De novo secondary central nervous system lymphoma: A real-world cohort study over two decades

Abstract Secondary central nervous system lymphoma (SCNSL) involves CNS spread of systemic lymphoma, occurring at diagnosis (de novo) or at relapse. While SCNSL is associated with more aggressive disease and poorer prognosis, de novo presentation often has more favourable outcomes than relapsed disease. However, there is a lack of real-world data to guide a more nuanced approach in choosing systemic disease- and CNS-targeting treatment, much less in Asian populations and across various lymphoma subtypes. We reviewed data collected over 25 years (1998 - 2024) from a tertiary cancer institute in Singapore. Out of 2511 recruited patients with B-cell lymphoma and 450 patients with T- and NK/T-cell lymphoma, 2.47% (n=62) and 0.89% (n=4) had SCNSL respectively. Of these 66 patients with SCNSL, predominant lymphoma histologies included diffuse large B-cell lymphoma (DLBCL) 62% (n=41), Burkitt lymphoma 12% (n=8), peripheral T-cell lymphoma (PTCL) 6% (n=4) and lymphomatous granulomatosis 4% (n=3). With regards to systemic treatment, 75.8% (n=50) of patients received CHOP-based regimens and 15% (n=10) Hyper-CVAD. CNS-targeting treatment included intrathecal methotrexate (IT MTX) 31.8% (n=21), intravenous methotrexate (IV MTX) 25.8% (n=17) combination IT MTX and IT cytarabine (ARA-C) 18.2% (n=12), and both IV and IT MTX 13.6% (n=9). 10.6% of patients (n=7) received no CNS-directed therapy. At median follow-up of 7.1 years, median overall survival (OS) was 22.4 years with 15 deaths (23%). Median progression-free survival (PFS) was not reached. Five-year and 10-year OS rates were identical at 75.4% (95% CI: 61.9 to 84.7%); 5-year PFS was 58.4% (95% CI: 44.4 to 70.1) and 10-year PFS was 52.1% (95% CI: 37.0 to 65.2%). Comparing patients receiving CNS-targeting treatment and those without, there was no significant difference in OS (p=0.659) and PFS (p=0.890). There was also no statistically significant difference in OS (p=0.949) and PFS (p=0.490) among patients receiving different CNS-targeting treatments. This is the largest retrospective cohort study of de novo SCNSL patients in Asia. De novo SCNSL demonstrated favourable outcomes with median OS of more than 20 years. Further studies on optimal CNS-targeting regimens are warranted.