MDS-065 Fatalities from Tumor Lysis Syndrome (TLS) After Anti-Hyperuricemic Monotherapy – Nationally Representative, Propensity Score Matched, Retrospective Study Comparison of Rasburicase and Allopurinol

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 22; pp. S302 - S303
• Main Authors: Cairo, Mitchell, EdD, Jack R. Gallagher, Barnes, Yvonne, Drea, Edward, Carrol, Susan
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2022
• Subjects: anti-hyperuricemic; hyperuricemia; liquid tumor; MSD; observational; propensity score; propensity score matching; PSM; retrospective; TLS; tumor lysis syndrome; observational; PS; liquid tumor; retrospective; PSM; HU; anti-hyperuricemic; hyperuricemia; propensity score matching; tumor lysis syndrome; TLS; MSD; propensity score
• DOI: 10.1016/S2152-2650(22)01393-3
• ISSN: 2152-2650

Context: This is the first US-representative, retrospective, real-world propensity score (PS) matching study comparing the occurrence of TLS-associated fatalities following allopurinol monotherapy versus rasburicase monotherapy. We have previously found rasburicase significantly and more rapidly reduces uric acid exposure (AUC) compared to allopurinol in patients with or at risk of TLS (Goldman/Cairo et al., Blood, 2001). Objective: To determine if a significant difference exists in the proportion of TLS-associated fatalities following treatment with allopurinol or rasburicase monotherapy for having or being at risk of TLS. Design: 282 rasburicase and allopurinol patients were PS-matched for TLS risk using eleven predictive covariates. Patients were matched 1:1 using calipers of width equal to 0.2 of the standard deviation of the logit of the PS (d score). The overall PS logit was almost 0.6 before matching but near 0.0 afterward; covariates exhibited only a small imbalance (|d|<0 .25), indicating patients were well matched. Setting: Anonymized patient information from our 2021 physician-based, blinded, retrospective study, provided by 266 oncologists from US physician-owned practices, academic and non-academic hospitals, and outpatient clinics. Patients: Fielded June-September, the 2021 study included 715 randomized liquid-tumor patients treated in the past year for hyperuricemia (HU) risk and TLS potential. The 2022 PSM analysis included only those receiving rasburicase or allopurinol monotherapy and excluded patients with spontaneous TLS or TLS before HU treatment, leaving 533 potential subjects. 282 were matched on PS and eleven pre-HU treatment covariates: acute renal failure, age, anti-cancer regimen, creatinine, gender, lactate dehydrogenase, perceived risk, renal disease, tumor type, uric acid, and white blood count. Unmatched cases were discarded. Main Outcomes Measure: Proportions of mortalities that physicians said were the direct result of TLS. The null hypothesis before matching was no significant difference between the groups. Results: Analyzing all matched patients (n=141 in each group), regardless of TLS development following HU treatment, TLS-associated mortality was significantly less likely among rasburicase patients (2.1% vs. 7.1% [P-value 0.047]). Analyzing the subset who developed TLS after HU treatment, TLS-associated fatalities were even less likely among rasburicase patients, 3 of 36 rasburicase vs. 10 of 27 allopurinol patients [P-value 0.005]. Conclusions: Results indicate rasburicase compared to allopurinol significantly reduces TLS-associated fatalities.