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Lung cancers with more mutations, typically those caused by smoking, were more likely to respond to pembrolizumab, the study that established tumour mutational burden as a biomarker for immunotherapy.
Rizvi, Hellmann, Snyder and colleagues at Memorial Sloan Kettering sequenced the exomes of non-small-cell lung cancers from patients treated with pembrolizumab in a discovery cohort of 16 and a validation cohort of 18. A higher number of nonsynonymous mutations was associated with a higher response rate, more durable clinical benefit and longer progression-free survival. A molecular smoking signature, a higher predicted neoantigen burden and mutations in DNA repair genes also tracked with benefit, and in one responder the team detected T cells recognising a specific neoantigen.
This paper turned a hypothesis into a biomarker: tumour mutational burden is now measured by commercial panels and underpins the tissue-agnostic approval of pembrolizumab for TMB-high tumours. It also explains why smokers' lung cancers, long the hardest to treat, respond better to immunotherapy than never-smokers' cancers.
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), Neoantigen, The cancer-immunity cycle.
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), Neoantigen, The cancer-immunity cycle.
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), Tumour mutational burden (TMB), PD-1 / PD-L1 immune checkpoint & T-cell activation.
Shares Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge, Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Tumour mutational burden (TMB), Memorial Sloan Kettering Cancer Center.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), Tumour mutational burden (TMB), PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-L1.