ViPOR Achieves Lasting Remission in Certain Lymphoma Subtypes

On June 20, 2024, researchers unveiled important findings about a promising treatment for certain subtypes of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in the New England Journal of Medicine. The study, led by Dr. Christopher Melani from the National Cancer Institute in Bethesda, Maryland, explored the efficacy of a combination therapy named ViPOR, which includes venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide.

The study was conducted in a single medical center and spanned two phases: a phase 1b and a phase 2. In phase 1b, 20 patients participated, with 10 specifically diagnosed with DLBCL. This phase was primarily focused on determining the optimal dose of venetoclax, which was established at 800 mg. Subsequently, phase 2 included 40 patients with either germinal-center B-cell (GCB) or non-GCB DLBCL subtypes.

The results of the study revealed that all patients in phase 2 experienced some form of toxic effects. Neutropenia, thrombocytopenia, anemia, and febrile neutropenia were observed in 24%, 23%, 7%, and 1% of the treatment cycles, respectively. Despite these side effects, the therapy showed significant promise. Among the evaluable patients with DLBCL, 54% had objective responses to the treatment. More notably, 38% of the patients achieved complete responses, particularly those with non-GCB DLBCL and high-grade B-cell lymphoma characterized by rearrangements in MYC and BCL2 or BCL6 genes, or both.

An important marker of the therapy's effectiveness was the disappearance of circulating tumor DNA in 33% of the patients at the end of the ViPOR treatment. In terms of long-term outcomes, the study reported a two-year progression-free survival rate of 34% and an overall survival rate of 36%, with a median follow-up duration of 40 months.

The researchers highlighted that while ViPOR's effectiveness is notably higher in specific molecular subtypes of DLBCL, this specificity bolsters confidence in the broader applicability of the results. They acknowledged that the study's scope was limited to certain subgroups of DLBCL patients, but the outcomes suggest that ViPOR could be a viable treatment option for those with potentially curable disease subtypes.

The study was supported by contributions from pharmaceutical companies, with Genentech providing venetoclax and obinutuzumab, and Bristol Myers Squibb-Celgene supplying lenalidomide. This collaborative effort underscores the importance of partnerships in advancing medical research and developing new therapies for challenging diseases like DLBCL.