# POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma

Source: https://onco.cc/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/  
OnCo record `paper-polarix-polatuzumab-rchp-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Replacing one chemotherapy drug in R-CHOP with a CD79b antibody-drug conjugate modestly reduced progression (2-year PFS 76.7% versus 70.2%) without changing survival or side effects.

## Summary

POLARIX randomised 879 previously untreated patients with diffuse large B-cell lymphoma (IPI 2-5, age 18-80) to pola-R-CHP (polatuzumab vedotin replacing vincristine) or standard R-CHOP for six cycles plus two rituximab doses. The primary endpoint was investigator-assessed PFS. At two years PFS was 76.7% versus 70.2% (hazard ratio 0.73) while overall survival was identical (88.7% versus 88.6%) and the safety profiles were similar. Exploratory subgroups suggested most benefit in activated B-cell-like subtype, older patients and higher IPI, with little or no benefit in germinal-centre subtype. It was the first regimen to beat R-CHOP in two decades of trials.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2115304
- Authors: Tilly H, Morschhauser F, Sehn LH, et al.
- Findings: 879 untreated DLBCL patients, IPI 2-5; pola-R-CHP vs R-CHOP.; 2-year PFS 76.7% vs 70.2%; hazard ratio 0.73 (about 6.5 percentage points absolute).; 2-year overall survival 88.7% vs 88.6%; no difference.; Grade 3-4 adverse events 57.7% vs 57.5%; peripheral neuropathy rates similar.; Exploratory: benefit concentrated in ABC subtype, IPI 3-5 and age over 60; GCB subtype showed none.
- What it means: POLARIX gave the first new first-line standard for DLBCL since rituximab was added to CHOP, and pola-R-CHP is now approved and widely used, especially in higher-risk or ABC-type disease. The gain is modest and survival is unchanged, so many clinicians still use R-CHOP in lower-risk or GCB-type patients. Cost and subgroup uncertainty drive ongoing debate.
- Caveats: No overall survival benefit; the PFS gain is modest in absolute terms.; Subgroup effects are exploratory and hypothesis-generating, yet influence practice.; Excluded very low IPI (0-1) and age over 80.; High cost relative to a generic-based regimen.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2115304
- ClinicalTrials.gov NCT03274492: https://clinicaltrials.gov/study/NCT03274492

## Connected records

- 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/)
- key papers: [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/)
- trials: [POLAR BEAR](https://onco.cc/trials/polar-bear/), [POLARIX](https://onco.cc/trials/polarix/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [CD20](https://onco.cc/targets/cd20/), [CD79b](https://onco.cc/targets/cd79b/)
- drugs: [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Polatuzumab vedotin](https://onco.cc/drugs/polatuzumab-vedotin/), [Rituximab](https://onco.cc/drugs/rituximab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Gilles Salles](https://onco.cc/people/gilles-salles/), [Hervé Tilly](https://onco.cc/people/herve-tilly/)

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