Response‐adapted consolidation and salvage strategies in secondary central nervous system lymphoma: Insights from a multicentre cohort

Secondary central nervous system lymphoma (SCNSL) remains a rare but challenging manifestation of aggressive lymphomas, with limited prospective data to guide treatment decisions in the modern therapeutic era. We conducted a multicentre retrospective cohort study of 105 consecutively treated adult patients diagnosed with SCNSL between 2016 and 2024 across four German academic centres, capturing detailed treatment sequencing, response dynamics and outcome data. Median progression-free survival (PFS) was 7.62 months (95% CI 5.34-9.90), and median overall survival (OS) was 16.62 months (95% CI 5.91-27.33). Consolidation with high-dose chemotherapy and autologous haematopoietic stem cell transplantation (HDT-AHSCT) was associated with significantly improved OS and PFS in univariate and multivariate analyses. Achieving complete remission prior to HDT-AHSCT conferred with superior outcomes. In a small subset of patients with relapsed/refractory (rr) SCNSL, CD19-directed chimeric antigen receptor T-cell (CAR T) therapy showed favourable outcomes compared with non-transplant salvage therapy in exploratory univariate analysis (OS HR 0.28, 95% CI 0.08-0.94, p = 0.039; PFS HR 0.37, 95% CI 0.16-0.88, p = 0.025). In this contemporary multicentre real-world cohort, early response and consolidative HDT-AHSCT emerged as key determinants of durable disease control, while CAR T therapy may represent a salvage strategy for selected patients. These findings provide clinically relevant benchmarks to inform risk-adapted treatment sequencing in SCNSL.