biomarker for immunotherapy?

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Correct answer: B — TMB is an imperfect predictor of ICI benefit; high TMB (≥10 mut/Mb) has a tissue-agnostic FDA approval for pembrolizumab (KEYNOTE-158) but is NOT used as a primary biomarker for first-line NSCLC ICI decisions in the UK — PD-L1 remains the standard predictive biomarker

While TMB has biological rationale as an ICI biomarker (more mutations → more neoantigens → better immune recognition), its clinical utility is debated. TMB-high (≥10 mut/Mb) has a tissue-agnostic FDA approval (KEYNOTE-158) but is NOT endorsed by ESMO or NICE as a primary first-line ICI selection biomarker in NSCLC. PD-L1 TPS remains the standard. TMB limitations include: assay variability, no universal threshold, and imperfect correlation with ICI benefit. TMB is most useful in second-line/refractory settings for tumour-agnostic ICI consideration.

Reference: ESMO 2024 NSCLC/Precision Medicine; KEYNOTE-158 TMB; ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)