NIH: Non-Chemo Drug Combo Yields Lasting Remission in DLBCL

Researchers from the National Institutes of Health (NIH) have discovered a new non-chemotherapy treatment regimen for relapsed diffuse large B-cell lymphoma (DLBCL). This innovative approach has shown promising results, including full remission in some patients who had previously stopped responding to standard treatments.

The findings were published in The New England Journal of Medicine, where NIH scientists detailed their combination of five anti-cancer agents: AbbVie and Genentech’s Venclexta (venetoclax), Johnson & Johnson’s Imbruvica (ibrutinib), Genentech’s Gazyva (obinutuzumab), Bristol Myers Squibb’s Revlimid (lenalidomide), and the corticosteroid prednisone. This regimen, named ViPOR, was evaluated in a Phase Ib/II study involving 50 patients diagnosed with DLBCL.

The results were striking. In 28 out of 48 evaluable patients, the investigational regimen significantly reduced tumor size, which translates to a 54% objective response rate. Furthermore, 18 patients experienced complete tumor disappearance, equating to a 38% complete response rate for ViPOR. By the end of the treatment, circulating tumor DNA became undetectable in 33% of the patients. During a follow-up period extending two years post-treatment, 34% of patients showed no evidence of the disease, and 36% remained alive.

Regarding safety, the Phase Ib study found only one dose-limiting incident of grade 3 intracranial hemorrhage. In the Phase II portion, notable adverse events included grade 3 or 4 neutropenia, thrombocytopenia, anemia, and febrile neutropenia.

Christopher Melani, a researcher from the National Cancer Institute’s Center for Cancer Research and a co-leader of the study, commented on the genetic complexity of DLBCL. He highlighted the difficulty in identifying the most effective drug combination for individual patients. By incorporating five drugs, the researchers believe they can find an effective combination against each patient's specific tumor.

The NIH team is now planning a larger Phase II study to be conducted across multiple centers. This mid-stage trial will evaluate the efficacy of ViPOR in different genetic subtypes of DLBCL.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, accounting for about 25% to 30% of cases. Characterized by enlarged lymph nodes or rapidly growing masses in nodal or extranodal sites, DLBCL is generally aggressive. However, it often responds well to the R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

Various pharmaceutical companies are actively working on developing superior therapies for DLBCL. These efforts aim to enhance safety and efficacy while providing more options for patients, particularly those who experience disease progression or cannot tolerate current treatments. For example, Pfizer is advancing its antibody-drug conjugate Adcetris (brentuximab vedotin), which, according to a March 2024 report, significantly improved survival in the Phase III ECHELON-3 study. Similarly, Roche is pursuing DLBCL treatment with its bispecific T-cell engager Columvi (glofitamab), which demonstrated improved survival in the Phase III STARGLO trial as per an April 2024 readout.

These developments represent significant advancements in the treatment landscape for DLBCL, offering hope for better patient outcomes and effective management of this challenging form of lymphoma.