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

Background: 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.

Methods: 282 rasburicase and allopurinol patients (pts) were PS-matched for TLS risk using eleven predictive covariates. Pts 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 pts were well matched. 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. Fielded June-September, the 2021 study included 715 randomized liquid-tumor pts 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 pts 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.

Results: Analyzing all matched pts (n=141 in each group), regardless of TLS development following HU treatment, TLS-associated mortality was significantly less likely among rasburicase pts (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 pts, 3 of 36 rasburicase vs. 10 of 27 allopurinol pts [P-value 0.005]).

Conclusions: Results indicate rasburicase compared to allopurinol significantly reduces TLS-associated fatalities.

Cairo:Omeros: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Miltenyi: Research Funding; Merck: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; NEKTAR: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celularity: Research Funding. Gallagher:Clarity Pharma: Current Employment. Barnes:Sanofi: Current Employment, Current equity holder in publicly-traded company. Drea:Sanofi: Current Employment, Current equity holder in publicly-traded company. Carroll:Clarity Pharma: Current Employment.