Artificial intelligence-enabled screening strategy for drug repurposing in monoclonal gammopathy of undetermined significance

Alexander J. Ryu, Shaji Kumar, Angela Dispenzieri, Robert A. Kyle, S. Vincent Rajkumar, Thomas C. Kingsley

Research output: Contribution to journalArticlepeer-review

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a benign hematological condition with the potential to progress to malignant conditions including multiple myeloma and Waldenstrom macroglobulinemia. Medications that modify progression risk have yet to be identified. To investigate, we leveraged machine-learning and electronic health record (EHR) data to screen for drug repurposing candidates. We extracted clinical and laboratory data from a manually curated MGUS database, containing 16,752 MGUS patients diagnosed from January 1, 2000 through December 31, 2021, prospectively maintained at Mayo Clinic. We merged this with comorbidity and medication data from the EHR. Medications were mapped to 21 drug classes of interest. The XGBoost module was then used to train a primary Cox survival model; sensitivity analyses were also performed limiting the study group to those with non-IgM MGUS and those with M-spikes >0.3 g/dl. The impact of explanatory features was quantified as hazard ratios after generating distributions using bootstrapping. Medication data were available for 12,253 patients; those without medications data were excluded. Our model achieved a good fit of the data with inverse probability of censoring weights concordance index of 0.883. The presence of multivitamins, immunosuppression, non-coronary NSAIDS, proton pump inhibitors, vitamin D supplementation, opioids, statins and beta-blockers were associated with significantly lower hazard ratio for MGUS progression in our primary model; multivitamins and non-coronary NSAIDs remained significant across both sensitivity analyses. This work could inform subsequent prospective studies, or similar studies in other disease states.

Original languageEnglish (US)
Article number28
JournalBlood cancer journal
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint

Dive into the research topics of 'Artificial intelligence-enabled screening strategy for drug repurposing in monoclonal gammopathy of undetermined significance'. Together they form a unique fingerprint.

Cite this