Monitoring peripheral blood data supports the prediction of immunotherapy response in advanced non-small cell lung...

The identification of non-small cell lung cancer (NSCLC) patients who will benefit from immunotherapy remains a clinical challenge. Monitoring real-world data (RWD) in the first cycles of therapy may provide a more accurate representation of response patterns in a real-world setting. We propose a multivariate Bayesian joint model using generalized linear mixed effects, trained and validated on RWD from 424 advanced NSCLC patients retrospectively collected from three clinical centers. Center1 was used as training ( $N=212$ ), while Center2 and Center3 were used as independent testing sets ( $N=137$ and $N=75$ , respectively). Peripheral blood data (PBD) were collected at baseline and at three follow-up time points, alongside demographic and epidemiologic features. Six models were trained to predict progression-free survival at 6 months, PFS(6), using different number of longitudinal samples (baseline, two, or four time points) of the neutrophil-to-lymphocyte ratio (NLR) or a multivariate feature selection. Long-term predictions at 12 and 24 months were also evaluated. Prediction accuracy was measured using the area under the receiver operating characteristic curve (AUC). The proposed model significantly improved prediction performance, achieving AUCs of 0.870, 0.804 and 0.827 at 6, 12 and 24 months for Center2, and 0.824, 0.822 and 0.667 for Center3. There was also a significant difference in PFS and overall survival (OS) between predicted response groups, defined by a 6-month PFS cutoff (log-rank test $p<0.001$ ). Our study suggests that the integration of multiple biomarkers and monitored PBD in an RWD-based Bayesian joint model framework significantly improves immunotherapy response prediction in advanced NSCLC compared to conventional approaches involving biomarker data at baseline only.