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Ferrata Storti Foundation
Haematologica 2020 Volume 105(7):1914-1924
Non-Hodgkin Lymphoma
Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in
the rituximab era: a systematic review
Toby A. Eyre,1 Faouzi Djebbari,2 Amy A. Kirkwood3 and Graham P. Collins1
1Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford; 2Department of Pharmacy, Oxford University Hospitals NHS Foundation Trust, Oxford and 3Cancer Research UK & UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
ABSTRACT
Central nervous system (CNS) relapse of diffuse large B-cell lym- phoma remains uncommon but catastrophic. The benefit of stand- alone intrathecal prophylaxis in reducing CNS recurrence is unclear and remains controversial. No systematic review analysing the evidence for stand-alone intrathecal prophylaxis has been performed in the era of anti- CD20 monoclonal antibody therapy. A comprehensive search (01/2002- 01/2019) was systematically performed using Ovid MEDLINE®, Ovid EMBASE® and Cochrane. Studies were selected from a total of 804, screened based on predefined inclusion/exclusion criteria, and were critical- ly appraised. Three post hoc analyses (RICOVER-60, RCHOP-14/21, GOYA), one prospective database and 10 retrospective series were includ- ed. 7,357 rituximab/obinutuzumab-exposed patients were analysed. The median percentage receiving intrathecal prophylaxis was 11.9%. Cumulative CNS relapse incidence ranged from 1.9% at 6.5 years to 8.4% at 5 years. Median time (of medians) to CNS relapse was 10 months. 73% developed isolated CNS relapses, 24% concurrent CNS/systemic relapse, and 3% post-systemic relapse. Reported CNS relapse sites were: parenchy- mal (58%), leptomeningeal (27%), and both (12%). Event rates were low resulting in limited power within each study to provide robust univari- able/multivariable analysis. Intrathecal prophylaxis was not a univariable or multivariable factor associated with a reduction in CNS relapse in any study. We found no strong evidence for the benefit, or indeed genuine lack of benefit, of stand-alone intrathecal prophylaxis in preventing CNS relapse in diffuse large B-cell lymphoma-treated patients using anthracycline-based immunochemotherapy. Current published study designs limit the strength of such conclusions.
Introduction
Relapse of diffuse large B-cell lymphoma (DLBCL) within the central nervous system (CNS) following front line anthracycline-based immunochemotherapy is relatively uncommon (typically 2-5%).1–4 It typically occurs within the first year of follow up post-treatment and has devastating consequences. The median overall survival following recurrence within the CNS is approximately 2-5 months5,6 with few patients achieving long term survival. As a result, attempts over many years have been made to reduce the risk of this complication of DLBCL. Although risk factors1,4 for CNS relapse have been clearly described over recent years and the CNS international prognostic index (CNS-IPI) has been established and validated, the optimal and widely applicable CNS prophylactic strategy remains somewhat con- troversial.
High dose, systemic anti-metabolite therapy, typically in the form of high dose methotrexate (HDMTX), is the most commonly employed systemic prophylactic
Correspondence:
TOBY A. EYRE
toby.eyre@ouh.nhs.uk
Received: June 20, 2019. Accepted: September 2, 2019. Pre-published: September 5, 2019.
doi:10.3324/haematol.2019.229948
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/7/1914
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