Clinical trialPhase 3Blood cancers (leukaemia, lymphoma and myeloma)Lymphoma

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

N Engl J Med · 2022879 patients (440 pola-R-CHP, 439 R-CHOP)

Tilly H, Morschhauser F, Sehn LH, et al. N Engl J Med. 2022. 386:351-363

A newer report of this study has been published: Five-Year Outcomes of the POLARIX Study Comparing Pola-R-CHP and R-CHOP in Patients With Diffuse Large B-Cell Lymphoma (2025)

Study type: Clinical trial
Study name: POLARIX
Phase: Phase 3
Design: Randomised (1:1), double-blind, placebo-controlled, international trial
Sample size: 879 patients (440 pola-R-CHP, 439 R-CHOP)
Source: N Engl J Med · 2022
Trial registration: NCT03274492

In plain words

For about 20 years, the standard treatment for diffuse large B-cell lymphoma was the R-CHOP regimen. In this study, replacing one of the drugs in this regimen (vincristine) with the targeted drug polatuzumab vedotin — which, like a "guided missile", delivers a toxin straight to the lymphoma cell — lowered the chance of the disease coming back, without more side effects overall. In this report, survival did not differ between the two groups.

Key results

76.7% vs 70.2%

2-year progression-free survival

HR 0.73 (95% CI: 0.57 to 0.95); P = 0.02; median follow-up 28.2 months

88.7% vs 88.6%

2-year overall survival

HR 0.94 (95% CI: 0.65 to 1.37); P = 0.75 (no difference)

Drugs in this study:Cyclophosphamide (Endoxan)Doxorubicin (Adriamycin)Rituximab (Rituxan/MabThera)

Dose and schedule cards

Pola-R-CHP (POLARIX trial)

First-line DLBCL with IPI 2 to 5, age 18 to 80 years, ECOG 0–2 (the EHA guideline’s preferred regimen for IPI 2 to 5)Cycle length: Every 21 daysOn the page “Lymphoma” · Treatment regimens and dosing: first-line DLBCL

First-line DLBCL with IPI 2 to 5, age 18 to 80 years, ECOG 0–2 (the EHA guideline’s preferred regimen for IPI 2 to 5)

Drug	Dose	Route	Schedule
Polatuzumab vedotin	1.8 mg/kg	IV	Day 1
Rituximab	375 mg/m²	IV	Day 1
Cyclophosphamide	750 mg/m²	IV	Day 1
Doxorubicin	50 mg/m²	IV	Day 1
Prednisone	100 mg daily	Oral	Days 1–5

Cycle length: Every 21 days
Duration: 6 cycles of Pola-R-CHP followed by 2 doses of single-agent rituximab (cycles 7 and 8)

Doses and eligibility criteria from the full text of POLARIX; EHA preference. Per the label: prophylactic G-CSF is mandatory; Pneumocystis and herpes prophylaxis throughout treatment; premedication with an antihistamine and an antipyretic; tumour lysis syndrome prophylaxis in high-risk patients. For neuropathy, the polatuzumab dose is reduced to 1.4 and then 1 mg/kg, and if it is discontinued, R-CHP is continued. No clear benefit was seen in the subgroups aged under 60 years, with GCB type, with bulky disease or with lower IPI.

On the page “Lymphoma” · Treatment regimens and dosing: first-line DLBCL

R-CHOP-21

First-line DLBCL (standard treatment; for IPI 2 to 5, an acceptable alternative to Pola-R-CHP)Cycle length: Every 21 daysOn the page “Lymphoma” · Treatment regimens and dosing: first-line DLBCL

First-line DLBCL (standard treatment; for IPI 2 to 5, an acceptable alternative to Pola-R-CHP)

Drug	Dose	Route	Schedule
Rituximab	375 mg/m²	IV	Day 1
Cyclophosphamide	750 mg/m²	IV	Day 1
Doxorubicin	50 mg/m²	IV	Day 1
Vincristine	1.4 mg/m² (maximum 2 mg)	IV	Day 1
Prednisone	100 mg daily	Oral	Days 1–5

Cycle length: Every 21 days
Duration: 6 cycles of R-CHOP followed by 2 doses of single-agent rituximab (cycles 7 and 8), as in POLARIX

Doses from the full text of POLARIX (R-CHOP arm); the rituximab label for DLBCL specifies up to 8 infusions, on Day 1 of each cycle. In POLARIX, primary prophylactic G-CSF was mandatory during the first 6 cycles, and central nervous system prophylaxis was permitted according to institutional practice.

On the page “Lymphoma” · Treatment regimens and dosing: first-line DLBCL

Pola-R-CHP

Diffuse large B-cell lymphoma, first line, IPI 2 to 5Cycle length: Every 21 daysOn the page “Pola-R-CHP in DLBCL”

Diffuse large B-cell lymphoma, first line, IPI 2 to 5

Drug	Dose	Route	Schedule
Cycles 1 to 6
Polatuzumab vedotin	1.8 mg/kg	IV	Day 1
Rituximab	375 mg/m²	IV	Day 1
Cyclophosphamide	750 mg/m²	IV	Day 1
Doxorubicin	50 mg/m²	IV	Day 1
Prednisone	100 mg	Oral	Days 1 to 5
Cycles 7 and 8
Rituximab	375 mg/m²	IV	Day 1

Cycle length: Every 21 days
Duration: 6 cycles, then 2 cycles of rituximab alone

As in POLARIX.

Dose source:.

On the page “Pola-R-CHP in DLBCL”

R-CHOP (cyclophosphamide component)

Diffuse large B-cell lymphomaCycle length: Every 21 daysOn the page “Cyclophosphamide (Endoxan)” · Regimens and dosing

Diffuse large B-cell lymphoma

Drug	Dose	Route	Schedule
Cyclophosphamide	750 mg/m²	IV	Day 1

Cycle length: Every 21 days
Duration: Six cycles in POLARIX (plus 2 cycles of rituximab alone)

The same cyclophosphamide dose in Pola-R-CHP.

On the page “Cyclophosphamide (Endoxan)” · Regimens and dosing

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1pola-R-CHP

Six 21-day cycles: polatuzumab vedotin 1.8 mg/kg IV on day 1 (with vincristine placebo), plus rituximab 375 mg/m², cyclophosphamide 750 mg/m² and doxorubicin 50 mg/m² IV on day 1 and prednisone 100 mg orally on days 1 to 5; then cycles 7 and 8 of rituximab 375 mg/m² alone.

2R-CHOP

Six 21-day cycles of R-CHOP with vincristine 1.4 mg/m² (maximum 2 mg) on day 1 (with polatuzumab placebo) and the same doses of rituximab, cyclophosphamide, doxorubicin and prednisone; then two cycles of rituximab alone.

Source of the regimen details: Full text of the paper in PMC (PMC11702892), Methods section

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 to 80 with untreated intermediate-‎ or high-risk diffuse large B-cell lymphoma (DLBCL) (International Prognostic Index, IPI 2 to 5).

Endpoints

Primary endpoint: investigator-assessed progression-free survival.

Secondary endpoints: overall survival, event-free survival, complete response at end of treatment and safety.

Safety and side effects

The safety profile was similar in the two groups. The most common grade 3 or higher adverse events with pola-R-CHP versus R-CHOP: neutropenia 28.3% vs 30.8%, febrile neutropenia 13.8% vs 8.0% and anaemia 12.0% vs 8.4%. Peripheral neuropathy of any grade 52.9% vs 53.9% (full text of the paper).

Clinical significance and place in guidelines

The first regimen in two decades to outperform R-CHOP in a phase 3 trial. Pola-R-CHP was approved for untreated DLBCL by the EMA in 2022 and by the FDA in April 2023, and is now a first-line option in guidelines for patients with IPI 2 or higher. The lack of an overall survival benefit and differences in effect between subgroups (greater in the ABC type) mean that the choice between pola-R-CHP and R-CHOP is individualised.

Limitations

The absolute progression-free survival benefit was modest (about 6.5 percentage points at 2 years) and no difference in overall survival was seen. Patients with IPI zero and one were not enrolled. Subgroup analyses (such as greater benefit in the activated B-cell type and less in the germinal centre type) are exploratory.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.