(004) A Retrospective Study Evaluating High-Dose Methotrexate Clearance, with a Focus on Characteristics Associated with Faster Clearance

Poster Abstract:

Background: Methotrexate (MTX) is an antimetabolite chemotherapeutic agent utilized in various regimens for the treatment of lymphomas. In high doses, ≥ 1 g/m2, administration requires inpatient admission and adjunctive supportive care until MTX clears from the serum, which is often considered a serum MTX concentration of < 0.05 micromole/L. Published literature, limited to retrospective studies, have demonstrated that hypoalbuminemia is associated with delayed MTX clearance. Acute kidney injury may also delay clearance, which has been associated with other characteristics such as age and baseline renal function. Data assessing characteristics associated with more rapid MTX clearance are lacking.

Objectives: The primary endpoint was to determine patient characteristics associated with faster methotrexate clearance in the next 72 hours once a patient’s methotrexate level declines below 0.2 micromole/L. Secondary outcomes include the development of a mathematical model with criteria for “fast clearers” and “slow clearers”; evaluate the accuracy of MTXPK.org prediction of MTX clearance at 72 hours once a patient’s MTX level declines below 0.2 micromole/L; and to estimate the potential impact of a MTX clearance predictive model for “fast clearers” on hospital length of stay.


Methods: We performed a single-center, retrospective cohort study to evaluate patient-specific factors associated with the rate of MTX clearance in the 72 hours after serum MTX levels decline below 0.2 micromol/L. Clinical data were collected for adults patients who received high-dose methotrexate at doses ≥ 3 g/m2 for the treatment of lymphoma at The James Comprehensive Cancer Center at The Ohio State University from January 1, 2015 to October 1, 2023. MTX administrations were evaluated at the cycle level and each unique administration was independently evaluable and stratified by the outcome of “fast clearance”, defined as ≤ 72 hours to clear from < 0.2 micromole/L to < 0.05 micromole/L, or “slow clearance”, defined as > 72 hours to clear from < 0.2 micromole/L to < 0.05 micromole/L. Characteristics were assessed via univariate analysis to determine which variables were most likely associated with high-dose MTX clearance, then analyzed using multivariate analysis to evaluate association with clearance.

Results/

Conclusions: Data collection and analysis are ongoing and will be presented at the 2024 HOPA Annual Conference.

References (must also be included in final poster): 1. National Comprehensive Cancer Network. B-Cell Lymphomas (Version 5.2023). Accessed September 23, 2023.
2. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist. 2016;21(12):1471-1482. doi:10.1634/theoncologist.2015-0164
3. Relling MV, Fairclough D, Ayers D, et al. Patient characteristics associated with high-risk methotrexate concentrations and toxicity. J Clin Oncol. 1994; 12:1667-1672.
4. Leila Mohassel, Sarah Griffin, Nicole Binder, Scott D. Barnett, Raymund Cuevo; Evaluation of Methotrexate Clearance in Adult and Pediatric Patients with Hypoalbuminemia. Blood 2019; 134 (Supplement_1): 2906.
5. Reiss SN, Buie LW, Adel N, Goldman DA, Devlin SM, Douer D. Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia. Ann Hematol. 2016;95(12):2009-2015.
6. Amitai, I, Rozovski, U, El-Saleh, R, et al. Risk factors for high-dose methotrexate associated acute kidney injury in patients with hematological malignancies. Hematological Oncology. 2020; 38: 584–588.
7. Wiczer T, Dotson E, Tuten A, Phillips G, Maddocks K. Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity. J Oncol Pharm Pract. 2016; 22(3):430-436.