Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP

Author:

Malumbres Raquel1,Chen Jun1,Tibshirani Rob2,Johnson Nathalie A.3,Sehn Laurie H.4,Natkunam Yaso5,Briones Javier6,Advani Ranjana7,Connors Joseph M.4,Byrne Gerald E.8,Levy Ronald7,Gascoyne Randy D.3,Lossos Izidore S.1

Affiliation:

1. Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, FL;

2. Department of Health Research and Policy, and Statistics, Stanford University, CA;

3. Department of Pathology,

4. Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC;

5. Department of Pathology, Stanford University School of Medicine, CA;

6. Department of Clinical Hematology, Hospital Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain;

7. Department of Medicine, Division of Oncology, Stanford University School of Medicine, CA; and

8. Department of Pathology, University of Miami, FL

Abstract

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by variable clinical outcomes. Outcome prediction at the time of diagnosis is of paramount importance. Previously, we constructed a 6-gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies. However, the standard therapy has evolved into rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Herein, we evaluated the predictive power of a paraffin-based 6-gene model in R-CHOP–treated DLBCL patients. RNA was successfully extracted from 132 formalin-fixed paraffin-embedded (FFPE) specimens. Expression of the 6 genes comprising the model was measured and the mortality predictor score was calculated for each patient. The mortality predictor score divided patients into low-risk (below median) and high-risk (above median) subgroups with significantly different overall survival (OS; P = .002) and progression-free survival (PFS; P = .038). The model also predicted OS and PFS when the mortality predictor score was considered as a continuous variable (P = .002 and .010, respectively) and was independent of the IPI for prediction of OS (P = .008). These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE tissue from initial diagnostic biopsies.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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