OncoPharm Tale from the Crypt: Belantamab Mafodotin
Oct 30, 2025
This Halloween, the spotlight is on belantamab mafodotin, a drug with a tumultuous journey. After its initial 2020 approval, it faced withdrawal due to poor performance in trials. However, it made a strong comeback in DREAM7, outshining daratumumab in effectiveness. Key discussions include ocular toxicity concerns, innovative monitoring strategies, and potential real-world applications. Listeners will be intrigued by the future implications and research opportunities surrounding this intriguing therapy.
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Drug Mechanism And Early Approval
- Belantamab mafodotin is a BCMA-targeting antibody–drug conjugate carrying a microtubule toxin payload.
- It received accelerated approval in 2020 for relapsed/refractory multiple myeloma based on response rates.
DREAM3's Surprising Negative Result
- DREAM3 tested belantamab mafodotin as monotherapy versus pomalidomide+dexamethasone in ≥3rd-line patients.
- The trial showed crossing Kaplan–Meier curves, no OS advantage, and puzzling PFS hazard ratio results.
Crossing Curves Reflect Tolerability Effects
- DREAM3 curves crossed: early harms then long-term benefit among tolerant patients.
- Toxicity interruptions likely caused early progression in some patients, skewing results.