On Tuesday, February 6th, at the American Society of Clinical Oncology (ASCO) Plenary Series, promising news of the myeloma treatment belantamab mafodotin, commercially known as BLENREP or Blenrep, was released. 

The DREAMM-7 phase III trial shows a Blenrep combination nearly tripled median progression-free survival versus standard of care combination in patients with relapsed/refractory multiple myeloma. In this trial, Blenrep was combined with bortezomib (Velcade) and dexamethasone and was compared against a triple combination of daratumumab, bortezomib, and dexamethasone in second-line or later lines of myeloma therapy. 

What is belantamab mafadotin? 

Belantamab mafadotin is an antibody-drug conjugate that was previously used for relapsed/refractory myeloma patients before being taken off the market in November of 2022. Its commercial name is BLENREP, or Blenrep. 

Blenrep targets a protein on the surface of myeloma cells called BCMA, and was the first FDA-approved therapies in multiple myeloma to do so. Today, we have a number of therapies targeting BCMA, including bispecific antibodies like elranatamab and teclistimab, and CAR-T products like Abecma and CARVYKTI. 

If you would like to learn more about belantamab mafadotin (Blenrep), you can watch this 15-minute HealthTree University Video in which myeloma specialists explain the mechanism, side effects, and importance of this treatment: Know Your Myeloma Therapy: BLENREP. 
 

Results of the DREAMM-7 Phase III Clinical Trial 

The primary endpoint for this trial, progression-free survival, was met and proven to be superior to the Dara-BorDex combination that it was compared against. 

For context, the primary endpoint of a cancer clinical trial is what determines whether or not a trial was successful or unsuccessful. It is the data point that is measured at the end of the trial, as the main result, to see if a given treatment worked. 

Progression-free survival is usually indicated as the time from which the treatment began for an individual patient to the time that they are showing clinical signs of relapse/disease progression. 

In this trial, researchers measured the progression-free survival of patients on both the Blenrep-bortezomib-dexamethasone combination and the daratumumab-bortezomib-dexamethasone combination and compared the two. 

• The Blenrep combination showed a 59% reduction in the risk of disease progression or death when compared to the daratumumab combination. 
• With a median follow-up of 28.2 months, the median progression-free survival (PFS) was 36.6 months with the Blenrep combination compared to the 13.4 months PFS of the daratumumab combination. 
• Notably, the progression-free survival benefit was observed across all prespecified subgroups of patients within the trial, including those with high-risk cytogenetics and those who were refractory to lenalidomide (REVLIMID). 
• The safety and tolerability profile of the Blenrep combination was consistent with the known profile of the individual agents- meaning, there were no unexpected or novel side effects due to the combination of these therapies. 

Other secondary endpoints were measured and can be seen in the table below shared by GSK. 

Why was Blenrep taken off the market by the FDA? 

For a clinical trial designed to take a drug to full or accelerated approval for the FDA, the FDA bases its approval decision on whether or not said trial met its primary endpoint. 

BLENREP (belantamab mafodotin) was granted accelerated approval in August 2020 by the FDA for relapsed/refractory patients who had received at least four prior treatments including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug. 

The accelerated approval was granted by the FDA based on the DREAMM-2 overall response rate (ORR) study results. The early approval was contingent on GSK's DREAMM-3 Phase III study confirming primary endpoint benefit confirmation. 

On November 7, 2022, interim results of the DREAMM-3 study were reported. In the DREAMM-3 study, BLENREP alone was compared to the dual pomalidomide/dex combination. In the follow-up at around 11 months into the study, progression-free survival (PFS) was longer in the BLENREP group (11.2 months) compared to the pom/dex group (7 months). However, the PFS hazard ratio comparing the two treatments was 1.03 (if the hazard ratio is 1, it shows no difference between the two treatment arms). 

So, while the drug still performed well, it did not meet its primary endpoint of statically significant progression-free survival, which is why it was taken off the market for the time being. 

Since November 2022, GSK has continued to produce several trials like DREAMM-7 that show Blenrep as being statically significant when reaching its endpoint, and researchers, physicians, and myeloma patients and caregivers are hopeful these efficient results indicate a future FDA approval (or reinstatement) of Blenrep in myeloma treatment. 

For more information on why this drug was taken off the market, you can read the article here: What GSK's BLENREP Change Means for US Myeloma Patients (Nov 22)

Why could Blenrep be an important addition to myeloma treatment options for relapsed/refractory myeloma patients? 

A reinstatement of belantamab mafadotin as a FDA-approved myeloma therapy would be important to the myeloma community for the following reasons (and more!): 

1. It already existed as a treatment for relapsed/refractory myeloma patients and was found efficacious in fighting myeloma. 
2. It targets BCMA, which is a prevalent myeloma target, and while it has ocular toxicity side effects, these can be easily managed. Its side-effect profile does not include the risk of serious infections at the same level as other BCMA-targeting therapies, such as bispecific antibodies. 
3. It can be used as a bridging therapy for patients who are waiting to get their reengineered T-cells back before CAR-T. 
4. It can be a useful option for older or more frail patients who are not candiates for novel immunotherapies or other combinations. 
5. It's simply always better for both the patient and the physician to have more treatment options available to them, as we are always looking for more options to improve the overall survival and quality of life of people with myeloma. 

Conclusion 

The DREAMM-7 clinical trial results are promising, and exciting news for those who are watching for a possible reapproval of BLENREP into the U.S. drug market. We look forward to more data being shared and more news regarding this BCMA-targeting antibody drug conjugate.