Improving conventional prognosticators in diffuse large B cell lymphoma using marker ratios

Risk stratification for diffuse large B-cell lymphoma (DLBCL) is required as patients with disease may not be cured despite initial R-CHOP treatment. We investigated gene ratio tests to predict survival outcome of DLBCL patients based on the relationship between immune-effector and inhibitory (checkpoint) genes from nanoString™ nCounter in 158 paraffin-embedded DLBCL tissues. We assessed the predictive value of several possible gene ratios using a tree-based survival statistical model, and investigated the predictive value of those gene ratios in an independent R-CHOP treated cohorts of 233 patients. We showed that an immune ratio composed of CD4∗CD8∗:(CD163/CD68)∗PD-L1 was able to stratify overall survival better than single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO) and has potential implications for selection of patients for checkpoint-blockade within clinical trials.