(129) Impact of a Pharmacist-Driven Protocol for High-Dose Methotrexate Monitoring and Leucovorin Rescue

Poster Abstract: Background
Treatment with high-dose methotrexate (HDMTX) at doses ≥500 mg/m2 with leucovorin rescue is part of the standard of care for many malignancies, including primary central nervous system lymphoma (PCNSL), secondary CNS lymphomas, acute lymphoblastic leukemia (ALL), and osteosarcoma. Although HDMTX provides increased clinical efficacy in these disease states, it has many known toxicities including nephrotoxicity from acute kidney injury (AKI), hepatotoxicity, myelosuppression, and mucositis. This prolongs drug exposure and can lead to significant morbidity and mortality without prompt recognition and management. In addition to increased toxicity, grade ≥3 AKI has been shown to significantly prolong hospital length of stay (LOS) and lead to subsequent reduction of chemotherapy dose intensity. Because of these known toxicities and outcomes, many institutions have implemented guidelines for management of HDMTX. In 2021, UCM introduced a pharmacist-driven protocol for HDMTX. This study aims to assess the impact of the protocol implementation by comparing pre-implementation and post-implementation phases, focusing on safety and potential cost savings associated with the HDMTX regimen.
Objectives
The primary objectives of this analysis were to evaluate protocol compliance for ordering of methotrexate levels and leucovorin adjustments per dosing nomogram. Secondary objectives include incidence of drug-drug interactions and time from HDMTX clearance to supportive care discontinuation. Safety endpoints include incidence of AKI (defined as SCr ≥0.3 mg/dL within 48h or increase in SCr ≥ 1.5 times baseline), and liver toxicity (indicated by increased transaminases (AST/ALT) or total bilirubin greater than 2 times the upper limit of normal). Additionally, the study will assess the total duration of leucovorin rescue therapy and sodium bicarbonate infusion.
Methods
This study is a single centered retrospective chart review. All patients treated with HDMTX had a “Consult to Pharmacist HDMTX Monitoring” order embedded within the order set. Upon review of methotrexate levels, pharmacists adjusted leucovorin dosing and frequency using a validated, pharmacokinetics-guided nomogram. Pharmacists were responsible for documenting review of methotrexate levels, leucovorin dose adjustments, and drug interaction management, deviations from dosing nomogram and fluid rate management recommendations within the electronic medical record. Daily "i-Vent" entries and "Pharmacist Notes" at different times, including first consult, methotrexate level follow-up, and clearance, provide a full HDMTX management record. Categorical variables are analyzed via Fisher’s exact test or Pearson’s chi-square test. Nonparametric continuous variable are analyzed via Mann-Whitney U test.

Results: pending
Discussion/conclusion: pending

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