Full POLARGO Data Reveal OS, Safety for Pola-R-GemOx in DLBCL

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who cannot undergo a stem cell transplant have had limited options once initial treatment fails. Median overall survival (OS) reached 19.5 months with polatuzumab vedotin added to rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx), compared with 12.5 months for rituximab plus gemcitabine and oxaliplatin (R-GemOx), according to final results of the phase 3, randomized POLARGO trial published in the Journal of Clinical Oncology.¹

An Unmet Need in Transplant-Ineligible DLBCL

Despite progress in first-line treatment of DLBCL, patients whose disease relapses or proves refractory continue to face a poor prognosis. High-dose chemotherapy with autologous stem cell transplant was historically standard in the relapsed setting, but many are ineligible because of age, comorbidities, or inadequate response to salvage therapy. Chimeric antigen receptor (CAR) T-cell therapy has since displaced transplant for many, though cost and access can limit use. Polatuzumab vedotin, an antibody-drug conjugate approved in first-line DLBCL, had shown benefit paired with bendamustine and rituximab in the relapsed setting. POLARGO tested whether pairing it with gemcitabine and oxaliplatin could expand options for transplant-ineligible patients.

This is not the first look at POLARGO. A presentation of the trial at the European Hematology Association's 2025 congress prompted earlier coverage citing a hazard ratio (HR) of 0.6 for OS, a 40% reduction in the risk of death with Pola-R-GemOx.² That presentation lacked the median OS, progression-free survival (PFS), and safety figures now available in the peer-reviewed publication, offering a fuller picture than the conference talk could.

POLARGO (NCT04182204) was a multicenter, open-label, phase 3 trial at 64 sites in 16 countries.¹ After a safety run-in of 15 patients, investigators randomly assigned 255 adults with transplant-ineligible R/R DLBCL, not otherwise specified or transformed from indolent lymphoma, 1:1 to Pola-R-GemOx (n = 129) or R-GemOx (n = 126) every 21 days for up to 8 cycles. All had received at least 1 prior line of therapy, with randomization stratified by age, prior lines, and refractory status.

Median age was 65 years (range, 20-89); most patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 (88.2%) and stage III/IV disease (76.5%). Nearly two-thirds had received only 1 prior line of therapy, and 65.9% had disease refractory to their most recent treatment. The primary end point was OS. The key secondary end points included PFS and independently assessed complete response (CR) and overall response rates (ORR) at the end of treatment.

Survival and Response Benefits With Pola-R-GemOx

After a median follow-up of 24.6 months, Pola-R-GemOx reduced the risk of death by 40% relative to R-GemOx (HR, 0.60; 95% CI, 0.43-0.83; P = .0017), meeting the primary end point. Median OS reached 19.5 months (95% CI, 13.3-not estimable) vs 12.5 months (95% CI, 8.9-15.8) with R-GemOx, and the 24-month OS rate was 44.0% vs 33.2%.

Secondary end points also favored the 4-drug regimen. The risk of progression or death fell 63% (HR, 0.37; 95% CI, 0.27-0.51; P < .0001), with median PFS of 7.4 vs 2.7 months. The CR rate more than doubled, from 19.0% to 40.3%, and ORR rose from 24.6% to 52.7%. The survival advantage held across subgroups, including activated B-cell-like and germinal center B-cell-like disease.

"The POLARGO study establishes Pola-R-GemOx as an effective and tolerable treatment option for patients with transplant-ineligible R/R DLBCL, significantly improving OS and CR rates and representing a valuable, non-lymphodepleting addition to the current therapeutic landscape," the authors wrote.

Safety and Tolerability

The most common grade 3/4 adverse events in both arms were thrombocytopenia and neutropenia. Peripheral neuropathy occurred more often with Pola-R-GemOx, affecting 57.0% of patients vs 28.8% with R-GemOx, though most cases were grade 1, and only 2.3% discontinued polatuzumab vedotin because of it. The dose intensity of the GemOx backbone was preserved despite the added agent.

Fatal adverse events were more frequent with Pola-R-GemOx, occurring in 12% of patients vs 4% with R-GemOx, driven largely by infections, including COVID-19 (5.5% of fatal events vs 1.6%). Discontinuation because of toxicity was also more common with the 4-drug regimen (23.4%) than with R-GemOx (8.0%), most often from infection or thrombocytopenia.

Limitations and Clinical Implications

The authors noted that POLARGO was designed before CAR T-cell therapy was approved for second-line use and before polatuzumab vedotin entered first-line treatment, so the trial cannot address how Pola-R-GemOx performs in patients already exposed to the agent earlier in care. They also acknowledged that R-GemOx, the comparator arm, is increasingly viewed as an outdated standard and that differing baseline characteristics across trials of similar regimens limit cross-trial comparisons.

Even with those caveats, the mature survival data mark an advance over what was available when the trial was first presented without median OS or safety figures. For clinicians weighing bridging therapy before potentially curative cellular therapy, and for payers evaluating a 4-drug regimen against newer bispecific combinations, the data now offer a fuller basis for decision-making in a population that has long lacked durable options.

References

1. Matasar M, Li Z, Vassilakopoulos TP, et al. Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial. J Clin Oncol. 2026;44(25):2435-2446. doi:10.1200/JCO-25-02849
2. McCormick B, Matasar M. Phase 3 POLARGO trial shows survival benefit of polatuzumab-based regimen in R/R DLBCL: Matthew Matasar, MD. AJMC^®️. Published June 14, 2025. Accessed October 8, 2026. https://www.ajmc.com/view/phase-3-polargo-trial-shows-survival-benefit-of-polatuzumab-based-regimen-in-r-r-dlbcl-matthew-matasar-md