Clinical Edge

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Gene Expression Signature Reveals High-Grade GCB DLBCL

Key clinical point: A gene expression signature may distinguish high-grade diffuse large B-cell lymphomas (DLBCLs) from other germinal center B-cell–like DLBCLs.

Major finding: The 5-year time to progression rate was 81% in patients who were double-hit gene signature–negative and 57% in those who were double-hit gene signature–positive (P less than .001).

Study details: A discovery cohort of 157 patients and two validation cohorts of 262 and 162 patients each.

Disclosures: This research was supported by the Canadian Cancer Society Research Institute and other organizations. The researchers reported relationships with various pharmaceutical companies.


Scott DW et al. J Clin Oncol. 2019 Jan 20;37(3):190-201.


Dr. David Henry, Editor in Chief of MDedge Hematology/Oncology, comments:

The scientific explosion in the pathology department has been wonderful, but we are becoming victims of our own success. Long ago, our non-Hodgkin lymphoma patients were simply high-grade, intermediate grade, or low grade and that was enough for prognosis and therapy. Now, we have the pathology and genetic/gene determination expression and flow cytometry. While this has greatly helped to inform subtle differences in prognosis and therapeutic outcome between intermediate- to high-grade lymphomas, this is still an area that could benefit from tighter classification.

The MYC, BCL2, and BCL6 define the triple hit phenotype and is one of our worst DLBCL types. Thanks to the authors of this paper in the Journal of Clinical Oncology, we have something that may help better subdivide these patients called the DHITsig or double hit gene signature test. The DHITsig is based on an analysis of 104 genes that were most often expressed and might help differentiate between higher and lower DLBCL profiles. For example, the 5-year time to progression was 81% in patients who were DHITsig negative versus 57% in those who were positive. The 5-year overall survival was 81% versus 60%, and both of these results were statistically significant (P= .001). The authors went on to replicate their results in a validation cohort and found the same results.

Hopefully, tests like this will make their way into clinical trials and into our clinics where we can better differentiate prognosis and dictate appropriate therapy to improve the outcomes in these highly aggressive DLBCL non-Hodgkin lymphomas.