A patient with relapsed Hodgkin lymphoma expresses CD30 strongly. He is started on brentuximab vedotin. Severe peripheral neuropathy developing during treatment results directly from:

• A Anti-CD30 antibody binding gangliosides on Schwann cells
• B Inhibition of microtubules by free antibody in dorsal root ganglia
• C Complement-mediated demyelination triggered by the antibody
• D Release of monomethyl auristatin E from the linker inside target cells and its diffusion into plasma ✓

Explanation

Brentuximab vedotin is an ADC linking anti-CD30 antibody via a cleavable valine-citrulline linker to MMAE, an anti-mitotic agent. After internalisation the linker is cleaved by lysosomal cathepsin, releasing MMAE, some of which escapes the target cell into circulation and enters tubulin-rich neurons, causing sensory neuropathy. The antibody itself does not bind nerve tissue; the payload's escape explains both neuropathy and neutropenia.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.