Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
30617197
PubMed Central
PMC6396175
DOI
10.1182/blood-2018-07-862862
PII: S0006-4971(20)42745-4
Knihovny.cz E-zdroje
- MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie genetika patologie MeSH
- dospělí MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza epidemiologie genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- nádory centrálního nervového systému farmakoterapie genetika sekundární MeSH
- následné studie MeSH
- prediktivní hodnota testů MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- protoonkogenní proteiny c-bcl-2 genetika MeSH
- protoonkogenní proteiny c-myc genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- BCL2 protein, human MeSH Prohlížeč
- MYC protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- protoonkogenní proteiny c-bcl-2 MeSH
- protoonkogenní proteiny c-myc MeSH
Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS-International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741.
1st Department of Medicine Charles University General Hospital Prague Czech Republic
AOU Citta' Della Salute e della Scienza SC Ematologia Turin Italy
Bioinformatics Genentech Inc South San Francisco CA; and
Centre for Lymphoid Cancer British Columbia Cancer Agency Vancouver BC Canada
Department of Cellular Biotechnologies and Hematology Sapienza University Rome Italy
Department of Medical Oncology Harbin Medical University Cancer Hospital Harbin China
Department of Oncology Tom Baker Cancer Centre Calgary AB Canada
Oncology Biomarker Development and
Oncology Biomarker Development F Hoffmann La Roche Ltd Basel Switzerland
Pharma Development Biometrics Biostatistics F Hoffmann La Roche Ltd Basel Switzerland
Pharma Development Clinical Oncology F Hoffmann La Roche Ltd Basel Switzerland
SC Ematologia Azienda Sanitaria Universitaria Integrata Trieste Italy
The Ottawa Hospital and Ottawa Hospital Research Institute Ottawa ON Canada
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ClinicalTrials.gov
NCT01287741
