Biomarkers For Predicting Checkpoint Inhibitor Response

As the biomarkers associating with the higher diagnosis for predicting the accurate responce to an anti-programmed cell death. But in this study the showing the different types of the biomarkers like interferon-gamma gene signature, and protien biomarkers. PD-L1 (programmed cell death ligand 1) immunohistochemistry (IHC), tumor mutational burden (TMB), gene expression profiling (GEP), and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) assays have been used to assess pretreatment tumor tissue to predict response to anti-PD-1/PD-L1 therapies.

However, the relative diagnostic performance of these modalities has yet to be established. these results could vary by tumor type, and as more studies become available, this aspect should be investigated. s that two of the most widely used biomarkers in current practice – PD-L1 immunohistochemistry (PD-L1IHC) and TMB – did not differ significantly in their ability to predict response to anti-PD-L1 immunotherapy.

Checkpoint inhibitor response

But the studies that examining the use of PD-L1IHC, TMB, gene expression profiling (GEP), and mIHC/IF assays to determine objective response to anti-PD-1/PD-L1 therapy. For PD-L1 IHC, only clinical trials that resulted in US Food and Drug Administration approval of indications for anti-PD-1/PD-L1 were including. Outcome measures for each assay modality included summary receiver operating characteristic (sROC) curves; their associated area under the curve (AUC); and pooled sensitivity, specificity, positive and negative predictive values (PPV, NPV), and positive and negative likelihood ratios (LR+ and LR−).

When each modality was evaluating with sROC curves, mIHC/IF had a significantly higher AUC (0.79) comparing with PD-L1 IHC (0.65), GEP (0.65,), and TMB (0.69). All modalities demonstrated comparable NPV and LR−; however, mIHC/IF demonstrated higher PPV (0.63) and LR+ (2.86) than the other approaches.

Primary statistical analysis

An in-depth analysis of the studies that supported this publication would show that the fewest number of patients studied had their tumors tested using the same technology; that is purporting to have a slight advantage. The authors do point out that the primary statistical analysis of ‘area under the curve’ for this meta-analysis; was weighting by number of patients studying for each methodology. Given that thousands of patients have been tested by PD-L1 IHC, which was inferior to multiplex IHC/immunofluorescence; where less than a few hundred patients have been studied; it will be interesting to see if this observation holds up with further study.

This study very likely reflects the general phenomenon; that studies with low power have a larger chance of having a larger effect size than studies with high power;  For PD-L1 IHC, only clinical trials that resulted in US Food and Drug Administration approval of indications; for anti–PD-1/PD-L1 were including. Studies combining more than 1 modality were also including. Preferring Reporting Items for Systematic Reviews and Meta-analysis guidelines were following.