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Pola-R-GemOx Boosts Survival in R/R DLBCL
MILAN — Combining polatuzumab vedotin (Pola) with rituximab, gemcitabine, and oxaliplatin (R-GemOx) significantly improves survival outcomes in patients with transplant-ineligible, relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), according to new data from the phase 3 POLARGO trial.
Presented by Matthew Matasar, MD, chief of the division of blood disorders at Rutgers Cancer Institute, New Brunswick, New Jersey, here at the European Hematology Association (EHA) 2025 Annual Meeting, the study showed a 40% reduction in the relative risk of death with Pola-R-GemOx versus R-GemOx alone. "These are the gems of the congress," said Martin Dreyling, MD, scientific program committee chair for EHA2025, who presided over the session, describing this and similar studies as potentially practice-changing.
Improved OS and PFS
Matthew Matasar, MD
The global trial enrolled 270 patients with R/R DLBCL who were ineligible for autologous stem cell transplant, had received at least one prior line of therapy, and had not previously been treated with Pola. Of those, 255 were randomized 1:1 to receive Pola-R-GemOx or R-GemOx every 21 days for up to 8 cycles. Patients were stratified by age (≤70 vs >70 years), prior lines of therapy (1 vs ≥2), and response to the most recent treatment (relapsed vs refractory). Baseline characteristics were well-balanced between groups; two thirds were treated in the second-line setting and most had refractory disease.
At a median follow-up of 24.6 months, the primary endpoint was met: median overall survival (OS) was 19.5 months with Pola-R-GemOx versus 12.5 months with R-GemOx (hazard ratio [HR], 0.60; 95% CI, 0.43-0.83; P = .0017). Two-year OS was 44.0% versus 33.2%, respectively.
Progression-free survival (PFS) also significantly improved at a median follow-up of 18.7 months (HR, 0.37; 95% CI, 0.27-0.51; P = .0001), increasing from 2.7 months to 7.4 months. The 12-month PFS was 36.6% for Pola-R-GemOx and 17.9% for R-GemOx.
Response rates were nearly double in the experimental group. The overall response rate (ORR) was 52.7% versus 24.6% and the complete response rate was 40.3% versus 19.0%, respectively, as assessed by an independent review committee.
Subgroup and Safety Analyses
The OS benefit was consistent across subgroups, including those with and without bulky disease, and among both primary refractory and non-refractory patients. Notably, survival benefit was seen in both activated B-cell (ABC) and germinal center B-cell (GCB) subtypes — contrary to prior findings from the POLARIX trial, which had suggested preferential benefit in the ABC subtype.
Matasar emphasized the robustness of the results, noting that patients receiving R-GemOx underwent more subsequent lines of therapy, ruling out confounding by post-progression treatment access.
However, the enhanced efficacy came with increased toxicity. Patients in the Pola-R-GemOx group received a median of 7.5 cycles versus 4 cycles in the R-GemOx group. Treatment discontinuations due to adverse events (AEs) were more common with Pola-R-GemOx (23.4% vs 8.0%). Grade 3-4 AE rates were similar (57.0% vs 58.4%), though thrombocytopenia and infections were more frequent in the experimental group. Infections were the leading cause of grade 5 AEs, including 10 COVID-related deaths (seven during treatment, three after completion). "It's worth remembering that the study was conducted during the peak of the COVID-19 pandemic," Matasar noted.
Peripheral neuropathy, an expected AE due to overlapping neurotoxicities of Pola and oxaliplatin, was observed in 57.0% of patients receiving Pola-R-GemOx versus 28.8% with R-GemOx. Most cases were grade 1, but 3.9% of patients in the experimental group had grade 3 events. "Peripheral neuropathy was not permanent in all patients, approximately half of the patients did experience improvement in neuropathy by the time of study closure, and approximately one third of patients had complete resolution," Matasar reported.
A Role in Bridging Therapy?
Frank Leebeek, MD, PhD
Commenting to Medscape Medical News, Frank Leebeek, MD, PhD, chair of hematology at Erasmus University, Rotterdam, Netherlands, who was not involved in the trial, said: "This is very important. Prognosis remains poor for patients with R/R DLBCL who cannot receive or are ineligible for transplant." He welcomed the new option in the arsenal of treatments for this disease.
Concluding his presentation, Matasar stressed the importance of having different tools. "Some patients will be appropriate for CAR-T, some for bispecific antibodies, some will have access to neither and benefit from ADC destination therapy. Pola-R-GemOx represents an alternative treatment option," he said.
Leebeek noted that Pola-R-GemOx may serve as a bridge therapy to CAR-T because it does not deplete the T-cell population. "Achieving complete remission after relapse is challenging," he said, "and other regimens can impair the T-cell pool, while this one doesn't."
The study was funded by F. Hoffmann-La Roche. Matasar has disclosed financial relationships with ADC Therapeutics, AbbVie, Arvinas, AstraZeneca, Bayer, BMS, Genmab, Ipsen, J&J, Kite, Novartis, Regeneron, Roche, and Pfizer, and research support from Allogene, Arvinas, Bayer, Cellectis, Genentech, J&J, Pfizer, Pharmacyclics, Regeneron, and Roche. He has reported serving as a consultant for AbbVie, Allogene, Arvinas, Bayer, BMS, Genentech, Genmab, Kite, Novartis, Pfizer, and Roche, and being a current equity holder of Merck. Leebeek has reported no relevant financial relationships.
