Pola-R-CHP Is Associated With Improved 2-Year PFS Rates in Older Untreated DLBCL Population

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The benefit:risk was favored with polatuzumab vedotin-piiq (Polivy) plus rituximab (Rituxan), cyclophosphamide, doxorubicin (Adriamycin), and prednisone (Pola-R-CHP) compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in older patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to data from a post hoc subgroup analysis from the phase 3 POLARIX trial (NCT03274492).1

Data from the analysis, published in Blood Advances, demonstrated that older patients with previously untreated DLBCL had clinically improved 2-year progression-free survival (PFS) rates when treated with Pola-R-CHP vs R-CHOP. Specifically, patients aged 60 years or older in the Pola-R-CHP arm (n = 311) showed 2-year PFS rates at 77.9% (95% CI, 73.3%-82.6%) vs 70.3% (95% CI, 65.1%-75.4%) in those from the R-CHOP arm (n = 318). Additionally, the 2-year PFS rates for patients in the Pola-R-CHP and R-CHOP arms, respectively, who are 65 years of age and older, 70 years of age and older, and 75 years of age and older were 76.5% (n = 231; 95% CI, 71.0%-82.0%) vs 68.4% (n = 236; 95% CI, 62.4%-74.5%), 77.3% (n = 141; 95% CI, 70.3%-84.3%) vs 67.0% (n = 143; 95% CI, 59.2%-74.8%), and 78.9% (n = 60; 95% CI, 68.3%-89.5%) vs 68.9% (n = 60; 95% CI, 57.0%-80.8%).

At a data cutoff of June 15, 2022, and a median survival follow-up of 40 months, treatment of Pola-R-CHP demonstrated clinically meaningful PFS improvements across the 4 patient age groups from the post hoc subgroup analysis. Notably, patients in the 70 years of age and older group showed significant PFS improvement, in which Pola-R-CHP reduced the risk of disease progression, relapse, or death by 37% vs R-CHOP (unstratified HR, 0.63; 95% CI, 0.41-0.96). Patients from the 75 years of age and older group also demonstrated clinically meaningful PFS improvement (unstratified HR, 0.50; 95% CI, 0.25-1.02).

“In this analysis of older patients (aged ≥60 years) with previously untreated DLBCL in the phase 3 POLARIX study, the benefit-risk profile favored Pola-R-CHP over R-CHOP,” the study authors wrote in the publication. “Efficacy end points favored Pola-R-CHP vs R-CHOP across all age groups studied, including superior PFS in the older age groups (≥70 and ≥75 years).”

Background and POLARIX Study Design

At the 2024 ASH Annual Meeting, findings from the 5-year extended follow-up of the phase 3 trial were presented, which confirmed the results from the primary analysis of PFS at 2 years.2 Notably, at a median follow-up of 54.9 months with a data cutoff of July 5, 2024, the 5-year PFS rates were 64.9% (95% CI, 59.8%-70.0%) in the Pola-R-CHP (n = 440) arm, and 59.1% (95% CI, 54.0%-64.3) and placebo/R-CHOP arm (n = 439; HR, 0.77; 95% CI, 0.62-0.97).

Of note, in June 2019, the FDA granted accelerated approval to polatuzumab vedotin, an antibody-drug conjugate (ADC), combined with bendamustine/rituximab (Rituxan)for the treatment of patients with relapsed/refractory DLBCL who were previously treated with at least 2 therapies.3 Furthermore, the FDA approved polatuzumab vedotin plus R-CHP in April 2023 for the treatment of patients with previously untreated DLBCL not otherwise specified or those with high-grade B-cell lymphoma with an International Prognostic Index (IPI) score of 2 or greater.4

The randomized, double-blind study evaluated Pola-R-CHP compared with R-CHOP for the treatment of patients with previously untreated, CD20-positive DLBCL with an ECOG performance status of 0 to 2, and an IPI score of 2 to 5.1 Specifically, the post hoc subgroup analysis evaluated the efficacy and safety of the regimens based on age, with a subgroup of older patients 60 to 80 years of age at enrollment. The ages included those 60 years of age and older, 65 years of age and older, 70 years of age and older, and 75 years of age and older.

Patients were randomly assigned 1:1 to be treated with 6 21-day cycles of treatment. These included intravenous (IV) rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2, and doxorubicin at 50 mg/m2 on day 1 plus oral prednisone at 100 mg once daily on days 1 through 5. Those in the Pola-R-CHP arm then received polatuzumab vedotin at 1.8 mg/kg on day 1; those treated in the R-CHOP arm also received a placebo plus vincristine at 1.4 mg/m2 with a maximum of 2 mg on day 1. Moreover, rituximab monotherapy at 375 mg/m2 was given for an additional 2 cycles.

The primary end point was PFS as assessed by the investigator. Secondary end points included event-free survival (EFS), complete response (CR) rate by blinded independent central review (BICR), overall survival (OS), and disease-free survival (DFS).

Baseline Patient Characteristics

In the subgroup of older patients from the Pola-R-CHP and R-CHOP arms, respectively, patients identifying as male comprised 51.8% vs 52.8% (≥60 years of age group), 49.8% vs 52.1% (≥65 years of age group), 46.1% vs 49.0% (≥ 70 years of age group), and 48.3% vs 50.0% (≥75 years of age group) of the population. Of note, most patients from all age groups had stage III to IV disease (≥60 years, 86.5% vs 85.2%; ≥65 years, 88.33% vs 85.6%; ≥70 years, 87.9% vs 84.6%; ≥75 years, 83.3% vs 80.0%). The most common extranodal sites included 0 or 1 (57.9% vs 56.0%; 54.1% vs 56.4%; 54.6% vs 53.8%; 58.3% vs 51.7%). Most patients had an ECOG performance status of 0 or 1 (85.5% vs 84.9%; 84.0% vs 84.7%; 84.4% vs 86.0%; 83.3% vs 81.7%) and an IPI score of 3 to 5 (67.8% vs 69.1%; 71.4% vs 69.5%; 70.2% vs 69.2%; 71.7% vs 66.7%). The cell of origin was mostly derived from the germinal center B cell (55.3% vs 45.2%; 56.6% vs 45.5%; 60.2% vs 44.7%; 57.1% vs 51.1%).

Additional Efficacy and Safety Data

The objective response rate (ORR) in the Pola-R-CHP and R-CHOP arms based on the 60 years of age or older group, 65 years of age or older group, 70 years of age or older group, and the 75 years of age or older group. Specifically, the respective ORRs were 86.2% vs 84.9%, 84.0% vs 84.8%, 86.5% vs 83.9%, and 85.0% vs 81.7%. Across all age groups, the majority of patients achieved complete responses (80.7% vs 76.1%; 78.4% vs 75.9%; 81.6% vs 77.6%; 78.3% vs 76.7%).

In the Pola-R-CHP and R-CHOP arms, the 2-year OS rates were not significantly different, particularly in the 60 years of age and older and 65 years of age and older groups, respectively (88.6% [95% CI, 85.0-92.1%] vs 87.4% [95% CI, 83.7%-91.1%]; 85.9% [95% CI, 81.4%-90.4%] vs 86.5% [95% CI, 82.0%-90.9%]). At the data cutoff, 2-year EFS and DFS rates showed improvements with Pola-R-CHP compared with R-CHOP in all 4 age groups. However, those in the 70 years of age and older and 75 years of age and older groups demonstrated the greatest improvement with Pola-R-CHP vs R-CHOP. Of note, the 2-year EFS rates with Pola-R-CHP vs R-CHOP in these 2 respective age groups were 77.3% (95% CI, 70.3%-84.3%) vs 66.3% (95% CI, 58.4%-74.2%) and 78.9% (95% CI, 68.3%-89.5%) vs 67.2% (95% CI, 55.1%-79.3%). Additionally, the respective 2-year DFS rates were 81.3% (95% CI, 74.4%-88.2%) vs 73.0% (95% CI, 65.1%-80.9%) and 82.7% (95% CI, 72.4%-93.0%) vs 72.8% (95% CI, 60.6%-85.0%).

Regarding safety, treatment exposure was high in both treatment arms, with most patients receiving all 6 doses of polatuzumab in the Pola-R-CHP arm (90.2%) or vincristine in the R-CHOP arm (88.3%). Notably, the safety profiles were comparable for Pola-R-CHP vs R-CHOP in patients 60 years of age and older and 65 years of age and older; increased incidence of toxicities was observed in the 70 years of age and older and 75 years of age and older groups. The most common grade 3 or 4 treatment-emergent adverse effects (TEAEs) across the 4 age groups were neutropenia, febrile neutropenia, and anemia. Those in the 70 years of age and older and 75 years of age and older groups showed higher rates of serious AEs, with grade 3 or 4 febrile neutropenia, diarrhea, and infection occurring in the Pola-R-CHP arm compared with the R-CHOP arm.

“In the overall POLARIX population, the safety profile was generally similar between treatment arms, and the most common grade 3/4 AE was neutropenia,” the study authors concluded. “Although there was a higher rate of grade 3/4 AEs observed in this analysis with Pola-R-CHP than with R-CHOP, the safety profile in older patients was similar across all age groups and generally consistent with that reported in the overall population of POLARIX (aged 18-80 years).”

References

1. Hu B, Reagan PM, Sehn LH, et al. Subgroup analysis of older patients ≥60 years with diffuse large B-cell lymphoma in the phase 3 POLARIX study. Blood Adv. 2025;9(10):2489-2499. doi:10.1182/bloodadvances.2024014707
2. Five-year analysis of the POLARIX study: Prolonged follow-up confirms positive impact of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) on outcomes. Salles G, Morschhauser F, Sehn LH, et al. Blood. 2024;144(suppl 1):469. doi:10.1182/blood-2024-197938
3. FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. FDA. June 10, 2019. Accessed May 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-diffuse-large-b-cell-lymphoma
4. FDA approves polatuzumab vedotin-piiq for previously untreated diffuse large B-cell lymphoma, not otherwise specified, and high-grade B-cell lymphoma. FDA. Updated April 20, 2023. Accessed May 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-previously-untreated-diffuse-large-b-cell-lymphoma-not