Brief Bioinform. 2026 Sep 1;27(5):bbag475. doi: 10.1093/bib/bbag475.
ABSTRACT
Prognostic stratification in multiple myeloma (MM) relies on staging systems fixed at diagnosis, discarding temporal information accumulated during treatment. We developed a dynamic multimodal framework that predicts residual overall survival from observation windows of 1-18 months post-diagnosis. The model integrates DeepInsight-transformed gene expression, longitudinal trajectories of 10 laboratory analytes, and treatment history through missingness-aware gated fusion. On the Multiple Myeloma Research Foundation (MMRF) cohort from the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile (CoMMpass) study (n = 752), five-fold-specific models trained on the development dataset achieved a mean concordance index (C-index) of 0.773 ± 0.024 and 1-year time-dependent area under the receiver operating characteristic curve (AUC) of 0.789 ± 0.021 on a common held-out CoMMpass validation split, outperforming the evaluated survival-learning baselines including DeepSurv, a Cox proportional hazards neural network, and random survival forests. Kaplan-Meier stratification showed significant separation at all primary landmarks (log-rank $P<.001$, hazard ratios 3.46-3.93). A distilled student model retaining only the DeepInsight gene expression representation and five baseline clinical features transferred to an independent microarray cohort (GSE24080, n = 507) without retraining, achieving a C-index of 0.672 and a time-dependent AUC at 1-year of 0.740, supporting cross-cohort transferability in a reduced-input setting. Interpretability analyses recovered ubiquitin-proteasome, endoplasmic reticulum (ER) stress, and Interferon Alpha Response signals consistent with established myeloma biology. These findings support the potential of dynamic multimodal modeling for longitudinal prognostic assessment in MM.
PMID:42704271 | DOI:10.1093/bib/bbag475