Abstract: Introduction: HDMTX (dose > 1 g/m²) is used commonly as a treatment for high-grade lymphomas, ALL and sarcomas. Glucarpidase is available for urgent treatment of MTX-induced renal dysfunction, in patients with toxic plasma MTX levels, at risk of life threatening complications. Pharmacist peer discussion nationally, highlighted a recent requirement for glucarpidase in overweight adult patients, prompting this study. Aims and objectives: Primary objective: To investigate associations between high BMI and requirement for glucarpidase, a proxy measure for severe toxicity. Secondary objective: to examine national variation in glucarpidase dosing in patients with raised BMI. Methodology: We developed two cohorts to achieve our objectives: Cohort 1. Retrospective review of UK adult patients receiving glucarpidase between 01 January 2019 and 01 July 2021, identified via UK sales. A data collection form was developed and piloted, and hospitals having placed orders were invited to participate. Patient baseline demographics, clinical characteristics, MTX regimen/ dose and interacting medicines were collated. The glucarpidase dose calculation method and toxicity outcome were recorded. Cohort 2: A control group from three participating centres of all patients that received HDMTX, not requiring glucarpidase, during the same period. BMI was categorised according to WHO definitions for overweight and obesity; we described the % of patients in each category and BMI distributions. BMIs across the two cohorts were compared using an unpaired t-test. Results: 23/24 Adult Treatment Centres completed data collection on 34 patients – 32 patients received glucarpidase, and two orders were not administered. In the control group (N = 209), 61% had BMI > 25 kg/m², and 23%hadBMI > 30 kg/m² compared to 85% and 59% in the glucarpidase group respectively (p = < 0.0001). The BMI average of the control group was 26.9 kg/m², compared to 31.6 kg/m² in the glucarpidase-treated group. 29/32 patients received glucarpidase dosed according to total body weight (TBW), and three patients according to adjusted body weight (ABW40). Discussion: Full weight-based chemotherapy dosing is recommended practice for treating obese patients with cancer, especially with curative intent.1 Only four out of 20 patients with BMI ≥ 30 in the glucarpidase cohort did not receive TBW dose methotrexate, when the reason for dose modification was stated as obesity. There is a known association between obesity and risk of haematological malignancy, particularly DLBCL,2 however this small case series suggests obese patients are overly represented in the HDMTX UK patient population experiencing the most severe toxicity, proposing a significant association but not causation. One study has shown an association between overweight patients and increased serum creatinine post-HDMTX,3 conversely another showed no association between obesity and delayed MTX clearance.4 Study limitations and areas of further investigation: Further work is required, using a larger dataset, to determine if obesity is an independent risk factor for MTX-induced renal dysfunction and delayed clearance. Study outcomes are complicated by the fact the precise indication for glucarpidase is ambiguous. In our study, all three patients receiving glucarpidase dosed according to ABW40 successfully cleared methotrexate, a renal function returning to baseline, supported by published literature on the use of lower doses5 – an approach which may reduce treatment costs. Larger patient numbers are required to further investigate the optimal dose. [ABSTRACT FROM AUTHOR]
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