Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

Abstract

Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited.

Methods: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records.

Results: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9).

Conclusions: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.

Keywords: Autologous stem cell transplant; Central nervous system; Diffuse large B-Cell lymphoma; Rituximab; Secondary CNS.

Figure 1

A–C: Overall survival (OS) in SCNS patients according to the presence systemic involvement at the time of SCNS (1A, 17 patients excluded due to missing information on disease status outside CNS disease) and according to treatment protocol (Intensive vs. palliative vs. best supportive care, 1B) or achieving complete remission after first-line SCNS therapy (1C, n=67 including 20 patients undergoing HDT with ASCT)

Figure 2

A-D: Survival of patients with SCNS patients treated on intensive protocols according to age (60≤ years vs. >60 years, 2A), ECOG performance score (0–1 vs. 2–4, 2B), site of SCNS (parenchymal, leptomeningeal, both sites, 2C), and during/after first line treatment of SCNS, 2D)

Figure 3

A-D: Impact of treatment selections on OS in SCNS patients without systemic involvement by DLBCL. Survival according to HDMTX treatment regimen (single agent HDMTX vs. combination therapies, 3A), single modality WBRT according to leptomeningeal involvement or not (3B), ASCT versus no ASCT in patients achieving at CR after induction treatment (3C) and outcome according to rituximab use in frontline against isolated SCNS treated with HDMTX-based regimens (3D).