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

TC El-Galaly, CY Cheah, MD Bendtsen, GS Nowakowski, R Kansara, KJ Savage, JM Connors, LH Sehn, N Goldschmidt, A Shaulov, U Farooq, BK Link, AJM Ferreri, T Calimeri, C Cecchetti, EJ Dann, CA Thompson, T Inbar, MJ Maurer, IL GadeMB Juul, JW Hansen, S Holmberg, TS Larsen, S Cordua, NG Mikhaeel, M Hutchings, JF Seymour, MR Clausen, D Smith, S Opat, M Gilbertson, G Thanarajasingam, D Villa

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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. © 2018 Elsevier Ltd
Original languageEnglish
Pages (from-to)57-68
Number of pages12
JournalEuropean Journal of Cancer
Volume93
Issue number4
DOIs
Publication statusPublished - 2018

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El-Galaly, TC., Cheah, CY., Bendtsen, MD., Nowakowski, GS., Kansara, R., Savage, KJ., Connors, JM., Sehn, LH., Goldschmidt, N., Shaulov, A., Farooq, U., Link, BK., Ferreri, AJM., Calimeri, T., Cecchetti, C., Dann, EJ., Thompson, CA., Inbar, T., Maurer, MJ., ... Villa, D. (2018). Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma. European Journal of Cancer, 93(4), 57-68. https://doi.org/10.1016/j.ejca.2018.01.073