Multicenter retrospective analysis of 118 cases of Primary Central Nervous System Diffuse Large B-Cell Lymphoma

Abstract Purpose To retrospectively evaluate the efficacy of high-dose methotrexate (HD-MTX)-based regimens in patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) and to assess the impact of consolidation with hematopoietic stem cell transplantation (HSCT) or maintenance therapy on long-term survival. Methods A total of 118 patients with PCNS-DLBCL treated between January 2016 and December 2023 were enrolled and assigned to five groups based on treatments: radiotherapy alone (n = 24), HD-MTX monotherapy (n = 17), HD-MTX plus temozolomide (n = 18), rituximab combined with HD-MTX and temozolomide or radiotherapy (n = 39), and rituximab–HD-MTX–temozolomide plus a Bruton’s tyrosine kinase(BTK) inhibitor (n = 20). Results The median follow-up was 57 months. The four-drug group showed significantly longer overall survival (OS) and progression-free survival (PFS) than the other four groups (P = 0.0003 and P = 0.013, respectively). The objective response rate (ORR) after two cycles was also highest in the four-drug group (P = 0.016). Patients receiving BTK inhibitor-containing regimens had a better OS benefit (P = 0.008) and a trend toward improved PFS (P = 0.08). Post-induction strategies included HSCT consolidation (n = 16), maintenance therapy (n = 32), and observation (n = 70). Both HSCT and maintenance therapy were associated with prolonged OS compared with observation (P = 0.013 and P = 0.016, respectively); maintenance therapy also improved PFS (P = 0.033). Conclusion The four-drug regimen containing a BTK inhibitor demonstrated favorable efficacy and a high ORR after two cycles in PCNS-DLBCL. Post-induction HSCT or maintenance therapy may further improve survival outcomes. BTK inhibitor-containing regimens showed a promising trend toward long-term survival benefit, warranting further investigation.