Multiple Myeloma DREAM Challenge Reveals Epigenetic Regulator PHF19 As Marker of Aggressive Disease

While the past decade has seen meaningful improvements in clinical outcomes for multiple myelomapatients, a subset of patients do not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involve assaying many genes making them difficult to implement. We organized the Multiple MyelomaDREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post challenge analysis identified a novel expression-based risk marker and histone modifier, PHF19, which featured prominently in several independent models. Lastly, we show that a simple four feature predictor composed of age, International Staging System stage (ISS), and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.