Generic Name

Jelmyto

Mechanism

Jelmyto (belantamab mafodotin) is a targeted antibody‑drug conjugate (ADC) that couples a humanized anti‑BCMA monoclonal antibody to the cytotoxic payload monomethyl auristatin F (MMAF).
• BCMA Binding: The Fab fragment selectively binds B‑cell maturation antigen (BCMA), overexpressed on malignant plasma cells.
• Internalization & Catabolism: Upon binding, the complex is internalized and transported to lysosomes where the linker is cleaved.
• Cell‑death Induction: MMAF is released, disrupting microtubule dynamics, arresting the cell cycle in metaphase, and triggering apoptosis.
• Immunogenic Support: ADC’s Fc region may also mediate antibody‑dependent cellular cytotoxicity (ADCC) and complement activation, albeit secondary to the cytotoxic payload.

Pharmacokinetics

• Absorption/Distribution: Administered intravenously (IV); systemic exposure proportional to dose.
• Metabolism: Catabolism via proteolytic pathways; MMAF undergoes non‑enzymatic hydrolysis; free MMAF has high protein binding.
• Elimination: λ½ ≈ 7–9 days (depends on disease burden and renal function). Excreted mainly via protein catabolism, minimal renal clearance.
• Drug‑Drug Interactions: Low risk; no major CYP450 involvement. However, concomitant agents that influence renal function or ocular surface may affect toxicity profile.

Indications

• Relapsed/Refractory Multiple Myeloma (RRMM)
• Patients who have received ≥2 prior regimens, including a proteasome inhibitor and an immunomodulatory agent.
• Approved for use in adult patients with ≥6% bone marrow plasma cells or measurable disease.

Dosing

Special Instructions:
• Maintain strict pre‑infusion steroids and infusion duration to mitigate reactions.
• For patients requiring dose interruption, resume at 1 mg/kg after recovery.

Adverse Effects

Common (≥ 10 %)
• Keratopathy: corneal staining, decreased vision, dry eye.
• Thrombocytopenia (≥ 30 %).
• Neutropenia (≥ 10 %).
• Nausea, fatigue, alopecia.

Serious (≥ 1 %)
• Grade ≥ 3 ocular toxicity → vision loss.
• Severe neutropenia → febrile neutropenia.
• Thrombocytopenia → bleeding.
• Infusion reaction → anaphylaxis.

Management
• Keratopathy: Stop therapy, start preservative‑free artificial tears, consider topical steroids. Resume when Grade 1 or less.
• Cytopenias: Monitor CBC weekly; consider growth factors or dose delay.
• Infections: Prophylaxis with antivirals/antibiotics per institutional guidelines.

Monitoring

1. Ophthalmology
• Baseline slit‑lamp exam; repeat before each cycle and when symptoms arise.

2. Hematology
• CBC with differential at least weekly during first 2 cycles, then before each cycle.

3. Renal & Hepatic
• Serum creatinine, AST/ALT, bilirubin at baseline and per protocol.

4. Vitals & Infusion Tolerance
• Monitor blood pressure, heart rate, and patient comfort during infusion.

5. Patient Education
• Advise patients to report any change in vision, eye pain, or visual disturbances immediately.

Clinical Pearls

• Ocular toxicity is dose‑limiting; baseline ophthalmology is non‑negotiable.
• *Tip:* Use optical coherence tomography (OCT) to detect subtle corneal changes before visual symptoms appear.
• Steroid pre‑medication is essential; inadequate pre‑med can lead to severe infusion reactions that require emergent therapy.
• *Tip:* Combine H1/H2 blockers with dexamethasone to cover multiple reaction pathways.
• Keratopathy grading should drive dose modification, not just treatment cessation.
• *Tip:* Grade 2 can be mitigated with topical steroids; only Grade 3 warrants hold.
• Use a fixed‑dose weight bracket (e.g., ≤ 50 kg, 51–70 kg, > 70 kg) in busy clinics to simplify calculations while maintaining dosing accuracy.
• Thrombocytopenia can be more severe in heavily pre‑treated RRMM patients.
• *Tip:* Pre‑emptively consider low‑dose thrombopoietin receptor agonists if platelet count trend falls < 20 × 10⁹/L.
• Drug–drug interactions are minimal, but avoid concomitant use of strong CYP inhibitors of ocular surface metabolism (e.g., systemic fluoroquinolones) that may exacerbate keratopathy.
• Patient‑reported visual changes often precede objective grading; empower patients to record changes in a daily diary to trigger early intervention.

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• *This drug card summarizes evidence‑based information for healthcare professionals and medical students. For detailed prescribing information, refer to the official prescribing information and institutional treatment protocols.*