ViPOR Study for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Mark Roschewski, a clinical investigator specializing in lymphoma at the National Cancer Institute in Bethesda, Maryland, presented three exciting abstracts at the ASH meeting, shedding light on groundbreaking developments in lymphoma treatment. One of the notable presentations focused on the updated Phase 2 results of a regimen known as ViPOR, designed for patients with relapsed (returning) and refractory (not responding) diffuse large B-cell lymphoma (DLBCL).

Combined Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide for DLBCL

Significant research has identified biological pathways that cause DLBCL, leading to the creation of drugs that focus on targeting these specific cancer survival pathways. Although these drugs can work on their own, they usually don't result in strong responses or cure the disease.

Developed at the National Cancer Institute, the ViPOR regimen is distinctive as it consists of multiple targeted agents, including venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide. All these medications are known to treat large cell lymphoma, and when combined, they work together to create a greater effect. ViPOR targets major survival pathways in B-cell lymphomas including BCL-2 (apoptosis), BTK (B-cell receptor signaling and NFKB), Cereblon (NFKB), and CD20.

Unlike traditional chemotherapy for DLBCL, ViPOR involves six cycles, each lasting three weeks, with patients receiving therapy for only two out of every three weeks. Importantly, the regimen does not include a higher dose phase called consolidation or the long-term low dose phase called maintenance. The 21-day cycle is as follows:

1. Venetoclax (Venclexta) in increasing amounts over 12 days (maximum tolerated dose determined in phase I)
2. Ibrutinib (Imbruvica) 560 mg by mouth on days 1-14
3. Prednisone 100 mg by mouth on days 1-7
4. Obinutuzumab (Gazyva) 1000 mg through IV days 1-2
5. Lenalidomide (Revlimid) 15 mg by mouth days 1-14

Preliminary Study Results

The phase 2 results presented by Chris Melani, a colleague of Mark Roschewski, showcased the regimen's remarkable success. Fifty patients were enrolled in the ViPOR study with a median age of 61. Almost all patients had stage 3-4 DLBCL and had been previously treated with other therapies. Nearly 40% of patients achieved a complete response, and these responses lasted for up to two years. Particularly encouraging was the observation that specific subtypes of large cell lymphomas exhibited more favorable responses. These two subtypes are non-GCB DLBCL and HGBCL-DH-BCL2. Additionally, patients who could not tolerate or who were refractory to standard chemoimmunotherapy responded well to ViPOR. 

The absence of standard approaches like CAR T-cell therapy makes ViPOR a unique and promising alternative.

ViPOR May Become a DLBCL Treatment Option

The data presented at ASH suggest that ViPOR, with its unique combination of targeted agents, might offer a potential cure for patients even without resorting to conventional methods like CAR-T therapy. The regimen's efficacy (effectiveness) and durability in achieving complete responses signify a significant stride forward in lymphoma treatment.

Roschewski mentions that these findings pave the way for ongoing multi-center studies, aiming to validate and further enhance the outcomes of the ViPOR regimen. If successful, ViPOR could emerge as a transformative treatment option for DLBCL.

This study is still enrolling patients who meet the inclusion and exclusion criteria, including adults 18 and older with relapsed or refractory B-cell lymphomas. You can learn more about eligibility here.

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