Blenrep (Belantamab Mafodotin-blmf): Complete Drug Profile
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- What Is Blenrep?
- How Does Blenrep Work?
- FDA Approval and Regulatory Status
- Indications and Usage
- Dosage and Administration
- Formulation and Composition
- Efficacy: Clinical Trial Data
- Side Effects and Warnings
- Special Monitoring Required
- Who Should Not Use Blenrep?
- Can You Still Access Blenrep in the US?
- Are There Alternatives or Competitors?
- Summary Table
- Storage and Handling
What Is Blenrep?
Blenrep is the brand name for belantamab mafodotin-blmf, a monoclonal antibody–drug conjugate (ADC) used in the treatment of relapsed or refractory multiple myeloma (RRMM). It targets BCMA (B-cell maturation antigen), a protein found almost exclusively on the surface of malignant plasma cells, and delivers a potent cytotoxic agent directly into those cells.
It belongs to a class of antibody-drug conjugates that combine the specificity of antibodies with the cell-killing ability of chemotherapy.
How Does Blenrep Work?
Blenrep binds to BCMA, which is highly expressed on malignant plasma cells in multiple myeloma. Once attached:
- The ADC-antibody binds to BCMA on the cancer cell surface.
- It is internalized by the cell.
- Inside, it releases mafodotin, a cytotoxic microtubule inhibitor.
- This disrupts cell division, leading to cell death.
FDA Approval and Regulatory Status
| Event | Date | Notes |
|---|---|---|
| Accelerated Approval | August 5, 2020 | Approved by the FDA under Accelerated Approval Pathway for RRMM patients after ≥4 prior lines of therapy |
| European Approval | August 25, 2020 | Approved by EMA for similar use |
| Withdrawal from Market | November 22, 2022 | GSK voluntarily withdrew US marketing authorization after confirmatory Phase 3 trial DREAMM-3 failed to meet progression-free survival (PFS) endpoints |
| Current Access | USA: Discontinued commercially, may be available via clinical trials or compassionate use; EU: Limited access depending on country and hospital policies |
Indications and Usage
Blenrep was indicated for:
Adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies, including:
- An anti-CD38 monoclonal antibody,
- A proteasome inhibitor,
- An immunomodulatory agent.
It was considered an option when standard therapies had failed.
Dosage and Administration
| Parameter | Detail |
|---|---|
| Dosage | 2.5 mg/kg |
| Route | Intravenous (IV) infusion |
| Frequency | Once every 3 weeks (Q3W) |
| Duration | Until disease progression or unacceptable toxicity |
| Infusion Time | Over ~30 minutes (no premedication usually required) |
Formulation and Composition
| Component | Description |
|---|---|
| Active Substance | Belantamab mafodotin-blmf |
| Drug Class | BCMA-targeted antibody-drug conjugate |
| Cytotoxic Payload | Mafodotin (auristatin derivative) |
| Form | Lyophilized powder in single-dose vial |
| Reconstitution | Requires dilution and preparation under sterile conditions by a healthcare professional |
Efficacy: Clinical Trial Data
DREAMM-2 Trial (Phase II)
The pivotal trial for accelerated approval.
- Population: 196 heavily pretreated patients (median 7 prior therapies)
- Response Rate: ~32% achieved overall response (partial or better)
- Median Duration of Response: 11 months
- Median PFS: ~2.9 months
- Median OS: ~13.7 months
- Notable Adverse Event: High incidence of keratopathy (corneal damage)
DREAMM-3 Trial (Phase III)
Compared Blenrep monotherapy vs. pomalidomide + dexamethasone.
- Result: Did not meet primary endpoint (PFS superiority)
- Consequence: Approval withdrawn in US (2022)
Side Effects and Warnings
Common Side Effects (>20%):
| Side Effect | Incidence |
|---|---|
| Keratopathy (eye toxicity) | ~70% |
| Blurred vision | ~30–40% |
| Dry eyes / Eye pain | ~25% |
| Fatigue | ~30% |
| Nausea | ~25% |
| Thrombocytopenia | ~20% |
Ophthalmic exams were required before each dose, due to the high risk of corneal toxicity.
Serious Side Effects:
- Severe keratopathy (leading to treatment delay/discontinuation)
- Thrombocytopenia
- Infusion-related reactions
- Risk of infection due to immunosuppression
Special Monitoring Required
| Before Treatment | During Treatment |
|---|---|
| Baseline eye exam | Eye exam before each dose |
| Blood counts (CBC) | Monitor platelets and neutrophils |
| Liver function | Periodic LFTs |
| Pregnancy test (if applicable) | Not safe in pregnancy; use effective contraception |
Who Should Not Use Blenrep?
Contraindicated or not recommended in:
- Pregnant or breastfeeding women
- Patients with active ocular disease not monitored closely
- Hypersensitivity to any ADC component
Can You Still Access Blenrep in the US?
Currently NOT available through regular pharmacy channels.
After its market withdrawal, access may be limited to:
- Clinical trials
- Expanded access programs (compassionate use) coordinated by GSK
Are There Alternatives or Competitors?
Yes. Other BCMA-targeted therapies and agents approved for RRMM include:
| Drug | Target | Type | Notes |
|---|---|---|---|
| Carvykti (ciltacabtagene autoleucel) | BCMA | CAR-T | One-time infusion; high response rate |
| Abecma (idecabtagene vicleucel) | BCMA | CAR-T | Requires manufacturing time |
| Tecvayli (teclistamab) | BCMA | Bispecific antibody | Off-the-shelf, SC injection |
| Elrexfio (elranatamab) | BCMA | Bispecific antibody | Newer approval, similar mechanism |
These alternatives offer more durable response rates, but may involve different risk profiles and logistics (CAR-T = custom cell therapy; bispecifics = continuous dosing).
Summary Table
| Feature | Blenrep Details |
|---|---|
| Generic Name | Belantamab mafodotin-blmf |
| Brand Name | Blenrep |
| Approval Status (US) | Withdrawn (2022) |
| Drug Class | ADC (Anti-BCMA) |
| Administration | IV infusion, every 3 weeks |
| Main Indication | Relapsed/Refractory Multiple Myeloma |
| Most Notable Risk | Eye toxicity (keratopathy) |
| Access (2025) | Clinical trial or expanded use only |
| Alternative Therapies | CAR-T (Abecma, Carvykti), bispecifics (Tecvayli, Elrexfio) |
Storage and Handling
- Store unreconstituted vials refrigerated (2–8°C)
- Protect from light
- Reconstituted solution should be used within 6 hours
- Handled and administered by trained oncology professionals
Blenrep represented a promising and innovative approach to treating RRMM, particularly due to its off-the-shelf accessibility compared to CAR-T options. However, its ocular toxicity and underperformance in Phase III trials led to a market withdrawal, emphasizing the importance of long-term efficacy and safety validation.
Patients may still access it through clinical trials or compassionate programs, while newer BCMA therapies (Tecvayli, Elrexfio, Abecma, Carvykti) continue to shape the future of multiple myeloma care.
