Clinical trialPhase 3Lymphoma

Five-Year Outcomes of the POLARIX Study Comparing Pola-R-CHP and R-CHOP in Patients With Diffuse Large B-Cell Lymphoma

J Clin Oncol · 2025879 patients (global intention-to-treat population)

Morschhauser F, Salles G, Sehn LH, et al. J Clin Oncol. 2025. 43:3698-3705

Study type: Clinical trial
Study name: POLARIX
Phase: Phase 3
Design: Randomised trial; updated 5-year follow-up report (median follow-up 64.1 months)
Sample size: 879 patients (global intention-to-treat population)
Source: J Clin Oncol · 2025
Trial registration: NCT03274492

In plain words

Diffuse large B-cell lymphoma is the most common type of aggressive lymphoma, and for years its first treatment has been the R-CHOP regimen. In the POLARIX study, the new regimen replaced the drug vincristine with the targeted drug polatuzumab vedotin. After about five years of follow-up, patients who had the new regimen more often stayed free of the disease coming back or getting worse (about 65% vs 59%). The difference in overall survival is not yet statistically certain, but deaths from lymphoma were fewer in the new-regimen group, and the long-term side effects of the two regimens were similar.

Key results

64.9% vs 59.1%

Five-year PFS

HR 0.77 (95% CI: 0.62 to 0.97); median follow-up 64.1 months

HR 0.85

Overall survival (5-year data cut)

95% CI: 0.63 to 1.15; not statistically significant (HR 0.94 at the 2-year cut)

46 vs 62 patients

Lymphoma-related deaths (expanded population)

Pola-R-CHP vs R-CHOP

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), 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. Prophylactic G-CSF was mandatory in the first 6 cycles.

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 original POLARIX report 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 with untreated intermediate-‎ or high-risk diffuse large B-cell lymphoma (DLBCL).

Endpoints

Primary endpoint: progression-free survival (PFS).

Other endpoints: overall survival (OS), lymphoma-related death, exploratory subgroup analyses and long-term tolerability.

Safety and side effects

Long-term tolerability was similar in the two treatment groups. The abstract does not report detailed adverse event figures.

Clinical significance and place in guidelines

This five-year follow-up confirms the durable progression-free survival benefit of Pola-R-CHP, and the authors consider it a standard first-line treatment for DLBCL. The overall survival benefit has not reached statistical significance, so the choice between Pola-R-CHP and R-CHOP should still be based on patient characteristics and disease risk.

Limitations

The overall survival difference was not statistically significant. Findings in high-risk subgroups (activated B-cell type, IPI 3 to 5) are exploratory. The abstract does not report detailed adverse event figures.

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.