# Polatuzumab vedotin

Source: https://onco.cc/drugs/polatuzumab-vedotin/  
OnCo record `polatuzumab-vedotin` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Polatuzumab vedotin is an ADC against CD79b that, swapped into the classic R-CHOP regimen, became the first improvement on frontline lymphoma therapy in twenty years.

## Summary

POLARIX (2022): Pola-R-CHP versus R-CHOP in untreated DLBCL, IPI 2-5. Two-year PFS 76.7% vs 70.2% (HR 0.73); five-year PFS 64.9% vs 59.1% (HR 0.77) with OS HR 0.85, not significant. Approved US April 2023 for frontline DLBCL (IPI ≥2) and since 2019 with bendamustine-rituximab for relapsed disease. Peripheral neuropathy is the class toxicity.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Polivy
- Modality: ADC
- Mechanism: Humanised anti-CD79b IgG1 internalised via the B-cell receptor complex; MMAE released by cathepsin B; bystander killing.
- Payload: MMAE (tubulin inhibitor), DAR ~3.5
- Linker: mc-vc-PABC, protease-cleavable
- Approvals: US 2019: Relapsed/refractory DLBCL with bendamustine-rituximab after ≥2 lines (accelerated); US 2023: Untreated DLBCL, IPI ≥2, with R-CHP (Pola-R-CHP)
- Dosing: IV; 1.8 mg/kg every 21 days for 6 cycles with R-CHP (frontline) or with BR (relapsed)
- Toxicity (grade 3+): Peripheral neuropathy 1.6%; Neutropenia 28.3%; Febrile neutropenia 13.8%

## Notes

- Lymphoma biology: CD79b is chosen not because it is more specific than CD20 but because it internalises. It is part of the B-cell receptor complex, which is continuously taken into the cell, so it can carry monomethyl auristatin E inside; CD20 cannot. Expression is above 95% in diffuse large B-cell lymphoma, so nothing is tested before the first dose, and the dose-limiting toxicity is the payload, as cumulative peripheral neuropathy, rather than the antigen (Davis 2010).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Polatuzumab_vedotin
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Polatuzumab%20vedotin
- Davis et al., Nature 2010: chronic active B-cell receptor signalling in diffuse large B-cell lymphoma: https://doi.org/10.1038/nature08638

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [CD79b](https://onco.cc/targets/cd79b/)
- companies: [Chugai Pharmaceutical](https://onco.cc/companies/chugai/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [British and American lymphoma practice: where they differ, and why](https://onco.cc/terms/lymphoma-tx-uk-versus-us/), [Bystander effect (ADC)](https://onco.cc/terms/bystander-effect/), [Payload (ADC)](https://onco.cc/terms/payload/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/), [What the NHS in England funds for lymphoma, appraisal by appraisal](https://onco.cc/terms/lymphoma-tx-uk-access/)
- trials: [A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)](https://onco.cc/trials/nct06890884/), [A Study to Evaluate the Safety and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With Polatuzumab Vedotin in B-Cell Non-Hodgkin Lymphoma](https://onco.cc/trials/nct03671018/), [An Open-Label Phase lB/II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma](https://onco.cc/trials/nct03533283/), [Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients](https://onco.cc/trials/nct04844866/), [POLAR BEAR](https://onco.cc/trials/polar-bear/), [POLARGO](https://onco.cc/trials/polargo/), [POLARIX](https://onco.cc/trials/polarix/), [SUNMO](https://onco.cc/trials/sunmo/)
- drugs: [Mosunetuzumab](https://onco.cc/drugs/mosunetuzumab/)
- pairings: [CD20 bispecific + CD79b ADC (mosunetuzumab + polatuzumab)](https://onco.cc/pairings/bispecific-plus-adc-lymphoma/)
- ideas: [ctDNA-guided escalation and de-escalation in frontline DLBCL](https://onco.cc/ideas/idea-ctdna-guided-dlbcl-frontline/)
- biomarkers: [CD79B ITAM mutation](https://onco.cc/biomarkers/cd79b-itam-mutation/)
- key papers: [POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/), [Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial](https://onco.cc/key-papers/paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)

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