Novel Treatment Combinations for R/R DLBCL

Brian Hill, MD, PhD: The POLARGO study, as it’s called, is a large, global phase 3 trial that compares a standard chemotherapy regimen, R-GemOx, which is rituximab, gemcitabine, oxaliplatin. And the comparator arm is rituximab, gemcitabine, oxaliplatin with polatuzumab vedotin, which is an antibody-drug conjugate now approved for diffuse large B-cell lymphoma.

The purpose of this study is to demonstrate or test whether the introduction of this antibody-drug conjugate improves the outcome of patients with diffuse large B-cell lymphoma treated with rituximab, gemcitabine, oxaliplatin in the relapsed/refractory setting. This trial is ongoing, but I think there’s a fair amount of optimism that we may see a positive result here, which would improve or expand the number of treatment options for patients with relapsed or refractory diffuse large B-cell lymphoma.

Andre Goy, MD: I think you’re referring to the LYSA trial presented at ASCO [the American Society of Clinical Oncology annual meeting], which was atezolizumab, a checkpoint inhibitor, with obinutuzumab and venetoclax in relapsed/refractory large cell lymphoma. This was a small number of patients.

I think 80%-plus of patients had at least 2 lines of therapy, and two-thirds of them were refractory to the last regimen. I don’t remember the exact number of patients, but the trial was reported with an overall metabolic response at the end of treatment of 24%, and an 18% complete metabolic response. It’s early for the follow-up, but this is again one of these combinations, a biological agent plus immunotherapy. That might bring an opportunity to the unmet need of patients who are not eligible for high-dose therapy, transplant, or potentially CAR [chimeric antigen receptor] T-cell therapy. It’s another example of the impact of immunotherapy as well.

I would like to summarize and say that this is a very exciting time in the field of medicine, particularly in lymphoma where we have been, for decades, doing R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], which remained as the standard of care default. But we definitely should be aware that this is not sufficient in a high-risk IPI [International Prognostic Index] patient, double hit, double expresser, and non-GC [germinal center] subtype, and other high-grade lymphoma that I alluded to previously. And I think that these patients should be recommended for clinical trials and probably more intensive therapy and maybe cell therapy consolidation, like the ZUMA-6 trial looking at CAR [chimeric antigen receptor] T-cell therapy as consolidation in patients who have double-hit lymphoma, high-grade lymphomas.

It is really not altered, but probably underestimated. But the future is the biological classification of lymphoma and trying to improve this curve that we see, to identify truly the high grade. And to do this, we need to have a baseline signature that is usable in routine and actionable. I think cell-free DNA, or circulating tumor DNA, is likely to be more usable and used in the future. As I mentioned, immunotherapy is more and more part of the induction or pre-phase consolidation. And again, given all the opportunities that I just mentioned tonight, it reflects on the fact that it is really important to encourage physicians to go to clinical trials, to participate. The reason being is that when you look, the impression is that large cell lymphoma now is a clinical result, the outcome is so great. But when you look at real-world data in high-risk patients, the outcome particularly in a high-risk patient is still very poor. So I would encourage physicians to look at clinical trials in this population as well. Thank you.

Transcript edited for clarity.