Retrospective Analysis of 118 Cases of Primary Central Nervous System Lymphoma

Purpose: To retrospectively analyze the clinical efficacy of high-dose methotrexate (HD-MTX)-based regimens in treating primary central nervous system lymphoma (PCNSL), and to evaluate the impact of autologous hematopoietic stem cell transplantation (AHSCT) or maintenance therapy on long-term survival of patients.

Methods: A total of 118 PCNSL patients treated between January 2016 and December 2023 were included. They were classified into 5 groups based on treatment regimens: single-agent (HD-MTX), two-drug(HD-MTX and temozolomide), three-drug (rituximab, HD-MTX and temozolomide or radiation), four-drug (rituximab, HD-MTX, temozolomide and BTKi), and radiation alone. The number of cases in each group was as follows:17, 18, 39, 20,and 24,respectively. Clinical efficacy and adverse events among these groups were analyzed.

Results: The median follow-up time for the 118 PCNSL patients was 45 months. The median overall survival (OS) was 25 months, and the median progression-free survival (PFS) was 20 months. Subgroup analysis revealed that patients in the four-drug regimen group had significantly higher OS and PFS compared to the other four groups (P values of 0.045 and 0.036, respectively). Additionally, patients in the four-drug group had a significantly higher objective response rate (ORR) after two cycles compared to the other groups (P=0.026). Further analysis demonstrated a trend towards improved OS (P=0.077) and PFS (P=0.067) in the group receiving BTKi-containing regimens. After induction chemotherapy followed by sequential AHSCT or maintenance therapy, the median OS was 25 months and median PFS was 20 months for both the AHSCT group and the maintenance therapy group. Both OS in the maintenance therapy and AHSCT groups were significantly higher than those in the observation group (P values of 0.037 and 0.039, respectively).Similarly, PFS was superior in both the maintenance therapy group and the AHSCT group compared to the observation group (P values were 0.017 and 0.062, respectively). Hematologic toxicity was observed in 53.4% (63/118) of patients, all graded as CTCAE 1-2. Non-hematologic toxicities, mainly nausea, vomiting, and mucositis, were also graded as 1-2 and did not lead to any toxicity-related death.

Conclusion: The use of four-drug regimens based on HD-MTX shows significant efficacy in the treatment of PCNSL, with a higher ORR after two cycles. Post-induction strategies with AHSCT or maintenance therapy further improve treatment efficacy. In addition, regimens containing BTKi indicate a potential benefit in long-term survival, which warrants further investigation.