ASCO 2023: Comparing BLENREP (belantamab-mafodotin) to POMALYST (pomalidomide) and dex

This was a head-to-head comparison of two unique medicines used to treat relapsed/refractory multiple myeloma disease. Each year, more myeloma patients are living longer, higher quality lives than those the year before. This is due to the amazing medications that are being approved for relapsed/refractory myeloma patients. But which one is the best? That's the aim of researchers to discover. 

Watch Dr. Katja Weisel below as she describes this particular clinical trial and then read the summary: 

What question was the clinical trial trying to answer? What phase was this trial in?

Is belantamab mafadotin superior to pomalidomide and dexamethasone in comparison to each other when treating relapsed/refractory myeloma patients? 

This study evaluated BLENREP monotherapy (belantamab mafodotin, an antibody-drug conjugate that targets B-cell maturation antigen) against pomalidomide + low-dose dexamethasone (Pd) in adult patients with relapsed/refractory myeloma at second relapse or later (in their third line of therapy). 

This was a phase III (3) trial, meaning that it was a drug that had already proven safe and efficacious and was now being compared to a standard-of-care therapy that was previously approved. 

How many people participated and what were the qualifications? 

325 patients were enrolled into both the BLENREP (also referred to as belamaf) and POMALYST+ dex arms. The demographic and disease characteristics between the two arms were well balanced. 
The patients had to have relapsed/refractory disease to qualify for the trial. 

How long did the study last, and when was it completed? 

The clinical trial began in late 2019 and continued until September 2022. The patients each participated for about 15 months: they were exposed to the drug for approximately 4-5 months, and then they followed up for 10-11 months after exposure.

What were the final results? 

Interestingly, this trial did not meet its clinical endpoint of having a statistically significant progression-free survival (PFS) compared to pomalidomide + dex, and the drug belantamab-mafadotin (BLENREP) was taken off the market.

Although patients did receive around twelve months of progression-free survival on average with BLENREP, when compared to the Pd (pomalidomide/dex) arm, the hazard ratio was 1.03 and the Kappler-Meyer curve crossed over at ~4 months. There were earlier progressions on the monotherapy (BLRENREP aka belamaf) compared to the initial progressions on the doublet (pomalidomide and dexamethasone.) 

Investigators wonder if the longevity of the pomaylst + dex arm is due to the steroid, dexamethasone, itself, and therefore more investigation is needed.

Researchers believe longer followup will prove that those who haven't progressed while using BLENREP will remain in deep and durable remissions, outlasting those on the pomalidomide/dex arm. The majority of patients on BLENREP obtained a VGPR (very good partial response) to treatment or better.

No new safety signals were observed. BLENREP continues to be investigated in combination with established and novel agents in further clinical trials and results from those trials could bring a re-introduction of BLENREP to the U.S. drug market. 

Why is this important to patients in today's myeloma?

BLENREP, now unavailable in the current U.S. market, has to be further investigated. However, it has shown promising results in response to treatment for patients with multiple lines of therapy as responses tend to be long lasting and durable. BLENREP serves as a BCMA-targeting drug that needs less intervention than other drugs/treatments with similar targets such as CAR T-Cell Therapy and bispecific antibody therapies. BLENREP is certainly a treatment we need to keep our eye on in the near future. 

We thank the following investigators for their excellent work in making this trial possible, along with the myeloma patients and their caregivers who participated. 

Katja Weisel, Vania TM Hungria, Atanas Radinoff, Sosana Delimpasi, Gabor Mikala, Tamas Masszi, Jian Li, Marcelo Capra, Morio Matsumoto, Neal Sule, Mary Li, Astrid McKeown, Wei He, Shelley Bright, Brooke Currie, Julia Boyle, Joanna Opalinska, Meletios A. Dimopoulos