Blenrep for Myeloma: Uses, Side Effects & Status

What Is Blenrep (belatanmab mafodotin) and How Does It Work?

Blenrep® (belantamab mafodotin (https://www.myeloma.org/blenrep-belantamab-mafodotin-blmf)) is a monoclonal antibody that targets B-cell maturation antigen (BCMA), a protein expressed on the surface of plasma cells, and releases a cytotoxic agent called Monomethyl auristatin F, which destroys the plasma cells. In addition, Blenrep has immunomodulatory properties.

This drug was initially approved as a single agent for patients with relapsed/refractory multiple myeloma who had been exposed to proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, as it addressed an unmet medical need in this population. However, it was withdrawn from the market because Blenrep did not demonstrate superiority over the combination of pomalidomide plus dexamethasone.

It’s important to note that the withdrawal of Blenrep does not imply that the drug is ineffective. In fact, it showed superiority over pomalidomide and dexamethasone, but the degree of superiority was not sufficient for continued approval.

The clinical development plan for Blenrep continued, incorporating key lessons learned from previous experience. Blenrep was combined with bortezomib and dexamethasone in a clinical trial involving patients with multiple myeloma in earlier lines of therapy, specifically after just one prior line of treatment. 

The DREAMM-7 and DREAMM-8 Clinical Trials

 The DREAMM-7 Trial (https://www.myeloma.org/videos/dreamm-7-belamafbvd-vs-dvd-rrmm-subgroup-analyses-phase-3-trial-comparing-regimens-after)used daratumumab, bortezomib, and dexamethasone as the control arm. A total of 494 patients were enrolled, with participants randomized to receive either belantamab mafodotin plus bortezomib and dexamethasone or daratumumab plus bortezomib and dexamethasone. The Blenrep-based combination demonstrated a greater depth of response, more durable responses, and significantly improved progression-free survival (PFS) compared to the control.

In the DREAMM-8 Trial (https://www.myeloma.org/videos/dreamm-8-study-belantamab-mafodotin-plus-pomalidomide-dexamethasone-shows-improved-outcomes), belantamab mafodotin was combined with pomalidomide and dexamethasone, in comparison with pomalidomide plus bortezomib and dexamethasone. This study was also conducted in relapsed and/or refractory myeloma patients after only one prior line of therapy. Similarly, the Blenrep-based combination outperformed the control in terms of response rate, durability of response, and progression-free survival.

The implications of the results from these two phase 3 randomized clinical trials are significant. Belantamab mafodotin, in combination with either bortezomib and dexamethasone or pomalidomide and dexamethasone, is poised to re-enter the treatment landscape for multiple myeloma. While regulatory approvals are still pending, they are anticipated given the superior outcomes demonstrated in the trials.

For patients with relapsed multiple myeloma after just one prior line of therapy, these results offer two novel treatment options that target BCMA, combined with well-known agents like bortezomib or pomalidomide. These combinations come with several notable advantages:

1. Off-the-shelf drugs that are readily available in all hospitals.
2. A simple administration of a 30-minute intravenous infusion without the need for premedication, step-up dosing, or hospitalization.
3. Flexible scheduling where treatment is administered every three or four weeks, with individual adjustments based on side effects, and it can be extended up to every eight weeks if needed.

Potential Side Effects of Blenrep (belantamab mafodotin)

Patients should be informed about potential side effects, with ocular toxicity (https://www.myeloma.org/managing-complications-side-effects/ocular-side-effects) being the most common Blenrep-related adverse event. The learning process from clinical trials has been important for managing this toxicity. Patients receiving Blenrep will be closely monitored for ocular symptoms such as blurred vision and dry eyes, as well as for changes in visual acuity. 

In the DREAMM trials, although approximately one-third of patients experienced some degree of visual acuity worsening, it was moderate in most cases. Importantly, this side effect was generally reversible with appropriate management, including treatment holds, dose reductions, and administering the drug less frequently. The use of artificial tiers as well as cooling eyes mask during the administration of Blenrep can help mitigate the ocular toxicity.

The Future of Blenrep in Myeloma Treatment

To summarize, it is highly likely that Blenrep will soon be included as a treatment option for myeloma patients with relapsed/refractory disease after at least one prior line of therapy. Other therapies that redirect T-cells and target BCMA may also become available, and disease- and patient-specific characteristics will be crucial in selecting the most appropriate option. Having multiple choices will enable doctors to individualize treatment, optimizing outcomes for each patient.

About Maria V. Mateos, MD, PhD