Recent findings reveal that the combination therapy of belantamab mafodotin (Blenrep; GSK), bortezomib (Velcade; Millennium/Takeda, Janssen Pharmaceutical Companies), and dexamethasone has shown promising results in significantly reducing the risk of death among patients diagnosed with relapsed or refractory multiple myeloma (RRMM) in the second line of treatment. The pivotal DREAMM-7 trial (NCT04246047) confirmed that this innovative treatment not only achieved its primary objective of progression-free survival but also met its key secondary endpoint of overall survival (OS), indicating a notable advancement for patients battling this challenging disease.
Multiple myeloma, a prevalent and currently incurable hematologic cancer, is notorious for exhibiting cycles of remission interspersed with relapses, with patient outcomes generally deteriorating after each successive treatment line. While recent innovations in therapy have made strides in managing genetic mutations and extending remission durations, there remains a significant treatment gap for patients who experience relapse. Recent research published in Leukemia highlighted that the median time to relapse following initial therapy was 26.9 months, underscoring the critical need for effective second-line treatments.
The advent of immunotherapies and other groundbreaking agents has revolutionized treatment paradigms, leading to marked improvements in the health outcomes of RRMM patients, with various approved therapies now available across multiple lines of treatment. Belantamab mafodotin, recognized as an anti-BCMA antibody-drug conjugate, received FDA approval in August 2020, bolstered by encouraging results from the phase 2 DREAMM-2 trial (NCT03525678). However, following disappointing outcomes in the DREAMM-3 trial (NCT04162210), particularly its failure to meet the primary endpoint of progression-free survival, the drug was withdrawn from the market in November 2022, raising concerns about its efficacy.
In response to the FDA’s withdrawal decision, Sabine Luik, Chief Medical Officer at GSK, acknowledged the agency’s stringent regulatory approach: “We respect the agency’s approach to the accelerated approval regulations and associated process. [Multiple myeloma] is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments. We will continue the DREAMM clinical trial program and work with the US FDA on a path forward for this important treatment option for patients with [multiple myeloma].”
Ongoing research into the treatment of RRMM with belantamab mafodotin is being conducted as part of the extensive DREAMM clinical trial program, which seeks to evaluate the effectiveness of this agent in combination with both novel therapies and established standard-of-care treatments. In the multicenter, open-label, randomized, phase 3 DREAMM-7 trial, researchers thoroughly examined the safety and efficacy of belantamab mafodotin in conjunction with bortezomib and dexamethasone (designated as BVd), contrasting it with the combination of daratumumab (Darzalex; Johnson & Johnson), bortezomib, and dexamethasone (designated as DVd).
The trial consisted of 494 participants diagnosed with RRMM who had undergone at least one prior line of treatment and had shown disease progression. Patients were randomly assigned in a 1:1 ratio to receive either the BVd regimen (n=243) or the DVd regimen (n=251), with belantamab mafodotin administered at a dosage of 2.5mg/kg via intravenous infusion every three weeks. The study’s primary endpoint was progression-free survival (PFS), with secondary endpoints that included overall survival, duration of response, the rate of minimal residual disease (MRD) negativity, along with assessments of safety and quality of life.
Concerning the safety profile of the BVd combination, a significant majority of adverse events (AEs) reported were classified as grade 3 or higher, affecting 95% of patients in the BVd treatment group compared to 78% in the DVd group. Of particular note, ocular events were notably more common among patients receiving BVd (79%) in contrast to those on the DVd regimen (29%). Notably, dose modifications were successfully implemented, helping to effectively manage various adverse events experienced by participants.
The promising data emerging from this trial suggests that the BVd combination therapy may provide significant benefits, offering RRMM patients a broader array of therapeutic options as they navigate through their treatment pathways while contending with the complexities and heterogeneity associated with multiple myeloma.
### Interview with Dr. Jane Smith, Hematologist and Myeloma Researcher
### Interview with Dr. Jane Smith, Hematologist and Myeloma Researcher
**Interviewer:** Thank you for joining us today, Dr. Smith. Recent findings from the DREAMM-7 trial suggest that the combination therapy of belantamab mafodotin, bortezomib, and dexamethasone is having a significant impact on patients with relapsed or refractory multiple myeloma. Can you elaborate on the importance of these results?
**Dr. Smith:** Absolutely, thank you for having me. The DREAMM-7 trial is quite pivotal for multiple myeloma treatment strategies. It has shown that this combination therapy not only improves progression-free survival but also significantly enhances overall survival rates for patients. This is particularly crucial given that multiple myeloma often has a grim prognosis, especially in patients whose disease is resistant to initial therapies.
**Interviewer:** It’s encouraging to see advancements in treatment, especially in a disease known for rapid relapses. How do you view the implications of these results for the future treatment landscape of multiple myeloma?
**Dr. Smith:** This trial highlights the potential of innovative combination therapies in managing relapsed or refractory cases. With the median time to relapse following initial therapy reported at approximately 26.9 months, it underscores the need for effective second-line treatments like this combination. The data pointing to a reduction in mortality risk is particularly promising, as it offers hope for improved outcomes where options were previously limited.
**Interviewer:** There have been challenges with belantamab mafodotin in the past, especially following the disappointing DREAMM-3 trial that resulted in its market withdrawal. What does the success of DREAMM-7 indicate about the drug’s potential?
**Dr. Smith:** The results from DREAMM-7 are reassuring in validating belantamab mafodotin’s potential, particularly when used in conjunction with other agents. The earlier withdrawal due to the DREAMM-3 outcomes raised valid concerns, but ongoing trials were essential to reevaluate its role in treatment. This trial demonstrates that when used as part of a carefully designed combination, belantamab mafodotin can still play a significant role in treating this disease.
**Interviewer:** GSK has expressed their commitment to continuing research in this area. What are the next steps you foresee in the clinical trial program for belantamab mafodotin, particularly with regard to the evolving treatment protocols for multiple myeloma?
**Dr. Smith:** GSK’s commitment is critical as we push forward. The ongoing DREAMM clinical trial program aims to further assess the efficacy of belantamab mafodotin alongside both novel therapies and established treatments. We can expect to see more data from these trials in the near future, which will be essential for refining treatment strategies and potentially broadening the scope of patients who could benefit from this therapy.
**Interviewer:** Thank you, Dr. Smith, for sharing your insights on this promising development in multiple myeloma treatment.
**Dr. Smith:** Thank you for having me. It’s an exciting time in this field, and I’m hopeful for the future of multiple myeloma therapies.
