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.

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

doi:10.1093/annonc/mdx353

Title

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.

Publication Date

2017-10-01

Author(s)

Gleeson, M

Counsell, Nicholas

Cunningham, D

Chadwick, N

Lawrie, A

Hawkes, Eliza A

McMillan, A

Ardeshna, K M

Jack, A

Smith, P

Mouncey, P

Pocock, C

Radford, J A

Davies, J

Turner, D

Kruger, A

Johnson, P

Gambell, J

Linch, D

Subject

central nervous system

diffuse large B-cell lymphoma

relapse

rituximab

Type of document

Journal Article

OrcId

#PLACEHOLDER_PARENT_METADATA_VALUE#

DOI

10.1093/annonc/mdx353

Abstract

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. 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. 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. 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. ISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.

Link

link

Citation

Annals of Oncology: Official Journal of the European Society for Medical Oncology 2017; 28(10): 2511-2516

Jornal Title

Annals of Oncology: Official Journal of the European Society for Medical Oncology

Austin Health

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