Outcomes in Patients With Multiple Myeloma and Prescribed Urate-Lowering Therapy: A Propensity-Matched Study

Introduction Multiple myeloma or MM is a plasma cell dyscrasia that causes monoclonal immunoglobulin accumulation and is associated with manifestations including hypercalcemia, anemia, bone pain, and renal dysfunction. Gout is also associated with electrolyte derangements that result in similar end-organ dysfunction. There is little information on outcomes in patients with both diagnoses. Methods Adult patients with MM were propensity-score matched according to age at index event, sex, demographics, and comorbidities. Patients were identified using the International Classification of Diseases (ICD)-10 codes through TriNetX's US Collaborative Network and sorted into cohorts based on the prescription of urate-lowering therapies (ULTs). Three ULTs, allopurinol, febuxostat, and rasburicase, were studied individually. Cohorts of patients with MM and any ULT and those with MM but no ULT were also included. Outcomes were followed for five years to assess the rates of acute kidney injury (AKI), dialysis initiation (HD), seizures, atrial fibrillation/atrial flutter (AF/AFL), ventricular fibrillation/ventricular tachycardia (VF/VT), and all-cause mortality.  Results When compared to patients with MM with any ULT, the cohort of patients with MM and no ULT demonstrated significantly lower rates of HD (HR 0.74, 95% CI 0.671-0.815, p<0.0001), AF/AFL (HR 0.99, 95% CI 0.924-1.061, p<0.0001), VF/VT (HR 0.853, 95% CI 0.752-0.968, p=0.0066), and mortality (HR 1.012, 95% CI 0.965-1.065, p<0.0001). The MM with no allopurinol group demonstrated significantly reduced rates of AKI (HR 0.901, 95% CI 0.839-0.968, p=0.0007), HD (HR 0.715, 95% CI 0.633-0.807, p<0.0001), seizures (HR 1.029, 95% CI 0.868-1.219, p=0.0012), AF/AFL (HR 1.006, 95% CI 0.921-1.098, p<0.0001), VF/VT (HR 0.837, 95% CI 0.718-0.975, p=0.0024), and mortality (HR 0.919, 95% CI 0.868-0.974, p<0.0001) compared to the MM with allopurinol cohort. The MM with no febuxostat cohort showed significantly reduced rates of AF/AFL (HR 1.009, 95% CI 0.762-1.335, p=0.004) compared to the MM cohort with febuxostat. The MM with no rasburicase cohort had significantly reduced risk of AF/AFL (HR 0.861, 95% CI 0.582-1.275, p=0.0381) compared to the MM with rasburicase cohort.  Conclusion ULTs may increase the risk of requiring HD, developing cardiac arrhythmia, and potentially mortality in patients with MM. There appear to be some ULT-specific relationships that warrant further exploration. These findings could be related to the electrolyte disturbances and end-organ dysfunction of MM being compounded by those of gout. Further research should be conducted to elucidate any relationship between these diagnoses.