Polatuzumab vedotin-piiq (Polivy) plus R-CHP (rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone; pola-R-CHP) has sustained its role in the first-line diffuse large B-cell lymphoma (DLBCL) treatment paradigm based on long-term progression-free survival (PFS) data and findings from subgroup analyses, according to Samina Hirani, MD.
In December 2023, the FDA approved pola-R-CHP for the treatment of adult patients with previously untreated DLBCL not otherwise specified or high-grade B-cell lymphoma with an IPI score of 2 or greater.1 This regulatory decision was supported by findings from the phase 3 POLARIX trial (NCT03274492), which evaluated pola-R-CHP vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in this population. Patients who received pola-R-CHP (n = 440) achieved a statistically significant PFS benefit vs those who received R-CHOP (n = 439; HR, 0.73; 95% CI, 0.57-0.95; P = .0177). The 2-year PFS rates were 76.7% (95% CI, 72.7%-80.8%) and 70.2% (95% CI, 65.8%-74.6%), respectively.2
Long-term follow-up data from POLARIX showed that at a median follow-up of 54.9 months, the 5-year PFS rate was 64.9% (95% CI, 59.8%-70.0%) with pola-R-CHP vs 59.1% (95% CI, 54.0%-64.3%) with R-CHOP (HR, 0.77; 95% CI, 0.62-0.97).3
“R-CHOP remains an efficacious backbone therapy,” Hirani said in an interview with OncLive. “However, pola-R-CHP provides a good alternative for the high-risk population, especially patients with high International Prognostic Index [IPI] scores and ABC subtype.”
In the interview, Hirani discussed the evolving first-line treatment paradigm for patients with DLBCL, the historically unprecedented findings from POLARIX, subgroup analyses from the trial that may further refine patient care, and the clinical relevance of pola-R-CHP as an alternative to R-CHOP in select patients.
Hirani is a hematologist/oncologist in the Mayo Clinic Health System in Eau Claire, Wisconsin.
OncLive: What were some of the key efficacy findings from the POLARIX trial?
Hirani: The POLARIX 2-year analysis met its primary end point of PFS [favoring pola-R-CHP] with a hazard ratio of 0.73. This is the first [DLBCL] trial in approximately 20 years to show a PFS benefit [with an investigational therapy]. The [most recent positive] trial prior to this was the R-CHOP trial led by Bertrand Coiffier, MD, PhD, et al [in patients with DLBCL]. Interesting subgroup analyses were done out of POLARIX that showed similar efficacy in an older population. Another subgroup analysis done on the cell of origin—GCB vs ABC—and a profound benefit [was observed with] the polatuzumab-based regimen in patients with the ABC subtype, as well as in those with higher IPI scores.
At the 2024 ASH Annual Meeting, data from the 5-year analysis for POLARIX [were presented]. That showed a consistent PFS benefit [with pola-R-CHP] that remained statistically significant. At the 5-year point, the median overall survival was numerically higher [with pola-R-CHP, but this difference] remained statistically nonsignificant.
What are some potential implications of the long-term efficacy data with pola-R-CHP in DLBCL?
[Pola-R-CHP] is a good alternative option to R-CHOP. [We should consider] this regimen in patients with higher IPI scores who historically tend to have high-risk disease and poor prognosis compared with the lower-risk population. They tend to have poor survival in comparison. Pola-R-CHP provides a good alternative and a clinically meaningful PFS benefit for patients and leads to a reduction in the need for subsequent therapies. That is clinically meaningful for patients because we know subsequent [treatments pose] a lot of burden regarding their finances, mental health, and physical health.
How do data with R-CHOP and pola-R-CHP inform treatment decision-making?
As the FDA approval [for pola-R-CHP in DLBCL] stands, it should be considered in all patients with IPI scores of 2 to 5. Although the subgroup analysis showed the most benefit in the ABC subtype, clinically, it’s hard to implement that subgroup analysis because those trials were conducted using gene expression profiling. In clinical practice, we use immunohistochemistry algorithms to determine cell of origin, so we have a chance to miss approximately 20% of patients [with the ABC subtype]. Currently, selecting [patients for pola-R-CHP] based on cell of origin seems a little premature unless we are doing gene expression profiling.
What questions still need to be addressed regarding the use of pola-R-CHP in clinical practice?
One finding we all would like to explore further is the differential benefit of polatuzumab based on the cell of origin. A lot of relapsed/refractory trials using polatuzumab have previously shown this differential benefit in the ABC subtype. [We need] more exploration into how we can incorporate cell of origin to provide more individualized care for patients.
What treatment developments are on the horizon in LBCL?
A lot of new frontline approaches are coming up [in the near future]. [Strategies] moving beyond R-CHOP and investigating more novel therapies, such as CAR T-cell therapy, are ongoing in the frontline setting for untreated LBCL. Those hold a lot of promise based on the earlier data that have been presented.
[We may also see] bispecific antibodies moving into the frontline setting. [The field is] moving beyond chemotherapy-based approaches. We look forward to these ongoing clinical trials that are actively recruiting, and we await the results to see how they pan out for patients.
References
[Ad hoc announcement pursuant to Art. 53 LR] FDA approves Roche’s Polivy in combination with R-CHP for people with certain types of previously untreated diffuse large B-cell lymphoma. News release. Roche. April 19, 2023. Accessed August 28, 2025. https://www.roche.com/media/releases/med-cor-2023-04-19
Mehta-Shah N, Tilly H, Morschhauser F, et al. Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): results from the phase III POLARIX study. Presented at: 2022 Pan Pacific Lymphoma Conference; July 18-22, 2022; Koloa, HI.
Salles G, Morschhauser F, Sehn LH, et al. 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. Blood. 2024;144(suppl 1):469. doi:10.1182/blood-2024-197938