Where Does Blenrep Fit in Multiple Myeloma Treatment Paradigm for Relapse? Excitement Over 48% Reduction in Disease Progression

In August 2020, the FDA granted accelerated approval for Blenrep to treat relapsed/refractory multiple myeloma patients who had received at least four prior treatments, including an anti-CD38 monoclonal antibody, an immunomodulatory drug, and a proteasome inhibitor. However, in November 2022, the interim analysis of the DREAMM-3 clinical trial revealed that the new therapy did not achieve its primary endpoint of statistically significant progression-free survival, leading to its temporary removal from the market.

Despite this setback, the pharmaceutical company, Glaxo-Smith Kline (GSK), kept studying the drug to get it back on the market, and more promising data was published this year, marking a significant milestone.

During the American Society of Clinical Oncology (ASCO)’s 2024 meeting, positive results were shared from an interim analysis of the DREAMM-8 study evaluating Blenrep in combination with pomalidomide plus dexamethasone (PomDex), versus the standard of care, bortezomib plus PomDex.

What Did the Data Show?

The DREAMM-8 phase III clinical trial is a multicentre, open-label, randomized trial evaluating the efficacy and safety of the Blenrep combination versus the standard of care combination in relapsed or refractory multiple myeloma. This study included patients previously treated with at least one prior line of multiple myeloma therapy, comprising 302 participants at 95 sites in 18 countries.

This late-breaking data reported a significant and valuable improvement in the primary endpoint of progression-free survival (PFS) (Hazard ratio: 0.52 [95% confidence interval (CI): 0.37-0.73], p-value < 0.001), translating into a 48% reduction of disease progression or death.

Additionally, at the end of one year, 71% (95% CI: 63-78) of patients in the Blenrep combination group compared to 51% (95% CI: 42-60) in the bortezomib combination group were alive and had not progressed. A benefit for Blenrep combination was seen in all predefined subgroups, including those with unfavorable prognostic factors, such as patients resistant to lenalidomide and those with high-risk cytogenetics.

Among treatment responders, the median response duration was 17.5 months with standard care, whereas with Blenrep, the median duration had not yet been reached.

The therapy was prescribed as follows:

• Blenrep at 2.5 mg/kg intravenously in cycle 1, then 1.9 mg/kg every 4 weeks starting on cycle 2, pomalidomide at 4 mg orally on days 1 to 21, and dexamethasone at 40 mg on days 1, 8, 15, and 22.
• Patients in the comparator arm received bortezomib at 1.3 mg/m2 subcutaneously on days 1, 4, 8, and 11 of cycles 1 to 8, followed by days 1 and 8 of each subsequent cycle; pomalidomide at 4 mg orally on days 1 to 14; and dexamethasone at 20 mg on the day of, and after bortezomib.

Along with the results of this study, there were additional positive results from DREAMM-7 trial, which were reported earlier this year.

“Taken together with the results of DREAMM-7, these data highlight the potential of belamaf-containing triplets to address an unmet need of novel regimens to treat patients with myeloma for first relapse,” Suzanne Trudel, MD, of the Princess Margaret Cancer Center in Toronto, explained.

With these two positive trials, GSK intends to submit Blenrep for FDA approval in the second half of this year, according to Hesham Abdullah, M.D., GSK’s head of oncology R&D.

Notably, in a previous conversation with SurvivorNet, hematologist/oncologist Dr. Sumit Madan explained that therapies doctors have to treat relapsed multiple myeloma, including Blenrep, tend to be well-tolerated.

“Fortunately, the treatments that we have for multiple myeloma are overall very well tolerated,” Dr. Madan explained. “When we give a treatment to our patients, we make sure that they will be able to tolerate those drugs.”

The Future for Blenrep in Multiple Myeloma

The results from the DREAMM-7 and DREAMM-8 clinical trials are anticipated to drive the reapproval of Blenrep as an FDA-approved therapy for relapsed/refractory myeloma patients. This reapproval would be crucial for the myeloma community for several reasons:

1. The potential for a BCMA-targeted treatment option, offering broad patient eligibility and an in-office infusion process within a community oncology treatment center, could significantly enhance the patient experience.
2. Blenrep’s benefits were observed even in patients with poor prognosis due to a failure to respond to lenalidomide or with certain high-risk cellular features.
3. The concern regarding toxicity is still present, however, management of eye-related side effects has improved.

What to Expect Next

The European Medicines Agency (EMA) has accepted GSK’s marketing authorization application (MAA) for Blenrep (belantamab mafodotin) in combination with either bortezomib plus dexamethasone (BorDex) or pomalidomide plus dexamethasone (PomDex) for the treatment of relapsed or refractory multiple myeloma (RRMM).

According to a company press release on July 19, 2024, EMA’s Committee for Medicinal Products for Human Use will soon begin its formal review of the MAA to make a recommendation to the European Commission.

The journey of Blenrep from market withdrawal to a beacon of hope for patients highlights the importance of persistent research and innovation. What once seemed like a failed endeavor has now transformed into a potential breakthrough, offering new hope for those in need.

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