Results from a study involving patients with certain aggressive B-cell non-Hodgkin lymphomas (NHLs) indicated that central nervous system (CNS) relapse in these patients did not depend on route of CNS prophylaxis. However, disease-related factors did appear to impact CNS relapse risk. The study results 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 were given CNS prophylaxis with frontline therapy in the time period between 2013 and 2019, and this was administered either intrathecally (IC) or as systemic high-dose methotrexate (HD-MTX). Patients were classified for CNS relapse risk according to International Prognostic Index (IPI) scores using 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 evaluated.

Among 1130 patients included in efficacy analysis, 894 received IT prophylaxis, and 236 received systemic HD-MTX prophylaxis. Another 32 patients were excluded from efficacy analysis due to switching between routes of administration because of toxicity. The overall median patient age was 62 years (range, 18-86), and 67% of patients had DLBCL. 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 (5.7%) patients, and of these, 15 (23%) experienced this within the initial 6 months after diagnosis. Overall, the median time to CNS relapse occurred at 7.8 months. CNS relapse was seen at similar rates regardless of the route of CNS prophylaxis administration, occurring in 5.4% of patients with IT prophylaxis and 6.8% of patients with HD-MTX (P =.4). Similarities in CNS relapse rates were also seen after a propensity score-matching analysis was performed.

In an analysis of relapse rates based on weighting of CNS-IPI scores, the expected relapse rate was 5.8%, compared with the observed rate of 5.7%. However, patients with testicular involvement often showed lower CNS-IPI scores, but they showed a relatively high rate of CNS relapse, occurring in 12% overall and 11% among those with low to moderate CNS-IPI scores. Nongerminal center DLBCL subtype and high extranodal burden were also reportedly associated with greater CNS risk. Double-hit lymphoma did not appear to be a predictive factor for CNS relapse.

At a median follow-up of 2.4 years, the median PFS had not been reached, 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 relapse in DLBCL,” the study investigators concluded in their report.

Disclosures: Some authors have declared affiliations with or received grant support 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 lymphomas: real-world outcomes from 21 US academic institutions. Blood. 2022;139(3):413-423. doi:10.1182/blood.2021012888