EHA 2025 | Results from the Phase III POLARGO trial: Pola-R-GemOx vs R-GemOx for R/R DLBCL

My name is Dr Matt Matasar. I’m the Chief of Blood Disorders at the Rutgers Cancer Institute, and on behalf of my colleagues, pleased to share the results of our trial entitled Polatuzumab vedotin, Rituximab, Gemcitabine, and Oxaliplatin, or PolaR-GemOx, or POLARGO, for relapsed or refractory large cell lymphoma. Disclaimer here, followed by my personal disclosures. 

Polatuzumab vedotin is an antibody drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B-cells. This drug delivers a payload called MMAE, which induces cytotoxicity via microtubule disruption. It’s been previously evaluated and approved in combination treatments in the management of diffuse large B-cell lymphoma, both in the relapsed or refractory setting combined with bendamustine and rituximab, as well as in the first-line context, combined with the R-CHP platform, the trial known as POLARIX. Here we present the results from a randomized Phase III trial comparing R-GemOx with or without polatuzumab in the treatment of patients with relapsed or refractory large-cell lymphoma who were otherwise deemed transplant ineligible. 

Shown here is the trial schema of the POLARGO trial. This is a Phase III randomized trial. After completing a safety run-in, patients with relapsed or refractory large cell lymphoma, either de novo or transformed indolent disease, having received one or more prior lines of therapy and deemed transplant ineligible, were randomized to either receive standard of care R-GemOx or R-GemOx plus polatuzumab. The primary endpoint was overall survival with key secondary endpoints, including PFS, complete response, and overall response rates. 

Shown here are the overall survival primary endpoint results. And you see here that we did indeed lead to a statistically and clinically meaningful survival benefit with the POLARGO regimen compared to standard of care R-GemOx with a stratified hazard ratio of 0.6, resulting in a 40% overall reduction in the risk of death with the use of polatuzumab plus R-GemOx compared to R-GemOx alone. Median overall survival was improved from 12.5 months to 19.5 months. And the likelihood of being alive at two years, the 24-month event-free rate, was 44% in the experimental arm compared with 33% in the control arm. 

We improved our key secondary endpoints as well, including progression-free survival shown on the left here with a stratified hazard ratio of 0.37. And on the right, you see that there are improvements in overall response rate, a doubling of overall response, largely driven by a doubling in complete response from 19% to 40% with addition of polatuzumab vedotin. 

Summarized here are our safety results, and indeed, it is important to recognize that because there were differences in therapeutic exposure between the two arms, 7.5 cycles of median therapy with the experimental treatment compared to only four cycles with standard of care, with increased exposure is likely to come increased in treatment-related adverse events, and this was seen. There was furthermore an increase in grade five adverse events with 11.7%, the minority of which were deemed treatment-related. The most common cause of a fatal adverse event was infection, and the most common infection leading to death was COVID-19. Please note that this trial was conducted during a period of time that was considered peak COVID. As two of the constituent components in the POLARGO regimen are associated with neurotoxicity, we looked carefully at neuropathy. Neuropathy was increased along with the increased exposure to therapy, but these were largely low-grade in severity, and some patients who experienced neuropathy had improvement at the time of study completion. 

In summary, we feel that the POLARGO data defined a new and meaningful improvement in the treatment of patients with relapsed or refractory large cell lymphoma, with a 40% reduction in the risk of death compared to a standard chemotherapy program of R-GemOx. This was achieved with an improvement of approximately seven months in overall survival. Improvements in progression-free survival, complete response rate, and overall response rate were all consistent. We saw that the toxicity was consistent with the toxicities of the individual components. And in summary, we feel that these data really do represent a new opportunity for the treatment of patients with relapsed or refractory large cell lymphoma, both adding to our overall understanding of the rationale and role for its use in combination with chemotherapy programs, as well as giving us a new tool in the treatment of patients with relapsed or refractory large cell lymphoma.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.