Phase 3 POLARGO Trial Shows Survival Benefit of Polatuzumab-Based Regimen in R/R DLBCL: Matthew Matasar, MD

Following his plenary presentation at the 2025 European Hematology Association Congress this afternoon, Matthew Matasar, MD, chief of blood disorders at Rutgers Cancer Institute, further explores the findings of the phase 3 POLARGO trial (NCT04182204) in an interview with The American Journal of Managed Care^®.

The trial, outlined in the abstract he led titled, “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,” evaulated the efficacy and safety of polatuzumab vedotin in combination with rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) vs rituximab, gemcitabine, and oxaliplatin (R-GemOx) alone in transplant-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who had received at least 1 prior line of therapy.

This transcript was lightly edited; captions were auto-generated.

Transcript

For context, could you briefly describe the current treatment landscape for patients with relapsed or refractory DLBCL? Why is there such a pressing need for alternative options?

For treating patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible, or would not be expected to benefit from, stem cell transplantation, currently, it's a very fragmented therapeutic landscape, and there remains significant unmet need.

We have tools in this space, including antibody-drug conjugates, bispecific antibodies, and CAR [chimeric antigen receptor] T-cell therapy, but we need more options to be able to offer patients individualized treatment plans.

Given that background, what were the primary objectives of the phase 3 POLARGO trial? What methods did you use to evaluate them?

Polatuzumab's original approval in the relapsed or refractory [diffuse] large B-cell lymphoma setting was in combination with bendamustine and rituximab. We've since learned that using bendamustine in this context is disadvantageous, with deleterious effects on subsequent T-cell engaging therapies, like CAR T-cell therapy.

Additionally, BR [bendamustine and rituximab] as a backbone is perhaps not seen as a standard of care approach in the current era, and the benefit of polatuzumab added to a more typical platinum-based regimen was unclear.

This was what motivated the POLARGO trial, which was a globally-conducted randomized trial of such a regimen, R-GemOx [rituximab, gemcitabine, and oxaliplatin], with [Pola-R-GemOx] or without polatuzumab, to determine the incremental benefit of adding polatuzumab to a modern regimen.

Can you summarize the key findings? How did Pola-R-GemOX and R-GemOX compare in terms of both efficacy and safety?

Our key findings in terms of efficacy were that, indeed, we met our primary end point of overall survival improvement. We found a hazard ratio of 0.6, translating to a 40% lower risk of death among patients who were treated with the Pola-R-GemOx regimen compared [with the] standard of care. This was seen with improvements in both overall survival and progression-free survival.

Key secondary end points included complete response and overall response rates. We saw benefits across preplanned subgroup analyses, including, most notably, by cell of origin, with benefits seen in both the ABC [activated B-cell type DLBCL] and GCB [germinal center B-cell-like DLBCL] subtypes.

In terms of the safety profile, we did see an increased toxicity with the Pola-R-GemOx regimen, and this makes sense. Number one, it's 4 drugs vs 3. Number 2, there was much greater therapeutic exposure because the treatment was working, so patients were able to receive more rounds: a median of 7 and a half cycles of delivered therapy with Pola-R-GemOx vs a median of only 4 cycles with [the] standard of care, R-GemOx.

All that said, there were increased toxicities among patients treated with the Pola-R-GemOx regimen, including higher rates of peripheral neuropathy, infectious complications, and cytopenias.

Considering the global scope of this trial, how do you see access to Pola-R-GemOx evolving across different health care systems, particularly in settings with limited resources or access barriers?

It's an important question. Certainly, it was a globally conducted study, and it has a global impact. There's obviously a highly varied global landscape in terms of reimbursement for novel therapies.

What I would say is that these data are compelling and that the treatment program, in its ability to improve overall survival, really does move the needle in an important way. For countries that are already heavily using CAR T-cell therapy [and] bispecific therapy, the POLARGO program adds to an increasingly varied armamentarium in this context. For countries where reimbursement for CAR T or bispecific antibody [therapy] is more limited, polatuzumab-based treatment may be all the more attractive, and Pola-R-GemOx has the potential to be a new standard of care in such contexts.

What are the next steps for the clinical development of Pola-R-GemOX? Are there follow-up studies planned or underway?

Polatuzumab has been developed and already approved in other contexts, and this [the POLARGO trial] adds to our body of knowledge about how best to leverage this antibody-drug conjugate. We are planning additional correlative science on the specimens that we obtained during the conduct of POLARGO to better understand subset analyses and biological markers associated with [the] efficacy of this program.

Polatuzumab's development is ongoing. Certainly, there are ongoing clinical trials in the first-line setting, leveraging the POLARIS backbone of R-CHP [rituximab plus cyclophosphamide, doxorubicin, and prednisone] plus polatuzumab, with [the] addition of other novel therapies in the first-line setting to continue to try to improve upon our ability to cure this disease.