Central nervous system prophylaxis in aggressive B-cell non-Hodgkin lymphomas 公开

Abstract

Relapses involving the central nervous system (CNS) are uncommon among patients with diffuse large B cell lymphoma (DLBCL) but carry very poor prognosis. Prophylaxis is heterogeneously prescribed around the time of frontline therapy to prevent this outcome, with no clear standard of care in terms of recipient selection or route of administration. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline chemoimmunotherapy between 2013-2019.

Prophylaxis was administered intrathecally (IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). 

Sixty-four patients (5.7 %) had CNS relapse, after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4 vs 6.8%, p=0.4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected versus observed CNS relapse rates were nearly identical (5.8 vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors.

This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated and reconsideration of prophylaxis strategies in DLBCL is of critical need. Development of follow-up studies and anticipated future directions for the prevention and management of CNS relapse are described.

Table of Contents

I.                   Preface …………………………………………………………………………………..….…. 1

II.                 Introduction…………………………………………………………………………………..... 3

III.              Methods …………………………………………………………………………………..…… 5

IV.              Results ……………………………………...………………………………………………..... 7

V.                Discussion …………………………………………………………………………………….. 12

VI.              Subsequent studies………………………………………………………………………...…... 16

VII.           Conclusions……………………………………………………………………………………..19

VIII.         Tables and Figures ………………………………………………………………………….… 20

References …………………………………………………………………………………..… 26

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery
关键词	lymphoma prophylaxis central nervous system non-hodgkin
Committee Chair / Thesis Advisor	Matthew Magee, Emory University
Committee Members	Kristie Blum, Emory University Jonathon Cohen, Emory University

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