Leveraging pharmacovigilance data to predict population-scale toxicity profiles of checkpoint inhibitor immunotherapy.

Immune checkpoint inhibitor (ICI) therapies have made considerable advances in cancer immunotherapy, but the complex and diverse spectrum of ICI-induced toxicities poses substantial challenges to treatment outcomes and computational analysis. Here we introduce DySPred, a dynamic graph convolutional network-based deep learning framework, to map and predict the toxicity profiles of ICIs at the population level by leveraging large-scale real-world pharmacovigilance data. DySPred accurately predicts toxicity risks across diverse demographic cohorts and cancer types, demonstrating resilience in small-sample scenarios and revealing toxicity trends over time. Furthermore, DySPred consistently aligns the toxicity-safety profiles of small-molecule antineoplastic agents with their drug-induced transcriptional alterations. Our study provides a versatile methodology for population-level profiling of ICI-induced toxicities, enabling proactive toxicity monitoring and timely tailoring of treatment and intervention strategies in the advancement of cancer immunotherapy.