Cancer Immunol Immunother: Tumor Mutation Score (TMS) replaces Tumor Mutation Load (TMB) to predict the response of NSCLC patients to ICI treatment?

Immuno-checkpoint inhibitors (ICI) are becoming the latest technology in cancer treatment and have made a significant difference in the treatment of advanced cancer patients, especially non-small cell lung cancer (NSCLC).
, there is an urgent need for clinically useful biomarkers to identify patients who may benefit from ICI treatment.
, PD-L1 expression and tumor mutation load (TMB) have been approved by the FDA to predict NSCLC's response to immunotherapy.
TMB represents genomic instability and may trigger new antigens produced by cancer cell mutations to improve immunogenicity.
TMB evaluation is now expensive and has poor results, mainly through whole genome sequencing (WGS) or full exon sequencing (WES).
, the researchers developed a new tumor mutation score (TMS), defined as the number of genes for candidate gene mutations.
the study, the researchers compared TMS with TMB and PD-L1 in 240 NSCLC patients and validated it in 34 additional NSCLC patients.
18 genes and features associated with TMS18 were significantly associated with longer progressive lifetime (PFS) or better response.
researchers defined the number of mutant genes in the 18 beneficial genes as TMS18.
the predictions expressed by TMS18, TMB and PD-L1 are expressed in the survival analysis, the risk ratio of TMS18 (HR 0.307, P.lt;0.001) and The P values are both smaller than TMB (HR 0.455, P=0.004) and PD-L1 expression (HR 0.403, P=0.005).
addition, TMS18's AUC is significantly higher than TMB's, and combined with PD-L1 can further improve accuracy.
the general threshold of TMS18 can benefit more patients.
these findings are essentially consistent in the validation queue.
the predictive sensitivity of TMS18, TMB, and PD-L1 expressions, TMS18 is more effective than TMB in predicting the response of NSCLC patients to ICI treatment.
TMS is more feasible and economical than non-selective TMB.
combined with TMS18 and PD-L1 may be more accurate in predicting the efficacy of ICI treatment in NSCLC patients.