Clinical characteristics associated with terminal methotrexate clearance in patients with non-Hodgkin lymphomas receiving high-dose methotrexate

IntroductionHigh-dose systemic methotrexate (HD-MTX) in doses ≥ 3 g/m² is the cornerstone of treatment for central nervous system (CNS) lymphomas and prophylaxis for patients with high-risk of CNS relapse. Its administration requires extensive supportive care until serum clearance is achieved. Risk factors for delayed methotrexate (MTX) clearance and renal injury are well-characterized and include baseline renal function, age, and hypoalbuminemia. Data assessing characteristics associated with slow terminal clearance are lacking.MethodsWe performed a single-center, retrospective cohort study between 1/2015 to 10/2023 to evaluate characteristics associated with the rate of MTX clearance in the 72 h after serum MTX levels decline to below 0.2 µmol/L in adult patients with lymphoma who received MTX at doses ≥ 3 g/m². MTX administration was evaluated at the cycle level with slow terminal clearance (STC) defined as > 72 h to clear from < 0.2 µmol/L to < 0.05 µmol/L.ResultsOverall, 135 patients were included with a total of 462 cycles, median of 3 cycles, and 76 (56.3%) experienced at least one cycle of STC. Of 462 cycles, 138 (29.9%) were STC. Multivariable analysis, based on variables significant by univariable analysis, identified that age ≥ 80 years, BMI > 30 kg/m², first MTX level > 10.0 µmol/L, and acute kidney injury (AKI) after MTX administration were significantly associated with STC.ConclusionUtilizing clinically and statistically significant variables from our analyses, we advocate for the development and validation of a model to inform supportive care management once MTX levels decline below 0.2 µmol/L.