In patients exposed to high-dose methotrexate (HDMTX; >1g/m2) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI).
This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 μmol/L) and incident AKI after each HDMTX dose.
The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001).
Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.
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This project was supported in part by CTSA Grant Number TL1 TR002380 from the National Center for Advancing Translational Science (NCATS) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number K23AI143882 (PI - E.F.B.).
This retrospective chart review was approved by the Mayo Clinic Institutional Review Board and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki with adherence to all relevant regulations of the US health insurance portability and accountability act (HIPAA), IRB No. 17-008432, Approved 11 October 2017.
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Barreto, J.N., Peterson, K.T., Barreto, E.F. et al. Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate. Support Care Cancer 29, 5293–5301 (2021). https://doi.org/10.1007/s00520-021-06106-y
- Leucovorin rescue
- Therapeutic drug monitoring