Robust prediction of patient outcomes with immune checkpoint blockade therapy for cancer using common clinical, pathologic, and genomic features

Despite the revolutionary impact of immune checkpoint blockade (ICB) in cancer treatment, accurately predicting patient responses remains elusive. We analyzed eight cohorts of 2881 ICB-treated patients across 18 solid tumor types, the largest dataset to date, examining diverse clinical, pathologic, and genomic features. We developed the LOgistic Regression-based Immunotherapy-response Score (LORIS) using a transparent, compact 6-feature logistic regression model. LORIS outperforms previous signatures in ICB response prediction and can identify responsive patients, even those with low tumor mutational burden or tumor PD-L1 expression. Importantly, LORIS consistently predicts both objective responses and short-term and long-term survival across most cancer types. Moreover, LORIS showcases a near-monotonic relationship with ICB response probability and patient survival, enabling more precise patient stratification across the board. As our method is accurate, interpretable, and only utilizes a few readily measurable features, we anticipate it will help improve clinical decision-making practices in precision medicine to maximize patient benefit. ### Competing Interest Statement E.R. is a co-founder of MedAware, Metabomed and Pangea Biomed (divested), and an unpaid member of Pangea Biomed's scientific advisory board. L.G.T.M. is listed as an inventor on intellectual property owned by Memorial Sloan Kettering Cancer Center related to the use of TMB in cancer immunotherapy, unrelated to this work. The other authors have no competing interests.