Next Steps for Validating CD5 IHC Positive DLBCL Types Benefiting From Targeted Therapies

Alan Cooper, BS, Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, shared follow-up research steps that would seek to validate CD5 immunohistochemistry (IHC) positive diffuse large B-cell lymphomas (DLBCL) that could benefit from specific targeted therapies influencing the B-cell receptor signaling pathway. 

Transcript:

Hi, I'm Alan Cooper. I'm a research assistant in Dr. Kline’s lab at the University of Chicago, where I've focused on lymphoma for the past 3 years. I think what our study shows nicely is that we can use transcriptional signatures, one based on CD5 [immunohistochemistry] (IHC) positive DLBCLs, to pull in patients with a genetic and a non-genetic basis to sensitivity to a targeted therapy [which is] ibrutinib. On the question of CD5 and sensitivity to BTK inhibitors, future work would really seek to validate that CD5 IHC positive DLBCLs could benefit from other therapies that perturb the B-cell receptor signaling pathway. 

Second generation BTK inhibitors come to mind most concretely, many of which are less toxic than ibrutinib and could have efficacy in older patients. [The] PHOENIX [trial] failed to show a benefit that being second generation BTK inhibitors like acalabrutinib and zanubrutinib. There are other non-BTK inhibitors, other agents that target the B-cell receptor pathway, which may also be interesting to investigate as to whether our CD5 gene signature or CD5 immunohistochemistry can identify them as benefiting agents, like bortezomib.

It's been newly established in DLBCL, but novel agents like the CD79b-targeting antibody drug conjugate, polatuzumab vedotin, may, at least in subset analysis in the secondary analysis, show a particular benefit among [activated B-cell] (ABC) DLBCL patients. I think it would be equally warranted to evaluate CD5 immunohistochemistry in that setting as well.

Source:

Cooper A, Tumuluru S, Kissick K, et al. CD5 gene signature identifies diffuse large b-cell lymphomas sensitive to brutonʼs tyrosine kinase inhibition. J Clin Oncol. Published online December 11, 2023. doi: 10.1200/JCO.23.01574