番茄社区

, patients with diffuse large B-cell lymphoma (DLBCL) had a significantly higher likelihood of survival without disease progression 2 years after receiving a new drug combination known as pola-R-CHP (polatuzumab vedotin [Polivy] with rituximab, cyclophosphamide, doxorubicin, and prednisone) compared with those who received the standard of care.

The findings, presented at this month's American Society of Hematology (ASH) virtual meeting, represent the first regimen in 20 years to improve progression-free survival in DLBCL versus the standard of care, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

番茄社区 brought together three expert leaders in the field: Moderator , is joined by , and , for a virtual roundtable discussion. This first of four exclusive episodes focuses on the positive results found in the phase III POLARIX study.

Following is a transcript of their remarks:

Flinn: Hello, I'm Ian Flinn from the Sarah Cannon Research Institute in Nashville, Tennessee. I'm joined today by Loretta Nastoupil from the MD Anderson Cancer Center and Amit Mehta from University of Alabama at Birmingham. We're gonna talk about some of the exciting news that's come out of ASH 2021.

It was a big year for lymphoma studies this year. And I think we have a great discussion. So, Amit maybe we could talk first about the POLARIX trial. This was this large international randomized phase III trial, trying to use the polatuzumab vedotin with R-CHP regimen compared to R-CHOP. It was some exciting results. I think for the first time in the frontline treatment of large cell lymphoma, we're seeing a trial that has a positive outcome. Can you walk us through that trial and give us a few comments on it?

Mehta: Sure. As you said, there was a lot of excitement about the POLARIX study. So the POLARIX study is a phase III, double-blind, randomized study where R-CHOP was compared with R-CHP polatuzumab. And it was a large international study where patients with newly diagnosed diffuse large B-cell lymphoma, with high risk IPI [International Prognostic Index] were randomized between these two arms. Important to mention that in both arms the patient received an extra two doses of rituximab.

The primary endpoint of the study was the investigator-assessed progression-free survival. And if you look at the data, the study did meet the primary endpoint. The investigator-assessed progression-free survival was better in the experimental arm, which is the R-CHP-pola arm compared to the R-CHOP arm.

So yes, you can say that after a long time, we have seen that the needle is moved in the right direction, so a positive study for the frontline diffuse large B-cell lymphoma setting. Also, of course the follow was shorter, but overall survival, there is no difference between those two arms. Importantly, the toxicity profile was similar in both the experimental arm as well as the R-CHOP arm.

Flinn: Loretta, I think if it was about a six and half percent difference, if I remember correctly, the progression-free survival between these two arms, and there's not an overall survival advantage. But what is your take, is this gonna be the new standard? Is this what we're going to be doing in 2022?

Nastoupil: Yeah, I think the takeaway from the study for me is we finally have a positive study, and that's after many, many years of trying. So what was different about this trial versus all the other attempts? I think what they did right is they made it easy for folks to qualify for this study. And all we had to determine was IPI. And having an IPI of two or higher, and obviously meeting all the other eligibility criteria, that's so much simpler than trying to define the molecular subtypes. Though that may be more attractive from a scientific and a molecularly targeting study, I think this is a really simple study. We replace vincristine, which is the least effective in my opinion of the CHOP backbone, with a targeted therapy. And it results in improvement.

Now to be critical, the safety profile wasn't better. And yes, it was a modest improvement in PFS and EFS with no overall survival advantage. But when I'm in clinic, and this is approved, if I have a young, fit patient with an IPI of three or higher, it's gonna be hard for me to forgo this option knowing how hard it was to finally get to a positive study.

Flinn: I guess I have a very similar take to you. I mean, we know we don't have, as yet, an overall survival advantage, but at six and a half difference in progression-free survival, to an individual person that's a big deal. And so I guess we'll look more to get this drug approved, hopefully in this coming year.

Watch Episode 2: Is Second-Line Axi-Cel the New Standard in Aggressive B-Cell Lymphoma?

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