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Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies.

ABSTRACT: CNS relapse is reported in 2-5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79-95). After a median follow-up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2-32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4-4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4-3.5) compared to patients with non-CNS relapse (6.6 months; 95% CI: 4.6-11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low-intermediate risk according to CNS-IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment-naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.

SUBMITTER: Cabannes-Hamy A

PROVIDER: S-EPMC5852369 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies.

Cabannes-Hamy Aurélie A Peyrade Frederic F Jardin Fabrice F Emile Jean-François JF Delwail Vincent V Mounier Nicolas N Haioun Corinne C Perrot Aurore A Fitoussi Olivier O Lara Diane D Delarue Richard R André Marc M Offner Fritz F Ghesquières Hervé H Pascal Laurent L Soussain Carole C Lazarovici Julien J Schiano Jean-Marc JM Gaulard Philippe P Tilly Hervé H Thieblemont Catherine C

Cancer medicine 20180223 3

CNS relapse is reported in 2-5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituxim ...[more]

PMID: 29473343

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Project description:Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (? 40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.

Project description: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. ClinicalTrials.gov:ISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.

Project description:Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow-up of 53 months (range 5-132 months), 1 progressive disease and 18 relapses occurred. The 5-year time to tumour progression and disease-specific survival were 85% (95% CI 79-91%) and 92% (95% CI 87%-97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease-specific survival between patients treated with abbreviated R-CHOP plus involved field radiotherapy or with 6 to 8 cycles of R-CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.

Dataset Information

Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies.

Publications

Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies.

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