Triple combination of venetoclax-ibrutinib-obinutuzumab prolongs PFS compared to venetoclax-CD20-antibodies
27 Jun 2025
We presented at EHA 2025 our study titled POLARGO. This was a globally conducted randomised trial of R-GemOx versus R-GemOx plus polatuzumab vedotin in the treatment of patients with relapsed or refractory large cell lymphoma.
What was the study design?
After an initial safety run-in phase to confirm the tolerability of the combination of pola with R-GemOx, we then moved into a randomised trial, 1:1 randomisation, with 255 patients randomised. Eligibility criteria included relapsed or refractory large cell lymphoma, including transformed indolent lymphoma; one or more prior lines of therapy. Patients had to be both naïve to polatuzumab vedotin as well as be ineligible for stem cell transplantation.
What were the results of this study?
What we found was that the study was positive for our primary endpoint of overall survival, with a stratified hazard ratio of 0.6, which, of course, translates to a 40% lower risk of death. This was alongside improvements in quantitative overall survival, improving from 12 to 19 months for median OS. Improvements in median progression free survival, complete response rate and overall response rates were seen as well, with a doubling of CRR and a doubling of ORR seen with the addition of polatuzumab vedotin in these patients.
What is the clinical significance of these results?
I would say the clinical significance really references the role that polatuzumab vedotin can play in the management of relapsed refractory large cell lymphoma. Currently we do use pola-based treatment for patients in the second-line setting and beyond. The only approved combination to date has been in combination with bendamustine and rituximab. As we continue to learn about the deleterious downstream effects of the use of bendamustine, particularly as relates to negative impacts on subsequent T-cell engaging therapies, including CAR T-cell therapy, there has been a need for a better backbone, a better partner for polatuzumab that can drive response rates and outcomes without jeopardising subsequent decision-making.
The POLARGO regimen represents just such an advance and gives us, as oncologists, a new tool for leveraging polatuzumab vedotin in the treatment of relapsed large cell lymphoma without jeopardising outcomes from subsequent CAR T-cell therapy.
