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Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate

Supportive Care in Cancer volume 29, pages 5293–5301 (2021)Cite this article

Abstract

Background

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).

Methods

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.

Results

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).

Conclusion

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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The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Funding

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.).

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Authors and Affiliations

  1. Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Jason N. Barreto

  2. Department of Pharmacy, Duke University Medical Center, 2301 Erwin Road, Durham, NC, 27710, USA

    Kristen T. Peterson

  3. Department of Pharmacy, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Erin F. Barreto

  4. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Kristin C. Mara & Ross A. Dierkhising

  5. Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Nelson Leung

  6. Division of Hematology, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Thomas E. Witzig & Carrie A. Thompson

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Contributions

Conceptualization and methodology: JNB, KTP, EFB, KCM, RAD, NL, TEW, and CAT.

Data curation, formal analysis, and interpretation: JNB, KTP, EFB, KCM, and RAD.

Writing—original draft: JNB, KTP, EFB, KCM, RAD, NL, TEW, and CAT

Writing—review and editing: JNB, KTP, EFB, KCM, RAD, NL, TEW, and CAT

Corresponding author

Correspondence to Jason N. Barreto.

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Ethics approval

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.

Consent to participate

All patients provided written informed consent or had consent provided for them by their legal power of attorney and were verified through Minnesota Research Authorization prior to data collection.

Competing interests

E.F.B. provides consultation for FAST Biomedical, unrelated to this work. All other authors declare no potential personal, financial, or ethical conflicts of interest regarding the contents of this manuscript.

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Abstract information

The material found in this work was presented as a poster at the 61st Annual Meeting and Exposition, December 7-10, 2019, in Orlando, FL.

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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

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Keywords

  • Methotrexate
  • Leucovorin rescue
  • Nephrotoxicity
  • Therapeutic drug monitoring
  • Lymphoma