GSK's antibody-drug conjugate (ADC) Blenrep (belantamab mafodotin) is poised for a potential comeback after demonstrating a significant overall survival benefit in a Phase 3 trial for relapsed or refractory multiple myeloma. The DREAMM-7 study revealed that Blenrep, when combined with bortezomib and dexamethasone (BorDex), reduced the risk of death by 42% compared to daratumumab plus BorDex, a standard-of-care treatment. These findings, presented at the American Society of Hematology (ASH) annual meeting, could redefine the treatment landscape for patients with multiple myeloma at or after their first relapse.
DREAMM-7 Trial Results
The DREAMM-7 trial (n=494) compared Blenrep in combination with bortezomib and dexamethasone (BVd) to daratumumab in combination with bortezomib and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma. The study met its key secondary endpoint of overall survival (OS), indicating a significant reduction in the risk of death compared to the standard of care. With a median follow-up of 39.4 months, the projected median OS for BVd was 84 months, compared to 51 months for DVd (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). The three-year OS rate was 74% in the BVd arm and 60% in the DVd arm.
"The overall survival results from the DREAMM-7 trial underscore the potential for this Blenrep combination to extend the lives of patients with r/r MM," said Hesham Abdullah, global head of oncology R&D at GSK. "This is a statistically significant and clinically meaningful advancement for patients and potentially transformative for treatment."
Minimal Residual Disease Negativity
The belantamab mafodotin combination also showed statistically significant superiority on the key secondary endpoint of minimal residual disease (MRD) negativity (no detectable cancer cells) compared to the daratumumab combination. The rate of MRD negativity was 25.1% in the BVd group versus 10.4% in the DVd group (p<0.00001).
Safety and Tolerability
The safety and tolerability of the belantamab mafodotin regimen were consistent with the primary analysis and known safety profile of the individual agents. Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally manageable and resolvable with dose modification, and led to a low (10%) treatment discontinuation rate. Grade 3 or higher adverse events of clinical interest in the belantamab mafodotin combination and daratumumab combination arms, respectively included thrombocytopenia (56% versus 35%).
Blenrep's Journey
Blenrep received accelerated approval in 2020 as the first BCMA-targeting treatment. However, it was voluntarily withdrawn from the US market in 2022 after the DREAMM-3 trial failed to meet its primary endpoint. Despite this setback, GSK continued to explore Blenrep's potential in combination therapies.
Regulatory Filings and Future Prospects
Regulatory filings for Blenrep combinations have been submitted in several regions, including the EU, Japan, UK, Canada, Switzerland, and the US, based on the outcomes of the DREAMM-7 and DREAMM-8 trials. The FDA is expected to make a decision in July. GSK forecasts peak annual sales of $3.8 billion if the treatment is approved.
Competition and Market Landscape
Blenrep faces competition from other BCMA-targeting therapies, including CAR-T cell therapies like Abecma (Bristol Myers Squibb) and Carvykti (Johnson & Johnson), as well as bispecific antibodies such as Tecvayli (J&J) and Elrexfio (Pfizer). However, Blenrep offers a readily available, off-the-shelf treatment option, which could be advantageous in community settings where access to specialized technologies like CAR-T therapy is limited.
Ongoing Research
GSK is also exploring Blenrep in earlier lines of treatment and in combination with novel therapies. A Phase 1 test is ongoing in newly diagnosed patients to identify the dose and drug combination to evaluate in a pivotal study. The company is focused on improving the overall profile of the drug, maintaining efficacy while enhancing tolerability.
