Central nervous system relapse of diffuse large B-cell lymphoma in the rituximab era: Results of the UK NCRI R-CHOP-14 versus 21 trial

M. Gleeson, N. Counsell, David Cunningham*, N. Chadwick, A. Lawrie, E. A. Hawkes, A. McMillan, K. M. Ardeshna, A. Jack, P. Smith, P. Mouncey, C. Pocock, J. A. Radford, J. Davies, D. Turner, A. Kruger, P. Johnson, J. Gambell, D. Linch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial. Patients and methods: The R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥ 18 years with bulky stage I-IV DLBCL (n=1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated. Results: 177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX) n=163, intravenous (IV) MTX n=2, prophylaxis type unknown n=11 and IT MTX and cytarabine n=1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolated n=11, with systemic relapse n=10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI,>1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively. Conclusion: Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence.

Original languageEnglish
Pages (from-to)2511-2516
Number of pages6
JournalAnnals of Oncology
Volume28
Issue number10
DOIs
Publication statusPublished - 16 Jul 2017

Keywords

  • Central nervous system
  • Diffuse large B-cell lymphoma
  • Relapse
  • Rituximab

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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