Effectiveness of rasburicase 4.5 mg in the treatment of tumor lysis syndrome-related hyperuricemia

Abstract

Purpose: Optimal rasburicase dosing remains unknown. This study evaluated outcomes of single rasburicase 4.5 mg doses when treating moderate (12 to <15 mg/dL) versus high (≥15 mg/dL) uric acid (UA) levels.

Methods: This retrospective observational cohort study included patients with an active malignancy and tumor lysis syndrome (TLS) who received rasburicase 4.5 mg. Patients were categorized by UA levels before administration of rasburicase. The primary outcome was UA normalization (<8 mg/dL) 24 hours post rasburicase administration. Secondary outcomes included repeat rasburicase dose(s) within 72 hours and renal replacement therapy (RRT) within 7 days. Nominal and continuous data were analyzed using chi squared or Fisher's exact and Wilcoxon rank-sum or Student's t test, respectively. Multivariate regression analysis explored risk factors for continued hyperuricemia.

Results: After screening of 428 patients, 124 moderate and 95 high baseline UA values were included. Overall, baseline characteristics were similar between cohorts. The primary outcome was achieved more often in the moderate cohort (92.7% vs 67.4% [P < 0.001]). More high cohort patients received repeat rasburicase doses (8.1% vs 21.1% [P = 0.009]) with no difference in RRT frequency. Risk factors for continued hyperuricemia included baseline UA, potassium and body mass index.

Conclusion: A single dose of rasburicase 4.5 mg was less effective in achieving UA normalization in patients with a baseline UA of ≥15 mg/dL vs 12 to <15 mg/dL, without significant differences in patient-oriented outcomes such as RRT. Higher initial doses of rasburicase may be needed for patients with a baseline UA of ≥15 mg/dL. Additional studies are needed to determine optimal dosing for these patients.

Keywords: hyperuricemia; malignancy; rasburicase; tumor lysis syndrome; uric acid.