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CD5 Biomarker Effective for Identifying DLBCL Subtypes Sensitive to BTK Inhibitor Therapy
A novel study demonstrated that CD5 gene expression signature (CD5sig) is a useful biomarker to identify diffuse large B-cell lymphoma (DLBCL) subtypes vulnerable to BTK inhibitor therapies, and complements current biomarker approaches.
Investigators performed CD5 immunohistochemistry (IHC) on 404 DLBCLs to identify CD5 IHC+ and CD5 IHC– cases, which were subsequently characterized at the molecular level through mutational and transcriptional analyses.
A 60-gene CD5sig was constructed using genes differentially expressed between CD5 IHC+ and CD5 IHC– non-germinal center B-cell-like (non-GCB) DLBCL subtypes. This CD5sig was applied to external DLBCL data sets, which included pretreatment biopsies from patients enrolled in the phase 3 PHOENIX study. This defined the extent to which the CD5sig could identify non-GCB DLBCL subtypes that benefited from the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
Results demonstrated that CD5 expression was observed in 12% of non-GCB DLBCL types. It was also noted that CD5+ DLBCL types displayed transcriptional features of B-cell receptor (BCR) activation and were enriched for BCR-activating mutations which are known to correlate with BTK inhibitor sensitivity.
Study researchers concluded, “CD5sig is a useful biomarker to identify DLBCLs vulnerable to BTKi-based therapies and complements current biomarker approaches by identifying DLBCLs with genetic and nongenetic bases for BTKi sensitivity.”
Source:
Cooper A, Tumuluru S, Kissick K, et al. CD5 gene signature identifies diffuse large b-cell lymphomas sensitive to brutonʼs tyrosine kinase inhibition. Journal of Clinical Oncology. Published online December 11, 2023. doi: 10.1200/JCO.23.01574
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