Outcomes of primary CNS lymphoma treated with combined immunochemotherapy with whole-brain radiotherapy.

Purpose: Given that most PCNSL cases are diagnosed at a late age, they may be unsuitable for consolidation therapy with autologous stem cell transplantation (HDC-ASCT). We thus examine the outcomes of PCNSL in a multiethnic Asian population treated with HD-MTX-based chemotherapy and consolidation WBRT, so as to benchmark current treatment outcomes.

Methods: We conducted a retrospective study involving patients (n = 129) diagnosed with PCNSL at the National Cancer Centre Singapore from 2000 to 2019. The median follow-up duration was 47.0 months. Survival analyses were performed using the Kaplan-Meier method and Cox proportional models.

Results: The cohort consisted of 76 male and 53 female patients with a median age of 60 years. 85 patients received HD-MTX-based induction therapy as per DeAngelis, while 44 were treated with the Shah protocol. In univariate analyses, male sex, ECOG scores ≥ 1, non-germinal center subtype, use of DeAngelis protocol, and methotrexate dose < 3 g/m² were significantly correlated with worse PFS and OS. In a multivariate model, the Shah protocol conferred significantly improved outcomes as compared with the DeAngelis protocol for PFS (HR 0.43, 95% CI 0.25-0.73, p = 0.0019) and OS (HR 0.31, 95% CI 0.16-0.59, p = 0.0004). Using gene expression profiling, poor risk PCNSL patients had a higher trend of CD8 T-cells, macrophages and Th-1 cells, upregulation of TIGIT and HAVCR2, and downregulation in WNT11 and CD44.

Conclusion: Our study demonstrates that contemporary HD-MTX-based chemoimmunotherapy induction regimens achieve good disease responses in PCNSL. We also highlight significant prognostic factors and a potential role for immunotherapy in PCNSL.