Predictive factors for delayed high-dose methotrexate elimination: A practical issue for diffuse large B-cell lymphoma patients

Abstract

PurposeThe high-dose methotrexate (HD-MTX) regimen (>1 g/m²) is the standard of care for preventing and managing central nervous system (CNS) invasion in diffuse large B-cell lymphoma (DLBCL). Delayed elimination of HD-MTX can lead to severe toxicity. Albumin is a suggested biological marker to predict delayed elimination. This study aims to evaluate whether serum albumin can be used as a predictive factor.MethodsThis retrospective bicentric study includes DLBCL patients, receiving HD-MTX from 06.30.2016 to 12.31.2023 using CHIMI0v5.9. Data collected included demographic, biological, clinical and therapeutic. Eligible patients were over 18 years, with DLBCL diagnosis, available serum albumin before HD-MTX, with therapeutic drug monitoring of plasma methotrexate available. Univariate and multivariate analysis compared patients with and without delayed elimination.ResultsA total of 68 patients were included, with 15 suffering delayed elimination. Univariate analysis showed that male and Body Surface Area ≥ 2 m² (BSA) patients were more likely to have delayed clearance (respectively p = 0.01; p = 0.05). The association with male sex was confirmed in multivariate analysis (p = 0.01). Most cases of hypoalbuminemia were classified as grade 1 or 2. Patients with hypoalbuminemia received lower doses of MTX. Serum albumin level was not significantly associated with delayed elimination (p = 0.8).ConclusionsOverall, mainly biometric factors are associated with delayed elimination, highlighting the problem of prescribing habits based on body surface area. Albuminemia's role remains debated, and this study does not provide a conclusion, as patients with hypoalbuminemia received lower HD-MTX doses. Studies should account factors related to inflammation, nutrition and specific biomarkers (prealbumin).

Keywords: Methotrexate; hypoalbuminemia; lymphoma.