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

Lookup NU author(s): Dr Tom Creasey


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© 2020 by The American Society of Hematology.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.

Publication metadata

Author(s): Wilson MR, Eyre TA, Martinez-Calle N, Ahearne M, Parsons KE, Preston G, Khwaja J, Schofield J, Elliot J, Kh AM, Shah N, Cheung C-K, Timmins MA, Creasey T, Linton K, Smith J, Fox CP, Miall F, Cwynarski K, McKay P

Publication type: Article

Publication status: Published

Journal: Blood Advances

Year: 2020

Volume: 4

Issue: 15

Pages: 3586-3593

Print publication date: 11/08/2020

Online publication date: 06/08/2020

Acceptance date: 29/06/2020

ISSN (print): 2473-9529

ISSN (electronic): 2473-9537

Publisher: American Society of Hematology


DOI: 10.1182/bloodadvances.2020002421

PubMed id: 32761231


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