A non-chemotherapy treatment has been created by researchers at the National Institutes of Health (NIH) that has shown promising results in achieving full remissions for individuals with aggressive B-cell lymphoma that has returned or is not responding to standard treatments. This five-drug combination targets multiple molecular pathways that diffuse large B-cell lymphoma (DLBCL) tumors use to survive.
A combination of drugs known as ViPOR was tested in a clinical trial at the NIH’s National Cancer Institute. This combination targets multiple molecular pathways that diffuse large B-cell lymphoma (DLBCL) tumors use to survive. The trial included 50 patients with DLBCL, the most common type of lymphoma. The treatment resulted in substantial tumor shrinkage in 26 of 48 (54%) evaluable patients, with 18 (38%) of those patients experiencing a complete response, meaning their tumors disappeared entirely. At two years, 36% of all patients were alive and 34% were free of disease. These findings demonstrate the promising benefits of the treatment.
The article discusses a study published in the New England Journal of Medicine on June 20, 2024, which found that certain subtypes of DLBCL are more likely to be seen in patients. Dr. Christopher J. Melani of NCI’s Center for Cancer Research, who co-led the study, noted that many patients who had stopped responding to standard treatments were still alive after two to four years. This is a significant improvement from the previous prognosis, which would have seen these patients succumb to the disease within a year. The study also identified genetic pathways involved in the development and progression of the disease.Survival of the various molecular subtypes of DLBCL, such as activated B cell-like (ABC) DLBCL and germinal center B cell-like (GCB) DLBCL, is a challenge. Targeted drugs have been effective in inhibiting certain pathways, but individual drugs often do not result in lasting responses in patients due to tumor resistance from alternative survival pathways. Dr. Melani and his team believed that combining targeted drugs to block multiple survival pathways would lead to more enduring responses.
In their laboratory studies, they analyzed which targeted drugs could be best combined to synergistically kill DLBCL cells.The scientists developed a treatment plan using five different drugs for testing on human subjects. In order to ensure that the drugs would work together effectively, they administered them simultaneously in two-week cycles, with a weeklong break in between to minimize side effects. According to Dr. Melani, the genetic diversity of DLBCL makes it difficult to determine the most effective drug combination for each patient. However, by combining five drugs, they hope to find a combination that works well for the majority of patients.
The ViPOR regimen, consisting of six cycles, was administered to 50 individuals with relapsed or refractory DLBCL in a phase 1b/2 trial. The effectiveness of ViPOR varied based on the subtype of DLBCL, with complete responses being more prevalent in non-GCB DLBCL and high-grade B-cell lymphoma “double hit” subtype of GCB DLBCL. Specifically, 62% of individuals with non-GCB DLBCL and 53% of those with double-hit GCB DLBCL subtype demonstrated a complete response to ViPOR. After two years, both progression-free and overall survival rates were found to be higher in individuals with non-GCB DLBCL and double-hit GCB DLBCL.
Compared with others in the study, individuals with non-GCB DLBCL and double-hit GCB DLBCL demonstrated a stronger reliance on the survival mechanisms targeted by ViPOR. As a result, they exhibited a particularly positive response to the combination therapy. ViPOR also contributed to achieving lasting remissions in 6 out of 20 (30%) patients with lymphomas that had not responded to or had recurred after CAR T-cell therapy, which is the current standard of care for individuals with relapsed DLBCL.
The side effects of the five-drug regimen were generally mild to moderate when compared to those of standard treatments, and they improved during treatment breaks. Only five patients had to discontinue the treatment prematurely.The researchers mentioned that ViPOR may have additional drugs added to improve its effectiveness due to its mild to moderate side effects. They are also looking into using the ViPOR regimen for other types of lymphoma that have not responded to previous treatments. A larger phase 2 study is being developed to verify the effectiveness of ViPOR in people with non-GCB DLBCL and double-hit GCB DLBCL at multiple centers. More research is needed to develop treatments for GCB DLBCL subtypes that are not as responsive to ViPOR. The NCI’s Center for Cancer is involved in this research.Research scientists Wyndham H. Wilson, M.D., Ph.D., Mark Roschewski, M.D., and Louis M. Staudt, M.D., Ph.D., worked together on the study with Dr. Melani. Other researchers from NIH’s National Center for Advancing Translational Sciences and other institutions also took part in the study.
