Induction intensity in transplant-eligible primary CNS lymphoma: no survival benefit despite increased toxicity

Primary central nervous system lymphoma is an aggressive lymphoma for which high-dose chemotherapy followed by autologous stem cell transplantation is standard first-line treatment in eligible patients; however, the optimal induction regimen remains uncertain. We conducted a multicenter international retrospective study across 11 centers including 355 transplant-eligible patients treated with MATRix (n=164), R-MPV/R-MT (n=121), or the reduced-intensity Alberta protocol (n=70). The overall response rate was 89.5%, with a complete response rate of 50.1%. Although complete response rates were higher with R-MPV/R-MT, transplantation rates were similar across regimens (74.4%, 69.4%, and 78.6%, respectively; p=0.36). Two-year overall survival was 79.0%, 89.0%, and 82.1% (p=0.32), and 2-year progression-free survival was 63.7%, 72.6%, and 75.3% (p=0.26) for MATRix, R-MPV/R-MT, and Alberta, respectively. Comparable outcomes were also observed among patients proceeding to transplantation (n=261). Toxicity however differed substantially between regimens: MATRix was associated with higher rates of dose reductions (p=0.006), ICU admissions (p<0.001), and treatment-related mortality (p=0.006). After adjustment for baseline imbalances using inverse probability of treatment weighting, survival outcomes remained comparable across treatment groups, whereas MATRix retained a less favorable toxicity profile. Less intensive induction regimens achieved transplantation and survival outcomes comparable to MATRix while demonstrating superior tolerability, supporting treatment strategies that optimize tolerability without compromising long-term outcomes.