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Patient selection and tolerability of high-dose methotrexate as central nervous system prophylaxis in diffuse large B-cell lymphoma

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Abstract

Introduction

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is usually fatal. Risk stratification of patients has historically been poorly defined, and CNS prophylaxis with high-dose methotrexate (HDMTX) can be associated with multiple toxicities. The CNS International Prognostic Index (IPI) defines three patient risk groups for CNS disease. The aims of this study were to evaluate the toxicity of HDMTX and describe outcomes in HDMTX and non-HDMTX patients according to the CNS-IPI.

Methods

205 patients diagnosed with DLBCL between 2004 and 2014, initially treated with RCHOP-like chemotherapy and considered for HDMTX CNS prophylaxis were identified by pharmacy records at two teaching hospitals. Patient records were retrospectively reviewed for HDMTX toxicity, CNS-IPI calculation and CNS relapse.

Results

28 patients with DLBCL were selected for two doses of HDMTX. Two of 28 patients received only one dose, and three had their second dose reduced due to renal impairment. 28% of patients experienced nephrotoxicity. 24 HDMTX and 122 non-HDMTX patients were evaluable for the CNS-IPI. No significant difference in the CNS-IPI distribution between the two groups was identified (p = 0.695). Five patients had CNS relapse, two who received HDMTX and three who did not. No significant difference in CNS relapse rate was identified between 24 HDMTX patients propensity-matched to 24 non-HDMTX patients.

Conclusions

HDMTX was well-tolerated by patients. Application of the CNS-IPI identifies a different population of candidates for CNS prophylaxis compared to traditional criteria.

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Abbreviations

DLBCL:

Diffuse large B-cell lymphoma

CNS:

Central nervous system

HDMTX:

Systemic high-dose methotrexate

ITMTX:

Intrathecal methotrexate

IPI:

International Prognostic Index

ECOG:

Eastern Collaborative Oncology Group

LDH:

Lactate dehydrogenase

DSHNHL:

German high-grade non-Hodgkin lymphoma study group

RCHOP:

Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone

CTCAE:

Common terminology criteria for adverse events

ALT:

Alanine aminotransferase

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Acknowledgements

Appreciation and gratitude to the following individuals and institutions who contributed to the completion of this project: Health Information Services and Information Technology staff at Austin and Box Hill hospitals, Austin Clinical School, Olivia Newton John Cancer Wellness and Research Centre, Austin Health and Eastern Health.

Funding

This study did not receive any funding.

Author information

Authors and Affiliations

  1. The University of Melbourne, Parkville, VIC, Australia

    Melissa J. Garwood & Geoffrey Chong

  2. Departments of Haematology and Oncology, Olivia Newton John Cancer, Wellness and Research Centre, Austin Hospital, Heidelberg, VIC, Australia

    Eliza A. Hawkes & Geoffrey Chong

  3. Department of Medical Oncology, Eastern Health, Box Hill, VIC, Australia

    Eliza A. Hawkes

  4. Florey Institute of Neuroscience and Mental Health, Melbourne, Australia

    Leonid Churilov

Authors
  1. Melissa J. Garwood
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  2. Eliza A. Hawkes
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  3. Leonid Churilov
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  4. Geoffrey Chong
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Corresponding author

Correspondence to Geoffrey Chong.

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Conflict of interest

Research funding: Amgen, Beigene, Bristol-Myers Squibb, Pfizer, Merck Serono, Celgene, Merck Sharpe Dome, Novartis, Pharmacyclics, Hutchison MediPharma, Incyte, Bayer. Travel Expenses: Takeda. Advisory board: Janssen.

Ethical approval

Ethical approval was obtained for this non-interventional retrospective study from the institutional research committees.

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Informed consent was not applicable for this non-interventional retrospective study.

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Garwood, M.J., Hawkes, E.A., Churilov, L. et al. Patient selection and tolerability of high-dose methotrexate as central nervous system prophylaxis in diffuse large B-cell lymphoma. Cancer Chemother Pharmacol 85, 133–140 (2020). https://doi.org/10.1007/s00280-019-04007-w

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  • DOI: https://doi.org/10.1007/s00280-019-04007-w

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