Patients Receiving Rasburicase for Treatment and Prophylaxis of Tumor Lysis Syndrome Are Under-Tested for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: A Single Center Retrospective Analysis

Introduction:

Tumor lysis syndrome (TLS) is an oncologic emergency caused by massive lysis of tumor cells, either with treatment or spontaneously resulting in release of large amounts of electrolytes and nucleic acids into the systemic circulation, which may result in complications such as acute kidney injury, seizures, and cardiac arrhythmias. Rasburicase, a recombinant urate oxidase, is a first line agent used in the management and prevention of TLS in high-risk patients. However, the use of rasburicase is contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, due to the risk of potentially life-threatening hemolysis. The Food and Drug Safety Authority (FDA) recommends that individuals at higher risk for G6PD deficiency should be screened before initiation of rasburicase therapy. A high prevalence of G6PD deficiency is noted in persons of African, Asian, and Mediterranean descent, making them prone to developing methemoglobinemia and hemolytic anemia with exposure to Rasburicase. We sought to study the adherence to best practice involving G6PD testing in patients treated with Rasburicase.

Methods: This retrospective study was conducted to identify patients who were administered rasburicase for treatment or prophylaxis of TLS at our tertiary care academic institution between 2011 and 2022. Data was extracted and analyzed for baseline parameters, indications for rasburicase and relevant laboratory investigations. We intended to study the practice for G6PD testing in patients at high risk for G6PD deficiency anemia with rasburicase. SAS v9.4 (Cary, NC) was used for statistical analysis.

Results: A total of 110 patients were included for analysis, out of which, 56% were males and 44% females. The median age was 63 years (IQR 57,71) and patients were predominantly African Americans (65/110, 59%), followed by Caucasians (44/110, 40%) and Hispanics (1/110, 0.1%). A total of 28/110 (25%) patients were treated at the medical intensive care unit, whereas the remaining were managed on inpatient medical wards (82/110, 74%). Acute myeloid leukemia (33/110,30%) was the most common underlying malignancy. 68/110 (61%) patients received rasburicase for TLS prophylaxis while 42/110 (38%) received the drug for the treatment of TLS. Uric acid levels on presentation ranged from 7 to 20.2 mg/dl with a median of 11.2 mg/dl (IQR 8.4,13.5). Majority of the patients had renal insufficiency on presentation (109/110, 99%), while only 13/110 (12%) patients required hemodialysis.

Rasburicase was ordered for administration most commonly by hematologists (54/110, 49%), followed by internal medicine (32/110,29%) and critical care physicians (24/110, 22%). Most patients (101/110, 92%) received a 6 mg dose of rasburicase per protocol. On retrospective review, G6PD testing was found to be indicated in 67/110 (60%) patients (due to African American ethnicity), out of which only 18% (12/67) patients were tested for G6PD before the administration of rasburicase. G6PD levels were noted to be normal or elevated in all (18/18,100%) of the patients tested.

Conclusion: Our analysis showed that a significantly low number of patients (18%) out of all the candidates for G6PD testing prior to administration of rasburicase were tested in practice. Practices to promote G6PD testing in candidate patients, such as physician education (especially non-hematologists) or enforcing hard stops on the electronic medical record are needed to improve rates of G6PD testing and prevent potentially fatal hemolysis in these patients. The testing was also not likely performed due to the delay in obtaining results which may can help guide decision making to administer rasburicase and it may be beneficial to have inhouse testing in facilities who treat populations predisposed to G6PD deficiency.

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