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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.

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Publication Date
2017-10
ICR Author
Cunningham, David
Marsden,
Author
Gleeson, M
Counsell, N
Cunningham, D
Chadwick, N
Lawrie, A
Hawkes, EA
McMillan, A
Ardeshna, KM
Jack, A
Smith, P
Mouncey, P
Pocock, C
Radford, JA
Davies, J
Turner, D
Kruger, A
Johnson, P
Gambell, J
Linch, D
Type
Journal Article
Metadata
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Abstract
<h4>Background</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Clinicaltrials.gov</h4>ISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.
URL
https://repository.icr.ac.uk/handle/internal/745
Collections
  • Clinical Studies
Licenseref URL
https://creativecommons.org/licenses/by-nc/4.0
Funder
The Institute of Cancer Research (Grant ID: Unspecified)
Version of record
10.1093/annonc/mdx353
Subject
Humans
Central Nervous System Neoplasms
Neoplasm Recurrence, Local
Cyclophosphamide
Vincristine
Doxorubicin
Prednisone
Antineoplastic Combined Chemotherapy Protocols
Drug Administration Schedule
Prospective Studies
Middle Aged
Female
Male
Lymphoma, Large B-Cell, Diffuse
Antibodies, Monoclonal, Murine-Derived
Rituximab
Research team
Medicine (RMH Smith Cunningham)
Language
eng
Date accepted
2017-07-16
License start date
2017-10
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2017, 28 (10), pp. 2511 - 2516

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