Dr. D’Angelo on Emerging Therapies in DLBCL

Christopher R. D’Angelo, MD, assistant professor, Division of Hematology & Oncology, The University of Nebraska Medical Center, discusses emerging therapies in diffuse large B-cell lymphoma (DLBCL).

In the genomic landscape of DLBCL, some pathways have been identified as attractive and hyperactive targets, D’Angelo says. For instance, proteolysis targeting chimeras (PROTACs), an evolving therapy in DLBCL, were presented in a discussion of a phase 1 study (NCT04830137) at the 2022 ASCO Annual Meeting, D’Angelo notes.

PROTACs work by linking a target to a cell’s E3 ubiquitin ligase recruiting ligand, a proteasome degradation system, which causes a more thorough degradation of the target than binding agents do, D’Angelo explains. PROTACs have been used to target and degrade BTK, offering a potential advantage over covalent and noncovalent BTK inhibitors, D’Angelo says.

The phase 1 trial is currently recruiting patients with a variety of B-cell non-Hodgkin lymphomas, including DLBCL, D’Angelo notes. PROTACs have displayed preliminary efficacy in non-germinal center B-cell–like DLBCL, and further findings in that population and others are awaited, D’Angelo concludes.