Abstract
Secondary central nervous system (CNS) lymphoma (SCNSL) in mantle cell lymphoma (MCL) is associated with dismal outcomes, and risk factors are not well documented. This population-based study reports the incidence of SCNSL, risk factors and survival. All patients diagnosed with MCL in Denmark in 2010-2022 without confirmed CNS involvement at diagnosis were included. Data were retrieved from the Danish National Lymphoma Registry and medical records. In total, 873 patients (median age 70 years) were included. The 10-year cumulative incidence of SCNSL was 3.8% (95% confidence interval [CI] 2.4-5.2). Risk factors for SCNSL were blastoid/pleomorphic MCL (hazard ratio [HR] 3.55, 95% CI 2.05-6.14), Ki67 ≥30% (HR 5.47, 95% CI 1.86-16.10) and elevated lactatedehydrogenase (HR 4.35, 95% CI 1.91-9.91). The 5-year cumulative incidence of SCNSL for patients with blastoid/pleomorphic MCL was 9.9% (95% CI 4.0-15.7). Patients with high CNS international prognostic index (CNS-IPI) had a high 1-year incidence of SCNSL of 5.8% (95% CI 1.6-10.0). Median progression-free survival and overall survival were 1.8 months (95% CI 1.3-4.7) and 2.4 months (95% CI 1.3-8.9). In conclusion, SCNSL of MCL is rare and associated with poor survival. Blastoid/pleomorphic subtype and high CNS-IPI identified patients at high risk of SCNSL for whom upfront screening for CNS involvement should be considered.