Incidence and Characterization of Secondary CNS Lymphoma in 1,972 Patients with DLBCL - A Danish Nationwide Cohort Study

Secondary CNS involvement (SCNSL) is a rare manifestation of diffuse large B-cell lymphoma (DLBCL) with a poor prognosis. We present updated data from a nationwide study on the incidence and clinical characteristics of SCNSL. The incidence of SCNSL was calculated considering death or relapse without SCNSL as competing risks. Risk factors associated with SCNSL were identified using a cause-specific Cox proportional hazards model. A total of 1972 patients with DLBCL were included and 68 (3.4%) of these experienced SCNSL at first relapse. The crude 1- and 2-year cumulative incidence of SCNSL was 2.0% (95% CI, 1.5-2.7) and 2.6% (95% CI, 2.0-3.4). For patients with a high-risk CNS International Prognostic Index (CNS-IPI) score, the 1- and 2-year cumulative incidence was 6.4% and 7.5%. The number and location of extranodal (EN) sites was the most significant predictor of SCNSL. Specific EN sites associated with increased risk were bone marrow, heart, kidneys/adrenal glands, ovaries, testes and uterus. Median overall survival (OS) after SCNSL was 3.2 months. SCNSL within six months after end of primary treatment (EOT) was associated with a higher baseline CNS-IPI score and worse OS compared to SCNSL more than six months after EOT. Patients with a combination of low-risk CNS-IPI and late-onset SCNSL had the most favorable prognosis. In conclusion, updated real-world population-based data on SCNSL at first relapse, adjusted for competing risks, demonstrated a lower incidence of SCNSL than previously reported, with the number and location of EN sites being the most significant predictors of SCNSL.