Chemical Identity

Property	Value
Molecular Weight	~153 kDa (ADC)
Peptide Payload	Monomethyl auristatin E (MMAE)
Linker	Valine-citrulline (protease-cleavable)
DAR	~4
Target	CD30

Structure

Brentuximab vedotin (Adcetris) is a chimeric anti-CD30 IgG1 monoclonal antibody conjugated to 4 molecules of MMAE via a valine-citrulline dipeptide linker. The linker is stable in plasma but cleaved by lysosomal cathepsins after receptor-mediated endocytosis.

Mechanism of Action

The antibody binds CD30 on Hodgkin Reed-Sternberg cells and ALCL cells, triggering internalization. After lysosomal cleavage of the Val-Cit linker, released MMAE disrupts microtubule networks, causing cell cycle arrest and apoptosis. Bystander effect kills neighboring CD30-negative cells.

Clinical Applications

• Classical Hodgkin lymphoma: After autologous stem cell transplant failure, or frontline with AVD
• Anaplastic large cell lymphoma: Systemic ALCL after prior chemotherapy
• Cutaneous T-cell lymphoma: CD30-expressing mycosis fungoides
• CD30-expressing lymphomas: Various subtypes

Pharmacokinetics

• Half-life: 4-6 days (ADC), 3-4 days (MMAE)
• Steady state: ~21 days
• Cmax (MMAE): ~5 ng/mL
• Metabolism: MMAE by CYP3A4
• Route: IV infusion every 3 weeks (1.8 mg/kg)

Safety and Side Effects

Peripheral neuropathy (dose-limiting, cumulative), neutropenia, thrombocytopenia, anemia, fatigue, nausea, diarrhea, and rare progressive multifocal leukoencephalopathy (JC virus). Stevens-Johnson syndrome reported rarely.

References

• Younes, A., et al. (2010). Brentuximab vedotin for relapsed Hodgkin lymphoma. New England Journal of Medicine, 363, 1812-1821.
• Connors, J.M., et al. (2018). ECHELON-1: brentuximab vedotin with AVD for Hodgkin lymphoma. New England Journal of Medicine, 378, 331-344.