Jadenu
Jadenu
Generic Name
Jadenu
Mechanism
- Target: B‑cell maturation antigen (BCMA) highly expressed on malignant plasma cells.
- Selective Binding: The humanized IgG1 antibody portion binds BCMA with high affinity.
- Internalization & Release: Post‑binding, the ADC is endocytosed; cathepsin‑cleavable linker releases monomethyl auristatin F (MMAF).
- Cytotoxic Effect: MMAF microtubule‑disrupting agent arrests cell division at the G₂/M checkpoint, leading to apoptotic cell death.
Pharmacokinetics
| Parameter | Key Points |
| Absorption | Intravenous infusion (no oral availability). |
| Distribution | Highly protein‑bound (~95 %); tissue penetration limited by large molecular size. |
| Metabolism | Predominantly proteolytic catabolism of the antibody and linker cleavage; MMAF metabolized via hepatic β‑oxidation and glucuronidation. |
| Elimination | ~60 % renal excretion (mostly unchanged antibody fragments); ~40 % fecal via biliary excretion. |
| Half‑life | Approx. 14–16 days (steady‑state reached after 2–3 cycles). |
| Drug–Drug Interactions | Minimal CYP450 interactions; caution with other cytotoxic agents that affect bone marrow reserve. |
Indications
- Relapsed/refractory multiple myeloma after ≥ 4 prior lines (PI + IMiD + CD‑38).
- Approved in the USA; ongoing studies evaluate earlier lines and combination regimens (e.g., with pomalidomide or daratumumab).
Contraindications
- Confirmed hypersensitivity to belantamab‑mafodotin or any excipient.
- Severe ocular disease (e.g., pre‑existing corneal ectasia).
- Active uncontrolled infections or significant organ dysfunction.
- Warning: Ocular toxicity (keratopathy), cytopenias, infusion‑related reactions, and rare tumor lysis syndrome.
Dosing
- Initial dose: 2.5 mg/kg IV over 60 minutes on Day 1 of each 21‑day cycle.
- Pre‑infusion meds: Antihistamine and acetaminophen at least 30 min before to mitigate infusion reactions.
- Infusion adjustments:
- Grade ≥ 2 keratopathy → 2‑week hold, then resume at 2.0 mg/kg.
- Grade 3–4 keratopathy → repeat dose‑reduction strategy or discontinuation.
- Duration: Continue until disease progression, unacceptable toxicity, or patient withdrawal.
Adverse Effects
- Common (≥ 10 %):
- Ocular: blurred vision, photophobia, corneal epithelial micro‑defects.
- Myelosuppression: neutropenia, anemia, thrombocytopenia.
- Infusion reactions: chills, mild rash.
- Serious (≥ 1 %):
- Keratopathy grade 3–4 (potential loss of vision).
- Tumor lysis syndrome (rare).
- Severe cytopenias leading to infection or bleeding.
- Opportunistic infections (viral, fungal).
Monitoring
- Baseline ophthalmology exam (visual acuity, slit‑lamp).
- Ophthalmologic re‑assessment at each cycle start or sooner if visual changes.
- CBC, CMP: baseline, weekly during cycles 1–2, then per cycle.
- Bone‑marrow evaluation if cytopenias ≥ Grade 3.
- Infusion‑related monitoring: vitals during and post‑infusion.
Clinical Pearls
- Early Keratopathy Detection: Screen patients for contact lens use and screen for pre‑existing corneal conditions; prompt referral to ophthalmology can prevent irreversible vision loss.
- Dose‑Adaptation Algorithm: A two‑step reduction (2.5 → 2.0 → 1.5 mg/kg) often restores ocular tolerability while maintaining efficacy.
- Combination Potential: Studies combining Jadenu with lenalidomide/pomalidomide show synergy; however, overlapping myelotoxicity necessitates close CBC monitoring and possible dose adjustments.
- Adjuvant Eye Drops: Artificial tears and preservative‑free lubricants may mitigate minor ocular symptoms; avoid topical NSAIDs post‑infusion to prevent further epithelial damage.
- Drug‑Administration Window: Administer at the beginning of the day; prolonging infusion beyond 60 min has not shown benefit and may increase infusion‑related reactions.
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• References (abridged):
1. *Belantamab mafodotin—FDA prescribing information.*
2. J. Varga et al., *J Clin Oncol*, 2021.
3. B. P. Smith et al., *Blood*, 2022.
*(All data as of January 2026.)*