A Retrospective Study of Treatment and Outcomes in Synchronous Systemic and Central Nervous System Large B-cell Lymphoma Open Access

• Synchronous systemic/CNS LBCL is rare yet frontline systemic and CNS-directed chemoimmunotherapy results in durable remission and survival.

• Normal LDH, IPI 2, parenchymal-only CNS involvement, and consolidation with HDC/ASCT were associated with superior clinical outcomes.

Synchronous systemic and de novo secondary central nervous system (CNS) large B-cell lymphoma (LBCL) is an aggressive clinical entity with a historically poor prognosis. Given the rarity of this presentation, prospective studies are limited, and treatment paradigms and outcomes are extrapolated from small heterogenous retrospective studies. We performed a retrospective study with extended follow up for 63 consecutive patients with previously untreated synchronous systemic and de novo secondary CNS LBCLs presenting to two institutions over 21 years. Most patients had diffuse large B-cell lymphoma (73%) and were treated with an average of 6 cycles of R-CHOP intercalated with high dose intravenous methotrexate (R-CHOP-M). The overall response rate was 84% (75% complete). With a median follow up of 8.1 years, the median progression-free survival (PFS) was 1.2 years, and the 6-year PFS rate was 37%. The median overall survival (OS) was 7.9 years and the 6-year OS rate was 52%. Normal lactate dehydrogenase (LDH), low International Prognostic Index (IPI) score, and brain parenchymal-only CNS disease were associated with improved PFS, while LDH and parenchymal disease were associated with OS. The 25% of patients who underwent consolidation with high dose chemotherapy and autologous stem cell transplant (HDC/ASCT) had superior PFS and OS compared to non-transplanted patients, with particular benefit in IPI 3+. This study demonstrates that a proportion of patients presenting with secondary CNS involvement are cured with upfront chemoimmunotherapy with or without HDC/ASCT and helps identify prognostically favorable subgroups which can guide counseling of patients with this rare high-risk clinical presentation.