Belantamab mafodotin, known as Blenrep, is a medication for multiple myeloma, a type of blood cancer. It represents a targeted therapy approach, focusing on specific characteristics of cancer cells to deliver treatment more precisely. It was initially used for patients whose myeloma had become difficult to manage with other available treatments.
How Belantamab Mafodotin Works
Belantamab mafodotin is an antibody-drug conjugate (ADC), a “guided missile” designed to target and destroy cancer cells. This compound consists of two primary components: an antibody and a cytotoxic agent. The antibody, belantamab, acts as the guiding part, binding to a protein called B-cell maturation antigen (BCMA) on multiple myeloma cells.
Once the belantamab antibody attaches to the BCMA protein on a myeloma cell, the ADC is internalized into the cell. Inside the cancer cell, the cytotoxic agent, mafodotin, is released from the antibody. Mafodotin disrupts the cell’s internal structure, specifically interfering with microtubules essential for cell division and survival. This disruption leads to the death of the myeloma cell, while minimizing harm to healthy cells that do not express BCMA.
Patient Eligibility
Belantamab mafodotin was intended for adult patients with “relapsed” or “refractory” multiple myeloma. Relapsed multiple myeloma means the cancer has returned after a period of improvement following initial treatment. Refractory multiple myeloma indicates that the cancer has not responded to treatment or has progressed within 60 days of the last therapy.
Initial approval focused on patients who had undergone extensive prior treatments. These individuals had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. This positioned it as a later-line treatment option for patients with limited choices.
Administration and Monitoring
Belantamab mafodotin is given intravenously, usually in a clinical setting such as a hospital or infusion center. The infusion takes about 30 minutes. It is typically given once every three weeks until disease progresses or unacceptable side effects occur.
A significant aspect of receiving this treatment involves regular and thorough eye examinations. These ophthalmic evaluations monitor for potential eye-related side effects. Patients need an eye exam within three weeks before starting treatment, then within two weeks prior to each subsequent dose. This frequent monitoring helps detect and manage ocular changes early.
Potential Side Effects
One common side effect of belantamab mafodotin is ocular toxicity, affecting the eyes. This manifests as keratopathy, or changes in the cornea, the clear outer layer at the front of the eye. Symptoms of keratopathy can include blurred vision, dry eyes, light sensitivity (photophobia), and general eye irritation or pain.
These corneal changes often present as microcyst-like epithelial changes (MECs) visible during a slit lamp eye examination, sometimes without noticeable symptoms. While many ocular events are mild, they frequently lead to dose adjustments or delays in treatment. Patients may also experience decreased visual acuity, with some cases involving severe vision loss or corneal ulcers.
Beyond ocular issues, other common side effects include blood count abnormalities. These can involve thrombocytopenia (low platelet counts) and anemia (low red blood cells). Patients may also experience gastrointestinal symptoms like nausea, constipation, or diarrhea, and fatigue.
Regulatory and Market Status
Belantamab mafodotin received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2020 for relapsed or refractory multiple myeloma. This approval was contingent on further verification of its clinical benefit through confirmatory trials. It was initially available as a monotherapy for patients who had received at least four prior lines of therapy.
However, the manufacturer began withdrawing belantamab mafodotin from the U.S. market in November 2022, at the FDA’s request. This decision followed the results of the DREAMM-3 confirmatory phase 3 trial, which compared belantamab mafodotin monotherapy to a standard treatment of pomalidomide plus low-dose dexamethasone. The trial did not meet its primary goal of superior progression-free survival, a requirement for continued accelerated approval.
Despite U.S. market withdrawal, belantamab mafodotin may still be available through compassionate use programs or in other countries where it remains approved, such as the UK and Japan. Ongoing clinical trials, such as DREAMM-7 and DREAMM-8, are evaluating belantamab mafodotin in combination with other therapies, which could influence its future regulatory status.