AACR 2023: Identifying a CD5 Gene Signature for Sensitivity to BTK Inhibition in DLBCL

By: Joshua Swore, PhD
Posted: Monday, May 1, 2023

Expression of CD5 may prove to be a useful biomarker for identification of high-risk diffuse large B-cell lymphoma (DLBCL), according to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 4330/5). “By employing a newly defined genetic classification algorithm (LymphGen), distinct genetic DLBCL subtypes that benefit from [Bruton’s tyrosine kinase (BTK)] inhibitors were identified,” said Justin Kline, MD, of the University of Chicago, and colleagues. “However, LymphGen is not utilized in the clinic and fails to classify more than 40% of DLBCLs. To overcome these challenges, we sought to identify a straightforward biomarker of BTK inhibitor sensitivity."

The researchers used immunohistochemistry with 405 samples of DLBCL. They then compared the transcriptomes of CD5-positive and CD5-negative DLBCLs to identify a CD5 signature. This signature was then compared with genomic data sets that included 584 pretreatment biopsies to evaluate the signatures’ ability to predict treatment response.

The group identified 27 CD5-positive DLBCL samples via immunohistochemistry and confirmed they were of nongerminal B-cell origin. These samples contained upregulated genes related to B-cell receptor signaling with increased B-cell receptor–activating mutations. Transcriptomic analysis identified a repertoire of 60 upregulated genes in CD5-positive B cells compared with CD5-negative B cells.

Applying the panel to the external genomic data sets, the investigators discovered that 15% of cases were enriched with B-cell receptor–activating mutations. It was also revealed that DLBCLs were absent mutations known to induce resistance to BTK inhibition. Finally, the authors noted that when the CD5-positive gene signature was applied to the phase III Phoenix study, patients with DLBCL benefited in terms of event-free and overall survival.

Disclosure: For full disclosures of the study authors, visit www.abstractsonline.com.

AACR Annual Meeting 2023

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