Polatuzumab Vedotin
Anti-CD79b antibody-drug conjugate with MMAE payload for relapsed or refractory diffuse large B-cell lymphoma.
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~150 kDa (ADC) |
| Peptide Payload | Monomethyl auristatin E (MMAE) |
| Linker | Valine-citrulline (protease-cleavable) |
| DAR | ~3.5 |
| Target | CD79b |
Structure
Polatuzumab vedotin (Polivy) is a humanized anti-CD79b IgG1 monoclonal antibody conjugated to MMAE via a valine-citrulline cleavable linker. CD79b is a component of the B-cell receptor complex expressed on most B-cell malignancies.
Mechanism of Action
The antibody binds CD79b on B-cell lymphoma cells, inducing receptor-mediated endocytosis. Lysosomal cleavage releases MMAE, which binds tubulin and inhibits microtubule assembly, causing G2/M arrest and apoptosis. The conjugate is combined with bendamustine and rituximab for enhanced efficacy.
Clinical Applications
- Diffuse large B-cell lymphoma: Relapsed/refractory with bendamustine-rituximab (Polivy)
- First-line DLBCL: With R-CHP (POLARIX trial)
- Follicular lymphoma: Under investigation
- Mantle cell lymphoma: Early clinical data
Pharmacokinetics
- Half-life: ~12 days
- Steady state: ~42 days
- Cmax (MMAE): ~3.5 ng/mL
- Metabolism: MMAE by CYP3A4
- Route: IV infusion every 3 weeks (1.8 mg/kg)
Safety and Side Effects
Neutropenia (46%), peripheral neuropathy (40%), fatigue, diarrhea, nausea, thrombocytopenia, anemia, and infections. Tumor lysis syndrome risk with high tumor burden. Requires G-CSF support in most patients.
References
- Sehn, L.H., et al. (2019). Polatuzumab vedotin with BR for DLBCL. New England Journal of Medicine, 382, 2209-2219.
- Tilly, H., et al. (2022). POLARIX: polatuzumab vedotin with R-CHP. New England Journal of Medicine, 386, 351-363.
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