Exploring Treatment With ViPOR in Mantle Cell Lymphoma

National Cancer Institute expert, Christopher J. Melani, MD, discusses the synergy of 5 drugs that make up a targeted therapy regimen for patients with 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.