Data from A Composite Decision Rule of CD8<sup>+</sup> T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials

Abstract

<div>AbstractPurpose:<p>To examine whether CD8<sup>+</sup> T-cell numbers in paired tumor biopsies in early-stage clinical trials can be used as an early indicator of clinical benefit for cancer immunotherapies.</p>Experimental Design:<p>Paraffin sections of tumor biopsies were stained immunohistochemically for CD8<sup>+</sup> T cells, which were digitally enumerated. The tumor biopsies were from cancer patients in early-phase trials testing novel immunotherapeutic agents. Paired biopsies taken before the start of treatment and on-treatment were compared. A total of 155 patients were used as the training set and an additional 221 patients were used as the validation set.</p>Results:<p>Using the Cox proportional hazard model, a ≥0.9- increase in fold change (FC) on a ln scale in CD8<sup>+</sup> T cells (corresponding to a 2.5-fold increase on the linear scale), from baseline, demonstrated a greater association with prolonged progression-free survival and allowed improved differentiation between groups above and below the threshold. Similarly, a ≥6.2 threshold in geometric mean of the on-treatment density (OTD) of T cells, which approximately corresponds to 500 cells/mm<sup>2</sup>, correlated with longer PFS. The combination of both criteria (FC and OTD) provided the best discrimination between clinically nonactive and active compounds.</p>Conclusions:<p>We propose that a composite score of CD8<sup>+</sup> T-cell density in paired biopsies taken before and on-treatment may be a new biomarker to inform on clinical outcomes in early immunotherapy clinical trials.</p></div>