The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Prophylaxis against central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) with high-dose methotrexate (HD-MTX) may be most beneficial when administered as early as possible or following during R-CHOP, according to a retrospective analysis presented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.

Although CNS relapse of DLBCL is rare, it is associated with poor outcomes. However, some data suggest that HD-MTX may decrease the risk of CNS relapse. Because CNS relapse takes a median of 6 to 8 months to develop, “there is rationale to deliver prophylactic, CNS-directed therapy as early as possible to high-risk patients,” Matthew Wilson, MD, BSc, MRCP, of the Beatson West of Scotland Cancer Centre in the United Kingdom, and lead author and presenter, said.

This multicenter, retrospective study included 334 patients with DLBCL who received HD-MTX intercalated between R-CHOP cycles (i-HD-MTX) or HD-MTX given at the end of R-CHOP (EOT). Univariate and multivariate analyses were conducted to determine risk factors for delay of R-CHOP cycles.

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The overall baseline characteristics included a median age of 61 years, 59% of patients were male, and 27% had a performance status at least 2. Risk for CNS relapse was considered high among 46% of patients, based on IPI criteria. More patients in the EOT arm had a performance status of 2 or higher, renal/adrenal involvement, were considered high risk for CNS relapse, and had received intrathecal prophylaxis.

A delay in the next R-CHOP cycle occurred in 20% of the 409 i-HD-MTX cycles administered, with a median of 7 days (range, 2-150 days); of these, 14% were attributed to MTX. I-HD-MTX resulted in more R-CHOP delays than EOT at 3 or more days (44% vs 23%; P <.001) or at 7  or more days (32% vs 15%; P =.001). The use of i-HD-MTX was  significantly independently associated with delay in R-CHOP in the multivariate analysis (odds ratio [OR], 3.06; 95% CI, 1.62-5.77).

However, HD-MTX given more than 10 days after R-CHOP also conferred a significant risk for R-CHOP delay (OR, 1.74; 95% CI, 1.03-2.93).

Overall, 5.7% of patients developed a CNS relapse, with a 3-year cumulative incidence of 5.9% (95% CI, 3.0-8.8%). The incidence was similar between the i-HD-MTX and EOT groups.

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Both PFS and OS were similar between groups during the median follow-up of 2.4 years.

Most rates of adverse events (AEs) were similar between groups, except i-HD-MTX resulted in higher rates of mucositis and grade 3 febrile neutropenia. Inpatient stay was longer by a median of 1 day in the i-HD-MTX group compared with the EOT group.

“Our conclusion is, therefore, that either of these approaches can be considered,” Dr Wilson said. “Our data should allow a more detailed assessment of competing risks on an individual patient basis when deciding which prophylaxis approach to take.”

Read more of Cancer Therapy Advisor‘s coverage of the EHA virtual meeting by visiting the conference page.


Wilson M et al. High dose methotrexate CNS prophylaxis in diffuse large b-cell lymphoma (DLBCL): a multicentre analysis of toxicity and impact on R-CHOP delivery. Paper Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S236.