- Class: Antibody–drug conjugate (ADC) – anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE)
- Type: IV targeted therapy.
Mechanism of Action (MOA)
- CD30 targeting: Brentuximab binds CD30 receptors on malignant cells (e.g., Hodgkin lymphoma, anaplastic large cell lymphoma).
- Internalization: The ADC is internalized into the cell.
- Cytotoxic release: MMAE is released → disrupts microtubules → cell cycle arrest and apoptosis.
- Provides targeted delivery of chemotherapy, sparing most normal cells.
Clinical Uses
- Hodgkin lymphoma: relapsed/refractory after autologous stem cell transplant or ineligible patients.
- Systemic anaplastic large cell lymphoma (sALCL): relapsed/refractory disease.
- Investigational use: other CD30-positive lymphomas, combination regimens.
Dosing (Adults)
- 1.8 mg/kg IV every 3 weeks (up to 16 cycles).
- Administer over 30 minutes; premedication not routinely required.
- Dose adjustments for:
- Hepatic impairment (reduce in moderate/severe).
- Renal impairment (caution in CrCl <30 mL/min).
- Hematologic toxicity.
Toxicities
- Hematologic: neutropenia, anemia, thrombocytopenia.
- Peripheral neuropathy – cumulative, dose-limiting (MMAE-related).
- Fatigue, nausea, diarrhea.
- Infusion-related reactions – rare but possible.
- Rare: hepatotoxicity, progressive multifocal leukoencephalopathy (PML).
Monitoring
- CBC prior to each cycle.
- Neurologic assessment for peripheral neuropathy.
- Liver function tests.
- Observe for infusion reactions during and after infusion.
- Renal function in patients with pre-existing impairment.
Summary
Brentuximab (Adcetris®) is an anti-CD30 ADC delivering MMAE to lymphoma cells. Key concerns are peripheral neuropathy, myelosuppression, and infusion reactions, requiring monitoring of CBC, liver function, and neurologic status.