Cumulative pre-chemoimmunotherapy dexamethasone dose is associated with adverse outcomes in primary central nervous...

Dexamethasone is administered postoperatively and concomitantly with induction regimens and consolidation therapy in patients with primary central nervous system lymphoma (PCNSL). This study aimed to evaluate the impact of cumulative dexamethasone administration prior to systemic chemoimmunotherapy on overall survival (OS) and progression-free survival (PFS) in patients with PCNSL.

We conducted a multicenter retrospective study of 105 patients with newly diagnosed, histologically confirmed PCNSL who underwent chemoimmunotherapy between 2014 and 2024. Patients were dichotomized according to cumulative dexamethasone exposure prior to chemoimmunotherapy using an exploratory threshold of 154 mg determined by the maximally selected log-rank statistic.

High cumulative dexamethasone exposure group (HDE, >154 mg) was associated with significantly worse OS (p <.001) and PFS (p <.001) compared with the low cumulative dexamethasone exposure group. In univariate analysis, HDE was significantly associated with poor outcome and increased mortality (p = .0001), whereas other clinical variables such as Karnofsky Performance Status (p = .800), ASA score (p = .052), and tumor volume (p = .778) did not show significant associations. In multivariate Cox regression, cumulative dexamethasone exposure remained independently associated with poorer survival (p = .002), while autologous stem cell transplantation was associated with improved survival (p = .002).

HDE prior to chemoimmunotherapy was independently associated with worse survival outcomes in patients with PCNSL. A cumulative dexamethasone dose of 154 mg was identified as an exploratory threshold associated with survival differences and requires prospective validation before clinical implementation.