SAN DIEGO — Patients with diffuse large B-cell lymphoma (DLBCL) continue to show superior progression-free survival at 5 years with first-line pola-R-CHP compared with the R-CHOP regimen, according to updated results of the phase 3 POLARIX study.
These findings “confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL,” said lead investigator Gilles Salles, MD, PhD, who presented the extended results at the American Society of Hematology (ASH) 2024 Annual Meeting.
Pola-R-CHP is a modified version of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in which vincristine is replaced with polatuzumab vedotin. The modified regimen was approved by the US Food and Drug Administration in April 2023 on the basis of 2-year results from the same study.
In POLARIX, researchers randomized 879 previously untreated adult patients with CD20-positive DLBCL (median age, 66 years) to six to eight 21-day cycles of treatment with either pola-R-CHP or R-CHOP. The primary endpoint was progression-free survival, and secondary endpoints included complete remission and overall survival.
The initial 2-year results — progression-free survival of 76.7% for pola-R-CHP vs 70.2% for R-CHOP — “were the first in 20 years” showing benefits for patients with DLBCL, said Salles, from Memorial Sloan Kettering Cancer Center, New York City.
In the current analysis, there were 879 patients in the global intention-to-treat population — 440 who received pola-R-CHP and 439 who received R-CHOP — and 873 in the safety analysis.
At the 5-year follow-up, Salles and colleagues observed a sustained and significant progression-free survival benefit in patients treated with pola-R-CHP compared with those who received R-CHOP (64.9% vs 59.1%; hazard ratio [HR], 0.77).
Patients receiving the modified regimen also demonstrated significantly higher rates of complete remission at 5 years (71.8% vs 66.5%; HR, 0.75). These data tell us that for patients who reach complete remission at the end of treatment, the vast majority are still in remission at 5 years, said Salles.
For patients who did progress, those treated with pola-R-CHP had fewer subsequent therapies than those treated with R-CHOP. This included radiotherapy (9.5% vs 14.1%), systemic therapy (20.0% vs 28.2%), platinum-based therapy (9.8% vs 15.5%), stem cell transplant (5.0% vs 8.4%), chimeric antigen receptor T-cell therapy (2.3% vs 4.1%), and bispecifics (1.4% vs 2.1%).
The 5-year overall survival, a secondary endpoint, was numerically better but not significantly so among patients treated with pola-R-CHP (82.3% vs 79.5%; HR, 0.85).
In a competing risk analysis, the cumulative incidence of lymphoma-related deaths at 5 years was 9.1% with pola-R-CHP vs 12.2% with R-CHOP. The probability of non-lymphoma–related deaths, including death due to study treatment, was similar between the two groups at 5 years — 8.56% with pola-R-CHP vs 8.93% with R-CHOP.
An exploratory analysis of progression-free survival and overall survival in subgroups of the patient population, including those with high-risk disease, showed a trend in favor of pola-R-CHP in almost all cases, but Salles warned that the analysis was underpowered.
“I think that interpreting this data to decide the care of the patient should be done very cautiously,” he said.
The researchers did not observe any new safety signals, with pola-R-CHP continuing to show a favorable benefit-risk profile. Looking at adverse events of all grades, Salles noted slightly less peripheral neuropathy with pola-R-CHP (50.3% vs 52.4%), slightly more infection (47.9% vs 44.0%), as well as a favorable trend for pola-R-CHP regarding cardiac arrhythmia (3.6% vs 5.2%) and carcinogenicity (1.0% vs 2.4%), and “very slight and tiny differences” in neutropenia (48.5% vs 45.8%), anemia (33.3% vs 30.1%), and thrombocytopenia (18.0% vs 17.3%).
While the researchers concluded that the study findings confirm pola-R-CHP as the standard of care for patients with previously untreated intermediate- or high-risk DLBCL, Ajay Major, MD, had some reservations.
The results confirm “a small but significant benefit” in progression-free survival and no significant difference in overall survival, but there is some question as to whether pola-R-CHP is appropriate for all-comers with intermediate- or high-risk DLBCL, noted Major, a lymphoma specialist and assistant professor of medicine at the University of Colorado School of Medicine, Aurora, Colorado, who was not involved in this analysis.
“The subgroup analysis in POLARIX for efficacy of pola-R-CHP based on cell of origin is not adequately powered, and further dedicated on this question studies are needed,” Major told Medscape Medical News.
One study presented at the meeting by Major’s group concluded that cell of origin is a strong predictor of the activity of pola-containing therapy in patients with relapsed/refractory large B-cell lymphoma, while another analysis of POLARIX showed progression-free survival and overall survival benefits of pola-R-CHP over R-CHOP in patients with the activated B-cell subtype of DLBCL but not those with the germinal center B-cell subtype, Major noted.
“I think many oncologists will extrapolate from these other data sources and preferentially use pola-R-CHP in patients with activated B-cell or non-germinal center DLBCL,” he predicted.
The study was funded by F. Hoffmann-La Roche/Genentech.
Salles reported disclosures with the following companies: BeiGene (consultancy), AbbVie (consultancy, research funding), Genentech/Roche (consultancy, research funding), Incyte (consultancy), BMS/Celgene (consultancy), among others. Major reported the following disclosures with Roche/Genentech (consultancy), GSK (research funding), and Incyte (research funding).
Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.
