Christopher J. Melani, MD, discusses the combination investigated in the ViPOR study of patients with relapsed/refractory or untreated mantle cell lymphoma.
Christopher J. Melani, MD, assistant research physician in the Lymphoid Malignancies Branch at the Center for Cancer Research, National Cancer Institute, discusses the combination investigated in the ViPOR study (NCT03223610) of patients with relapsed/refractory or untreated mantle cell lymphoma (MCL).
According to Melani, previous trials have examined Bruton's tyrosine kinase (BTK) inhibitors, single-agent ibrutinib, the EPOCH-R regimen, consisting of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab, and more, across multiple lymphoma types.
Data from these previous studies led to this phase 1b/2 clinical trial which aimed to assess the ViPOR regimen, consisting of venetoclax (Venclexta), ibrutinib (Imbruvica), prednisone, obinutuzumab (Gazyva), and lenalidomide (Revlimid). Investigators looked to evaluate the safety and efficacy of this combination in several disease types, including MCL.
0:08 | A lot of the data that led to the development of this regimen was done in the activated B-cell subtype of diffuse large B-cell lymphoma, so we did a lot of the original studies using single-agent ibrutinib. We showed that ibrutinib is effective in relapsed/refractory large cell lymphoma, and it was more active with a response of about 37% to 38% in patients with the activated B-cell subtype vs the germinal center subtype where there was only about a 5% response rate.
0:35 | We did present data using a newer BTK inhibitor called acalabrutinib [Calquence] in untreated large B-cell disease and we are finding that other types of diffuse large B-cell lymphomas, such as the germinal center, do have activity and double-hit and diffuse large B-cell lymphoma. There is an activity of BTK. But historically, we thought it to be more active in the ABC [activated B-cell] subtype. Building on that study, we did a lot of preclinical testing and we worked with a collaborator to do high synergy screening of BTK inhibitors with multiple molecules of all different types. Some of the key agents that were shown to be the most synergistic with ibrutinib or BTK inhibitors were BCL2 inhibitors, so venetoclax as well as immune-modulatory agents such as lenalidomide. Those 3 key components were very synergistic together, meaning that the effect was not just additive, it was a greater effect than would be expected with just an additive benefit of both.
1:42 | We initially combined ibrutinib, and lenalidomide with chemotherapy, in EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab] in the relapsed/refractory setting of diffuse large B-cell lymphoma. Building upon that, because many of these relapsed/refractory lymphoma patients are resistant or refractory to chemotherapy, we ended up taking out the chemotherapy keeping the steroid and the CD20 antibody, and then added in venetoclax, which again was very synergistic. We originally did that in diffuse large B-cell lymphoma, follicular lymphoma, and other non-Hodgkin lymphomas, because there is a risk of tumor lysis that is higher with either chronic lymphocytic lymphoma [CLL] or mantle cell lymphoma.