Novel Combination Therapy Impresses With Safety/Efficacy in DLBCL


Christopher J. Melani, MD, discusses updated data from the phase 1b/2 ViPOR trial of the combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, in patients with diffuse large B-cell lymphoma.

Christopher J. Melani, MD, assistant research physician in the Lymphoid Malignancies Branch at the Center for Cancer Research, National Cancer Institute, discusses updated data from the phase 1b/2 ViPOR trial (NCT03223610) of the combination of venetoclax (Venclexta), ibrutinib (Imbruvica), prednisone, obinutuzumab (Gazyva), and lenalidomide (Revlimid), in patients with diffuse large B-cell lymphoma (DLBCL).

According to Melani, the combination, which is given in short, non-continuous cycles, showed promising safety and efficacy results and was well-tolerated across all ages. A total of 38% of patients achieved complete remission (CR), and these rates were even higher in certain subtypes.

While further research is needed, the ViPOR study represents a potentially transformative approach for patients with DLBCL.


0:10 | I presented data for the relapsed/refractory cohort of the ViPOR study. ViPOR is a novel combination targeted therapy regimen building on some of the synergy that we've seen in preclinical studies of DLBCL, combining several agents that target B-cell receptor signaling, such as ibrutinib, prednisone, as well as lenalidomide, in addition to venetoclax, which targets BCL2 and apoptosis, and obinutuzumab which facilitates innate immunity through CD20. It really is a novel concept because it's modeled after cytotoxic chemotherapy, where all of the targeted agents are given in non continuous cycles, so 2 weeks of study drug, 1 week break for a fixed duration. So only 6 cycles or 18 weeks without any maintenance therapy.

0:53 | What was impressive regarding this regimen is 1: it was extremely safe and tolerable for patients of all ages, even upwards into their 80s, compared [with] other types of regimens such as cytotoxic chemotherapy, and it was very effective.

1:10 | Overall the rate of complete remission was 38% in patients with relapsed/refractory large cell [lymphoma], with a median line of therapy of 3. In some subtypes, such as the ABC or non GCB subtype of diffuse large B-cell lymphoma, as well as high grade B-cell lymphoma double-hit BCL2, the CR rates were in the 62% and 53% range, respectively. Despite the time-limited therapy of only 6 cycles, these remissions were very durable. Overall, our 2-year progression-free survival was 34%. In double-hit, it was 47%, and in high-grade B-cell lymphoma, it was 38% and a median follow-up of 40 months. These were very deep and durable remissions, despite a very fixed limited therapy.

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