AI-supported modified risk staging for multiple myeloma cancer useful in real-world scenario

Introduction: : An efficient readily employable risk prognostication method is desirable for MM in settings where genomics tests cannot be performed owing to geographical/economical constraints. In this work, a new Modified Risk Staging (MRS) has been proposed for newly diagnosed Multiple Myeloma (NDMM) that exploits six easy-toacquire clinical parameters i.e. age, albumin, 132-microglobulin (132M), calcium, estimated glomerular filtration rate (eGFR) and hemoglobin. Materials and Methods: : MRS was designed using a training cohort of 716 NDMM patients of our inhouse MM Indian (MMIn) cohort and validated on MMIn (n=354) cohort and MMRF (n=900) cohort. K-adaptive partitioning (KAP) was used to find new thresholds for the parameters. Risk staging rules, obtained via training a J48 classifier, were used to build MRS. Results: : New thresholds were identified for albumin (3.6 g/dL), 132M (4.8 mg/L), calcium (11.13 mg/dL), eGFR (48.1 mL/min), and hemoglobin (12.3 g/dL) using KAP on the MMIn dataset. On the MMIn dataset, MRS outperformed ISS for OS prediction in terms of C-index, hazard ratios, and its corresponding p-values, but performs comparable in prediction of PFS. On both MMIn and MMRF datasets, MRS performed better than RISS in terms of C-index and p-values. A simple online tool was also designed to allow automated calculation of MRS based on the values of the parameters. Discussion: : Our proposed ML-derived yet simple staging system, MRS, although does not employ genetic features, outperforms RISS as confirmed by better separability in KM survival curves and higher values of C-index on both MMIn and MMRF datasets. Funding: : Grant: BT/MED/30/SP11006/2015 (Department of Biotechnology, Govt. of India), Grant: DST/ICPS/ CPS-Individual/2018/279(G) (Department of Science and Technology, Govt. of India), UGC-Senior Research Fellowship.