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

Abstract

BackgroundCentral 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 methodsThe 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.Results177/984 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.ConclusionDespite 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.ClinicalTrials.govISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.

Primary breast diffuse large B‐cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure

“…with an estimated 10-year cumulative risk of 28.3%, which is comparable to that of primary testicular DLBCL. 28,29 Notably, in contrast to the general observation that CNS relapse in DLBCL occurred early (median, 6.7-8.1 months), [30][31][32][33] the PB-DLBCL patients in our study showed a persistent risk of CNS relapse occurring up to 8.2 years after initial diagnosis (median, 3.1 years). In addition, our study showed for the first time that synchronous bilateral breast involvement was significantly associated with a higher risk of early CNS progression compared with patients with unilateral breast disease.…”

“…Multivariate analyses of predictive factors for progression-free survival (PFS) and overall survival (OS) in Chinese patients with primary breast diffuse large B-cell lymphoma without IT prophylaxis. This finding is in line with several other studies of DLBCL that suggested the inadequate efficacy of intrathecal prophylactic chemotherapy in preventing CNS disease 30,32,33. As brain parenchymal relapse was more common than leptomeningeal relapse in PB-DLBCL, a more promising option would be systemic CNS chemotherapy prophylaxis such as high-dose i.v.…”

Selective contrast‐enhanced computed tomography is appropriate in diffuse large B‐cell lymphoma therapy response assessment

“…Half of these patients (2% of all analyzed patients) showed new central nervous system involvement, which is in line with previously reported data (2%-8%). 22,23 Overall, the involvement of initially not affected sites at relapse in the current analysis indicates the necessity of a full imaging at relapse. should be considered as an imaging modality in future studies.…”

Impact of Central Nervous System International Prognostic Index on the treatment of Diffuse Large B Cell Lymphoma

“…In 5 of the DHSNHL trials, prophylaxis was mandated for patients with bone marrow, testicular or head and neck lymph nodesinvolvement [13] while in the United Kingdom National Cancer Research Institute [UK NCRI]trial, prophylaxis was given to patients with bone marrow, peripheralblood, nasal/paranasal sinuses, orbit and testicular involvement [6].…”

“…Using the standard combination chemo-immunotherapy RCHOP regimen [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone], 70% of cases are expected to be cured, while 30% will have refractory or relapsed disease [3.4]. Although relapse in the central nervous system [CNS] is relatively rare, occurring in about [2-4%] [5,6],it is a devastating event with a median survivalof usually less than 6 months [7.8].…”