Relapse of the central nervous system of lymphoma is not affected by the method of prophylaxis


Results from a study of patients with certain aggressive B-cell non-Hodgkin’s lymphomas (NHLs) indicated that central nervous system (CNS) relapse in these patients was not dependent on the route of CNS prophylaxis. However, disease-related factors seemed to impact the risk of CNS relapse. The results of the study were reported in the journal Blood.

The study was a multicenter retrospective analysis involving 1162 patients with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), or transformation to DLBCL or HGBL from certain indolent B-cell NHLs . Patients received CNS prophylaxis with first-line therapy between 2013 and 2019, and this was administered either intrathecally (IC) or as systemic high-dose methotrexate (HD-MTX). Patients were categorized for risk of CNS relapse according to International Prognostic Index (IPI) scores using the CNS-IPI and National Comprehensive Cancer Network-IPI scales. The primary endpoint was CNS relapse. Progression-free survival (PFS) and overall survival (OS) were also assessed.

Of 1130 patients included in the efficacy analysis, 894 received IT prophylaxis and 236 received systemic HD-MTX prophylaxis. A further 32 patients were excluded from the efficacy analysis due to a change in route of administration due to toxicity. The overall median age of patients was 62 years (range: 18-86) and 67% of patients had DLBCL. The CNS-IPI classification indicated that 18% of patients had low-risk status, 51% had moderate-risk status, 30% had high-risk status, and 5.9% had incomplete data for this assessment.

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CNS relapse occurred in 64 patients (5.7%) and of these, 15 (23%) experienced it within the first 6 months after diagnosis. Overall, the median time to CNS relapse occurred at 7.8 months. CNS relapses were observed at similar rates regardless of route of administration of CNS prophylaxis, occurring in 5.4% of patients on IT prophylaxis and 6.8% of patients on HD-MTX (P =.4). Similarities in CNS relapse rates were also observed after performing propensity score matching analysis.

In an analysis of relapse rates based on the weighting of CNS-IPI scores, the expected relapse rate was 5.8%, compared to the observed rate of 5.7%. However, patients with testicular involvement often had lower CNS-IPI scores, but they had a relatively high rate of CNS relapse, occurring in 12% of patients overall and 11% in those with lower CNS-IPI scores. were low to moderate. Non-germline center DLBCL subtype and high extranodal load have also been reported to be associated with increased CNS risk. Double impact lymphoma does not appear to be a predictor of CNS relapse.

At a median follow-up of 2.4 years, median PFS had not been achieved, with a 2-year PFS rate of 71%. The median OS had also not been reached by this follow-up, with a 2-year OS rate of 82%. Prophylaxis-related toxicities were reported in 12% of the total patient population, with a higher rate (25.4%) in patients receiving HD-MTX than with IT prophylaxis (6%; P <.0001>

“This real-world analysis found no difference between IT and HD-MTX in preventing CNS relapses in DLBCL,” the study investigators concluded in their report.

Disclosures: Some authors have disclosed affiliations or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Orellana-Noia VM, Reed DR, McCook AA, et al. Single-route CNS prophylaxis for aggressive non-Hodgkin’s lymphoma: actual results from 21 US academic institutions. Blood. 2022;139(3):413-423. doi:10.1182/blood.2021012888


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