Brentuximab vedotin

Summary

Brentuximab vedotin (Adcetris) is an antibody-drug conjugate approved for CD30-positive hematologic malignancies including classical Hodgkin lymphoma and systemic anaplastic large cell lymphoma. It combines targeted CD30 binding with the potent antimitotic payload MMAE to selectively kill tumor cells.

Mechanism of Action

Targets CD30-expressing tumor cells; the anti-CD30 antibody binds CD30, the conjugate is internalized, and the linker is cleaved by lysosomal proteases releasing MMAE, which disrupts microtubule polymerization leading to G2/M cell cycle arrest and apoptosis

Routes of Administration

Goals & Uses

• Classical Hodgkin lymphoma (relapsed/refractory)OncologyHigh
• Primary cutaneous ALCL or CD30-expressing mycosis fungoidesOncologyHigh
• Systemic anaplastic large cell lymphoma (relapsed/refractory)OncologyHigh
• Previously untreated Stage III/IV cHL (with AVD)OncologyHigh
• Post-ASCT consolidation in cHL at high risk of relapseOncologyHigh
• Previously untreated CD30+ peripheral T-cell lymphomaOncologyHigh

Contraindications

• Known severe hypersensitivity to brentuximab vedotinHypersensitivityHigh
• Concurrent bleomycin useDrug CombinationHigh
• Progressive multifocal leukoencephalopathy (PML) riskNeurologicalHigh

Adverse Effects

• Progressive multifocal leukoencephalopathy (PML)NeurologicalRare
• Nausea and vomitingGastrointestinalCommon
• NeutropeniaHematologicCommonLow neutrophil count
• FatigueGeneralCommonLow energy or tiredness
• Peripheral sensory neuropathyNeurologicalCommon
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• BleomycinHigh
• Strong CYP3A4 inducers (e.g., rifampin)Moderate
• Strong CYP3A4 inhibitors (e.g., ketoconazole)Moderate
• P-glycoprotein inhibitorsModerate

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Hepatic impairment (moderate to severe)Organ ImpairmentRelative
• Pediatric patientsAgeRelative
• Severe renal impairment (CrCl <30 mL/min)Organ ImpairmentRelative
• BreastfeedingReproductiveAbsolute

Regulatory Status

• European UnionApprovedApproved: Relapsed/refractory CD30-positive Hodgkin lymphoma, Relapsed/refractory systemic ALCL, CD30-positive cutaneous T-cell lymphoma, Previously untreated CD30-positive HL in combination with AVDEMA approved October 2012 via conditional marketing authorization; subsequently converted to full approval for various indications
• United StatesApprovedApproved: Relapsed/refractory classical Hodgkin lymphoma, Relapsed/refractory systemic ALCL, Previously untreated Stage III/IV cHL in combination with chemotherapy, Post-ASCT consolidation in cHL at high risk of relapse or progression, Primary cutaneous ALCL or CD30-expressing mycosis fungoides, Previously untreated CD30-positive peripheral T-cell lymphomaFirst FDA approval August 2011 under accelerated approval; multiple supplemental approvals since. Boxed Warning for PML.
• United KingdomApprovedApproved: Relapsed/refractory classical Hodgkin lymphoma, Relapsed/refractory systemic ALCL, CD30-positive cutaneous T-cell lymphomaApproved by MHRA; NICE technology appraisals issued for specific indications with access restrictions in some settings

Approved by FDA in 2011 under accelerated approval; subsequent full approvals granted for multiple indications including first-line cHL with AVD, post-autologous stem cell transplant consolidation, pcALCL, and MF. EMA approved in 2012. Carries a Boxed Warning for progressive multifocal leukoencephalopathy (PML).

Evidence & Sources

No sources recorded yet.