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Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL.

ABSTRACT: 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.

SUBMITTER: Klanova M

PROVIDER: S-EPMC6396175 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL.

Klanova Magdalena M Sehn Laurie H LH Bence-Bruckler Isabelle I Cavallo Federica F Jin Jie J Martelli Maurizio M Stewart Douglas D Vitolo Umberto U Zaja Francesco F Zhang Qingyuan Q Mattiello Federico F Sellam Gila G Punnoose Elizabeth A EA Szafer-Glusman Edith E Bolen Christopher R CR Oestergaard Mikkel Z MZ Fingerle-Rowson Guenter R GR Nielsen Tina T Trneny Marek M

Blood 20190107 9

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 assess ...[more]

PMID: 30617197

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Project description:Background/objectivesPrognostic indices rarely include cognition. We determined if a comprehensive cognitive screen or brief individual items were associated with improved mortality predictions of a widely used prognostic index.Design, setting, and participantsThe National Social Life Health and Aging Project Wave 2, a nationally representative, cross-sectional, in-home survey conducted in 2010 to 2011 on 3,199 community-dwelling adults aged 60 to 99 years.MeasurementsCognition was measured using a Survey-Adapted Montreal Cognitive Assessment (MoCA-SA) grouped into three screened categories: screen normal (≥24 points), screen positive for mild cognitive impairment (18-23 points), and screen positive for dementia (<18 points). Single-item cognitive measures included clock-draw and five-word delayed recall. We constructed a modified Lee Prognostic Index (range = 0-18 points) based on age, behavior, function, and comorbidities shown to predict long-term mortality. We used logistic regression and the fraction of new information provided to determine if each cognitive measure improved the Lee index's 5-year mortality prediction.ResultsThe sample was 54% female and had a mean age of 72 years, MoCA-SA score of 22 (SD = 4.5), and Lee index of 7 (SD = 3). Regression analysis indicated the MoCA-SA modestly improved the Lee index's mortality prediction (P < .001; fraction of new information provided = 0.06); for low Lee index scores (<4 points), the absolute mortality rate difference was 7% by cognitive status; and for higher Lee index scores (4-7 points or 8-12 points), the absolute mortality rate difference was 15% by cognitive status. The clock-draw and delayed-recall items added similar value to mortality predictions as the longer MoCA-SA. Cognition had the third highest fraction of new information of all 13 Lee index items.ConclusionIncorporating a brief measure of cognition into a modified Lee index, even with single items, resulted in more accurate 5-year mortality risk predictions. Cognition should be included in prognostic calculators in older adults given its independent association with mortality risk. J Am Geriatr Soc 68:1796-1802, 2020.

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Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL.

Publications

Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL.

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