Brentuximab Vedotin — Drug Monograph

Brand names: Adcetris

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Anti-CD30 monoclonal antibody (cAC10) covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. After binding CD30 on tumor cells, the ADC is internalized, MMAE is released intracellularly, causes G2/M cell-cycle arrest and apoptosis. Bystander killing of CD30-negative cells in the tumor microenvironment also occurs.

FDA Indications

• Hodgkin lymphoma (HL) — after failure of autologous stem cell transplant (ASCT) or two prior multi-agent regimens (transplant ineligible)
• HL — post-ASCT consolidation (AETHERA) in patients at increased risk of relapse. Dose: 1.8 mg/kg (max 180 mg) IV q3w × 16 cycles, started 30–45 days after transplant. High-risk eligibility (≥1 required): primary refractory HL, relapse <12 months after front-line therapy, or extranodal disease at relapse. Trial data: 5-yr PFS 59% with BV vs. 41% with placebo (AETHERA, Moskowitz et al., Lancet 2015).
• HL — first-line with doxorubicin, vinblastine, dacarbazine (A+AVD, ECHELON-1)
• Systemic anaplastic large cell lymphoma (ALCL) — after failure of one prior therapy
• Primary cutaneous ALCL or CD30-expressing mycosis fungoides — after prior systemic therapy
• Peripheral T-cell lymphoma (PTCL) — first-line with CHP (A+CHP, ECHELON-2)

Common Side Effects

• Peripheral neuropathy (sensory and motor; dose-limiting; cumulative)
• Nausea
• Fatigue
• Neutropenia
• Diarrhea
• Infusion-related reactions

Clinical Pearl

Peripheral neuropathy is cumulative and often dose-limiting. The management algorithm: Grade 2 — delay dose, then resume at 1.2 mg/kg; Grade 3 — hold until ≤Grade 1, then reduce to 1.2 mg/kg; Grade 4 — discontinue. Most patients with treatment-related neuropathy improve after stopping, but improvement can be slow (months).

Related Therapies & Mechanisms

• Bendamustine (Treanda) — Lymphoma
• Doxorubicin (Adriamycin) — Lymphoma
• Etoposide (VePesid) — Lymphoma
• Pembrolizumab (Keytruda) — Lymphoma