Generic Name

Arikayce

Mechanism

• Target engagement:
• *Belantamab mafodotin* is a monoclonal antibody that binds BCMA expressed on malignant plasma cells, mediating internalization.
• Drug delivery:
• The antibody is linked to monomethyl auristatin F (MMAF), a potent microtubule inhibitor.
• Cytotoxic effect:
• Inside the cell, MMAF disrupts microtubule dynamics, inducing cell cycle arrest and apoptosis of BCMA‑positive myeloma cells.
• Immunogenic effect:
• Because the antibody retains Fc‑R engagement, antibody‑dependent cellular cytotoxicity (ADCC) may contribute modestly, but the primary kill mode is ADC‑mediated.

Pharmacokinetics

Indications

• Relapsed or refractory multiple myeloma in adults, after ≥ 2 prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug, and anti‑CD38 antibody.
• Approved for use as monotherapy (≤ 4 prior regimens) and in combination with low‑dose cyclophosphamide in certain subjects with limited options.

Contraindications

• Contraindications
• Known hypersensitivity to belantamab mafodotin or any excipient.
• Warnings
• Serious ocular toxicity (keratopathy): baseline and periodic ophthalmologic assessment required.
• Peripheral neuropathy – may be exacerbated in patients with pre‑existing neuropathy.
• Cytopenias (neutropenia, thrombocytopenia) – risk of infection and bleeding.
• Anemia – may worsen pre‑existing anemia.
• Precautions
• Not recommended for patients with severe renal or hepatic impairment pending further data.
• Avoid simultaneous use of drugs that may induce significant ocular side effects (e.g., certain anti‑VEGF agents).

Dosing

• Standard regimen:
• 3.4 mg/kg IV every 3 weeks (Q3W).
• Alternating with cytotoxic matching if in combination with low‑dose cyclophosphamide.
• Infusion details:
• 4‑hour infusion; pre‑medication with antihistamine or corticosteroid is not routinely required unless infusion reactions observed.
• Dose modifications:
• Hold for Grade ≥ 2 keratopathy; resume when resolved to Grade 0–1.
• Delays or reductions for Grade ≥ 3 hematologic toxicity.
• Treatment duration:
• Continue until disease progression or intolerable toxicity.

Adverse Effects

• Serious adverse events:
• Ocular: Acute vision loss, corneal ulceration.
• Infections: Febrile neutropenia, especially in neutropenic patients.
• Hepatotoxicity: Rare elevations in ALT/AST > 5× ULN.
• Monitoring for ocular toxicity:
• Best corrected visual acuity (BCVA), slit‑lamp exam, corneal grading (UNC 2020 criteria).

Monitoring

• Baseline
• Complete blood count (CBC) with differential; comprehensive metabolic panel (CMP).
• Ophthalmologic exam (visual acuity, slit‑lamp).
• During therapy
• CBC pre‑infusion and 2–3 days post‑dose.
• Ophthalmologic assessment every 2–3 cycles or sooner if symptomatic.
• Monitor for signs of infection, especially febrile neutropenia.
• Dose adjustments
• Hold or reduce dose for Grade ≥ 2 keratopathy or Grade ≥ 3 cytopenias.

Clinical Pearls

• Ocular vigilance is paramount:
• A patient with pre‑existing dry eye or ocular surface disease warrants a baseline comprehensive exam and a more frequent follow‑up schedule.
• Schedule flexibility for infusion timing:
• Ocular toxicity peaks around 2–3 weeks post‑dose; if keratopathy appears before the next infusion, consider delaying the next dose to allow recovery.
• Hematologic support:
• Granulocyte‑stimulating factors (G‑CSF) can be employed proactively for patients with a prior history of neutropenia to reduce dose reductions.
• Drug–drug interactions:
• No direct CYP450 interactions; however, concomitant use of ocular medicines that may induce corneal toxicity (e.g., topical NSAIDs) should be avoided.
• Patient counseling:
• Emphasize the importance of reporting any new or worsening vision changes, eye pain, or blurred vision promptly.
• Adjunctive GI prophylaxis:
• Antiemetics (e.g., ondansetron) before infusion can reduce nausea, improving adherence.

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• Arikayce offers a novel, BCMA‑directed ADC option for patients with limited salvage therapy options but requires diligent ocular and hematologic monitoring to mitigate its unique iodine‑associated, high‑grade keratopathy and cytopenias.