Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery

Wilson, M. R. et al. (2020) Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery. Blood Advances, 4(15), pp. 3586-3593. (doi: 10.1182/bloodadvances.2020002421) (PMID:32761231) (PMCID:PMC7422120)

Abstract

High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P < .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P < .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post–R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wilson, Dr Matthew and McKay, Dr Pamela
• Authors: Wilson, M. R., Eyre, T. A., Martinez-Calle, N., Ahearne, M., Parsons, K. E., Preston, G., Khwaja, J., Schofield, J., Elliot, J., Mula Kh, A., Shah, N., Cheung, C.-K., Timmins, M. A., Creasey, T., Linton, K., Smith, J., Fox, C. P., Miall, F., Cwynarski, K., and McKay, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Blood Advances
• Publisher: American Society of Hematology
• ISSN: 2473-9529
• ISSN (Online): 2473-9529
• Published Online: 06 August 2020
• Copyright Holders: Copyright © 2020 The American Society of Hematology
• First Published: First published in Blood Advances 4(15): 3586-3593
• Publisher Policy: Reproduced in accordance with the publisher copyright policy