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
2017-10Author
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
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Show full item recordAbstract
<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.
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Licenseref URL
https://creativecommons.org/licenses/by-nc/4.0Funder
The Institute of Cancer Research (Grant ID: Unspecified)
Version of record
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