Outcomes of patients with diffuse large B-cell and high-grade B-cell lymphomas with synchronous CNS and systemic involvement at diagnosis treated with high-dose methotrexate and R-CHOP: a single-center retrospective study

Abstract

Background: The optimal treatment of patients with systemic diffuse large B-cell (DLBCL) or high-grade B-cell (HGBL) lymphomas with synchronous central nervous system (CNS) involvement at diagnosis is not well defined. High-dose methotrexate administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited. Objective: To report our experience with RM-CHOP in patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis. Design: A single-center retrospective analysis. Methods: We identified consecutive patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis who were treated with RM-CHOP from January 2012 to January 2021. Results: Fifty patients were included with a median age of 62 years; 82% had DLBCL ( n = 41) and 18% had HGBL ( n = 9). Treatment with RM-CHOP was followed by consolidative autologous hematopoietic cell transplantation in 14 patients (28%). The complete response (CR) rate following RM-CHOP was 62%. With a median follow-up of 40 months, the median progression-free (PFS) and overall (OS) survivals were 16 and 58 months, and the 2-year PFS and OS were 41% and 57%, respectively. The 2-year cumulative incidence of CNS progression/relapse was 29%. Outcomes were particularly poor in HGBL, with median PFS and OS of 6 and 7 months, compared with median PFS and OS of 22 months and not reached in DLBCL, respectively. The outcomes of patients with relapsed/progressive disease were poor, with only 63% of patients receiving subsequent treatments and only 21% achieving CR to next subsequent treatment. Most patients (58%) with disease relapse/progression had CNS involvement which was associated with very poor outcomes (median OS of 2 months). Conclusion: CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis dictates clinical outcomes and requires more effective treatment options.

Diffuse large B‐cell lymphoma at risk of secondary CNS involvement: The inefficacy of intravenous high‐dose methotrexate CNS prophylaxis and the importance of baseline cerebrospinal fluid analysis

“…Disease factors associated with CNS involvement at baseline are not well defined. 2,4,6,10 While focussing on leptomeningeal involvement, we did not observe significant differences in disease characteristics between CNSinv and noCNS patients, in concordance with Wight and colleagues. 2 We corroborated their finding that the vast majority of patients with asymptomatic leptomeningeal involvement at diagnosis had one or more extra-nodal sites of systemic disease.…”

“…Disease factors associated with CNS involvement at baseline are not well defined 2,4,6,10 . While focussing on leptomeningeal involvement, we did not observe significant differences in disease characteristics between CNSinv and noCNS patients, in concordance with Wight and colleagues 2 .…”

“…Screening high‐risk asymptomatic patients for leptomeningeal involvement at diagnosis is extremely important given the propensity for occult cases to present with early CNS relapse with high mortality risk 1 . There is no standard of care therapy for such patients 2–10 …”