Optimal Patient Selection for Immune-Therapies of Cancer Using Tissue Phenomics*
Guenter Schmidt, PhD
Vice President Research, Definiens AG
Current immune-therapies for advanced melanoma and lung cancer show impressive response rates and long-term survival. Approximately one of five patient lives is saved by modulating his immune system with the blockade of an immune checkpoint. On the other hand, four of five patients do not respond to a very expensive treatment which causes severe side effects, massively reduced quality of live, and delayed search for alternative therapies. Tissue Phenomics helps to select those patients with high accuracy which will benefit from the therapy on the basis of pre-treatment cancer tissue samples.
We present on how the Tissue Phenomics methodology is used to discover a novel companion diagnostic test for an immune-therapy for advanced stage III/IV cancer patients. The data was collected in the context of a clinical trial in which the clinical response (by RECIST measurement) and overall survival were recorded for each patient treated with the checkpoint inhibitor. Various subpopulation of T-cells were automatically identified by a robust and parameter-free image analysis solution in immunohistochemically stained tissue sections. Virtually multiplexed assays composed by co-registration of consecutive tissue sections enabled the measurement of spatial distributions and co-occurrences of those populations in the tumor region. The numerous measurements were mined for predictive performance in terms of positive predictive value, prevalence and Kaplan-Meier p-value. We discovered that the tumor-associated CD8 positive T-cell density provides a substantial contribution to a patient selection algorithm which achieves a therapy response classification accuracy of greater than 80% (Kaplan-Meier p-value < 0.05).
Tissue Phenomics accelerates tremendously the discovery of novel predictive tests in immune-oncology, as well as improving the accuracy in patient selection. This approach opens the door for a new generation of personalized immune-therapies for the benefit of the patient.