Exploring Treatment With ViPOR in Mantle Cell Lymphoma

Christopher J. Melani, MD, assistant research physician, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, breaks down the mechanisms of a 5-drug investigational regimen being explored for the treatment of patients with mantle cell lymphoma (MCL).

In a phase 1b/2 clinical trials, the combination of venetoclax (Venclexta), ibrutinib (Imbruvica), prednisone, obinutuzumab (Gazyva), and lenalidomide (Revlimid) or ViPOR, is assessed for safety and efficacy outcomes.

Transcription:

0:08 | What Viper is, is it's a novel combination targeted therapy regimen that simultaneously hits multiple key survival pathways utilized by B-cell lymphomas for growth and survival. So, you know, it's an acronym. So, it includes the BCL2 inhibitor, Venetoclax, which works on apoptosis, and BCL2 is an anti-apoptotic protein, so blocking induces apoptosis in the cells.

0:35 | Ibrutinib is an inhibitor of the Bruton’s tyrosine kinase, which is an enzyme in the B-cell receptor signaling pathway and is important for mantle cell lymphoma. P is prednisone, which is a corticosteroid, which is often in many regimens such as R-CHOP, which is a combination chemo regimen, which is a mechanism of genotoxic stress for the lymphoma cells.

0:58 | Obinutuzumab is the CD20. It's a type-2 novel glycoengineered CD20 antibody similar to rituximab [Riuxan], promoting innate immunity towards the B-cell lymphoma. The ‘r’ is Revlimid or lenalidomide, which through its effect on transcription factors, also leads to decreased signaling in certain pathways.

1:21 | So, the NF-κB pathway also promotes interferon-mediated cell death. So, we showed that this combination of 5 drugs was very synergistic killing lymphoma in the lab, in cell lines, and xenograft models. And this is the first study that's actually combining all 5 of these targeted agents, which are all active in B-cell lymphomas given in humans.