Polatuzumab Vedotin Combo Improves OS Vs Rituximab/Chemo in R/R DLBCL

Patients with R/R DLBCL given polatuzumab vedotin, rituximab, gemcitabine, and oxaliplatin had an OS of 19.5 months.

Outcomes were improved when polatuzumab vedotin (Polivy) plus rituximab (Rituxan), gemcitabine, and oxaliplatin (Pola-R-GemOx) was used to treat patients who were transplant-ineligible with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) vs R-GemOx alone, according to results from the phase 3 POLARGO trial (NCT04182204) presented at the 2025 European Hematology Association Congress.

The median overall survival (OS) was 19.5 months in the Pola-R-GemOx arm vs 12.5 months in the R-GemOx arm (stratified HR, 0.60; 95% CI, 0.43-0.83; P = .0017). A reduction in the relative risk of death by 40% was observed in the Pola-R-GemOx arm compared with R-GemOx alone. The event-free rate at 24 months was 44.0% vs 33.2% between the 2 arms, respectively.

The median progression-free survival (PFS) was 7.4 months (95% CI, 6.2-11.7) in the Pola-R-GemOx arm and 2.7 months (95% CI, 2.4-3.3) in the R-GemOx arm (stratified HR, 0.37; 95% CI, 0.27-0.51; P <.0001).

The overall response rate (ORR) in the Pola-R-GemOx arm was 52.7%, with 12.4% of patients having a partial response (PR) and 40.3% having a complete response (CR). In the R-GemOx arm, the ORR was 24.6%, 5.6% had a PR, and 19.0% had a CR. The difference in CR was 21.3% (95% CI, 9.6%-32.9%; P = .0001).

“The POLARGO data reinforce the benefit of combining polatuzumab vedotin with chemotherapy in the treatment of DLBCL,” Matthew Matasar, MD, chief in the Division of Blood Disorders at the Rutgers Cancer Institute, professor of medicine at the Rutgers Robert Wood Johnson Medical School, and editorial advisory board member of the journal ONCOLOGY, said during the press briefing.

The trial enrolled 270 patients with relapsed/refractory DLBCL, not otherwise specified, or history of transformation of indolent disease to DLBCL; relapsed/refractory disease after 1 or more prior lines of therapy; or if they were treatment ineligible.

A total of 255 patients were randomly assigned 1:1 and were given either 1.8 mg/kg of polatuzumab vedotin plus 375 mg/m2 of rituximab, 1000 mg/m2 of gemcitabine, and 100 mg/m2 of oxaliplatin every 3 weeks for up to 8 cycles (n = 129); or matched R-GemOx every 3 weeks for up to 8 cycles (n = 126).

The primary end point was OS and key secondary end points were PFS by investigator, CR by independent review committee (IRC), and ORR by IRC.

The safety run-in enrolled 15 patients who were given Pola-R-GemOx every 3 weeks for up to 8 cycles. The primary end point was safety and tolerability.

Between the Pola-R-GemOx arm and the R-GemOx arm, the median number of cycles was 7.5 vs 4.0, and the median treatment duration was 4.8 months vs 2.1 months. Treatment-related adverse effects (AEs) occurred in 92.2% vs 82.4%, grade 3/4 AEs in 57.0% vs 58.4%, and treatment-related serious AEs in 28.1% vs 22.4%. Treatment-related grade 5 AEs occurred in 3.1% vs 2.4%. Patients discontinued the study drug because of AEs in 23.4% vs 8.0%, and experienced dose reduction because of AEs in 24.2% vs 11.2%.

Peripheral neuropathy occurred in 57.0% of patients in the Pola-R-GemOx arm and 28.8% in the R-GemOx arm, with grade 1 occurring in 37.5% vs 23.2%, grade 2 in 15.6% vs 5.6%, and grade 3 in 3.9% vs 0.0%. Thrombocytopenia was noted in 53.1% vs 40.8%, and grade 3 or higher in 34.4% vs 26.4%. Neutropenia in 41.4% vs 41.6%, and grade 3 or higher in 33.6% vs 30.4%.

Febrile neutropenia occurred in 2.3% vs 2.4%, all grade 3 or higher. Anemia in 37.5% vs 28.0%, and grade 3 or higher in 13.3% vs 15.2%. Hepatic toxicity was noted in 32.0% vs 20.0%, and grade 3 or higher in 8.6% vs 1.6%. Infections or infestations occurred in 41.4% vs 31.2%, and grade 3 or higher in 21.9% vs 9.6%.

Of note, patients with 1 or more AEs of COVID-19 occurred in 20.3% in the Pola-R-GemOx arm vs 13.6% in the R-GemoX arm. Matasar highlighted that this trial took place during the peak of the COVID-19 pandemic.

Reference

Matasar M. Polatuzumab vedotin, rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): results from the randomized phase III POLARGO trial. Presented at the 2025 European Hematology Association Congress, Milan, Italy. June 12-15, 2025.