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

Megan Fleming; Ying Huang; Emily Dotson; David A Bond; John Reneau; Narendranath Epperla; Lapo Alinari; Jonathan Brammer; Beth Christian; Robert A Baiocchi; Kami Maddocks; Yazeed Sawalha

doi:10.1177/20406207221112900

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

Ther Adv Hematol. 2022 Jul 23:13:20406207221112900. doi: 10.1177/20406207221112900. eCollection 2022.

Affiliations

¹ Department of Pharmacy, The Ohio State University, Columbus, OH, USA.
² Division of Hematology, The Ohio State University, Columbus, OH, USA.
³ Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, The Ohio State University, 1140B Lincoln Tower, 1800 Cannon Dr, Columbus, OH 43210, USA.

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.

Keywords: CNS involvement; DLBCL; RM-CHOP; high-grade B-cell lymphoma; methotrexate.