Hi, I’m Laurie Sehn from BC Cancer. And I’m here with my colleagues today, Doctor David Strauss from Memorial Sloan Kettering and Doctor Carmelo Carlo Stella from Humanitas University, Milano. And we’re here at the iwNHL meeting in Barcelona. And we just finished a really interesting session on novel therapies. We discussed several novel agents that have been recently developed, and, um, some of which have actually made their way to recent approvals based on exciting data. So we’re gonna just summarize a little bit about what we learned today. So, David, you presented exciting data on brentuximab vedotin and with some updated analysis that really has confirmed an overall survival benefit in patients.

Yes, it is really an honor to present this data, which is very exciting. Uh, brentuximab vedotin, uh, in two recent large randomized trials has shown a progression-free survival and also a survival advantage. One of these is CD30 positive peripheral T cell lymphoma, including ALK-related anaplastic large cell lymphoma, and the other is classical Hodgkin’s lymphoma. Uh, the data from the from the T cell lymphoma was recently updated at five years, and the survival advantage, uh, in the Hodgkin’s study was shown at six years. This is the first time in either disease that a randomized trial of a new regimen compared with standard of care has shown a survival advantage. I think it is, you know, remarkably impactful data.

So I have to say, in my own clinic, um, we’ve been presenting the data from the original study when there was a progression-free survival advantage and patients were generally presented with the option to, you know, adding the BV over the ABVD for Hodgkin lymphoma. But, you know, now, with the overall survival advantage, um, I’d say that, uh, it’s really been ingrained now is what we would consider to be a true new standard of care regimen for Hodgkin lymphoma.

Yes, I agree. I think that’s the gold standard. And even though the results in both arms were excellent, this is deaths and there was a 41% decrease in the risk of death from the BV plus AVD regimen as compared with ABVD standard, and it is impressive to think that that overall survival benefit has actually emerged quite quickly. I mean, we know that there are other novel therapies for Hodgkin lymphoma. And these patients, you know, certainly could have gone on to get other treatments with prolonged survival. So the fact that we are seeing that, uh and what I would consider still a relatively short time point is actually quite impressive.

I agree. Thank you. Um, there have been many trials, randomized trials through the years comparing standard of care with other regimens or modifications of them. Several of them have shown an advantage in progression-free survival. But this is the first time that one has shown a survival advantage. So I think it does really elevate this since you’re really talking about this and not just relapses, which might be effectively treated with other treatments. I think this does strengthen the case that it is certainly, I think, a preferred standard of care.

So, Carmelo, you presented data and another exciting antibody drug conjugate, which has recently received approvals in some jurisdictions, so loncastuximab tesirine. Why don’t you update us on that data?

Yes. I discussed the updated data of loncastuximab tesirine in diffuse large B cell lymphoma in the relapsed refractory setting. Uh, this setting is still an unmet medical need and loncastuximab was started being developed in this field a few years ago. The study I specifically discussed is the LOTIS-2 Phase II trial which led to the registration of loncastuximab by FDA. Uh, this study was performed in patients that were very high risk, with at least 60% of them being refractory to last treatment. And despite all loncastuximab showed the general activity in this, uh, heterogeneous patient population with 48% overall response rate and 25% complete response rate, the duration of response is substantial, more than one year in responding patients, this means that even if the curative potential of Lonca is limited But this the agent qualifies to be very promising, used in combination with other drugs for in the context of curative trials, testing novel combinations in this in this area that is now very rich and very attractive because of the diffuse number of different agents that are available and can be appropriately started.

So I think it is very important data and an important agent to see developed. You know, there’s this tendency because we’ve had several agents approved in the relapse refractory setting to try and compare data across trials. But certainly this trial had what I would consider to be a multiply treated patient population, Um, with most patients having had at least three lines of therapy and beyond. So I think it’s really difficult to compare across the different trials and,

you know, compare benefit. But clearly and and really, what was a highly treated patient group, I think the results are quite impressive, and as you said, it was a very well-tolerated drug. So we all have patients in our clinics. They’re not suitable for some of the other options. And it certainly is, you know, going to be a good thing to get our hands on, um, more tolerable options for these patients who inevitably, you know, need to go on two subsequent therapies along the way.

And one interesting aspect of this drug is that it’s very well tolerated in elderly patients. We made a comparison of toxicity in patients below 65 patient of both uh 65 up to 75 year old and long ago was always well tolerated in the very elderly patients so that now there is a randomized trial ongoing in diffuse large B cell lymphoma, non-transplant eligible patients. So essentially the role of patients are elderly above 70 and this is testing Lonca-T plus rituximab versus rituximab plus gemcitabine and oxaliplatinum.

And you know, So I think that there’s no question antibody drug conjugates have made their way firmly and established them as real options for non Hodgkin lymphoma. As part of the session, I also presented the POLARIX Trial, which explored the addition of polatuzumab vedotin, another antibody-drug conjugate in this case targeting CD79b as part of upfront therapy for diffuse large B cell lymphoma. So POLARIX was a large Phase III trial that compared head-to-head our current standard of care R-CHOP versus pola-R-CHP with the vincristine omitted to avoid again overlapping toxicity in patients with untreated DLBCL. And what that trial showed was that in a head-to-head comparison of over 400 patients in each arm, so a fairly large trial, the primary endpoint was significantly improved. That was progression free survival, with the addition of the polatuzumab. um And at the point of analysis, which had a medium follow up about 28 months, there was not yet an overall survival advantage. But patients receiving R-CHOP were much more likely to need to go on to secondary therapies, including stem cell transplant and CAR T cell therapy. So I think that that data certainly has served to, um, be quite compelling and that it’s the first randomized trial that we’ve had in diffuse large B cell lymphoma in untreated setting that’s actually met its primary endpoint. And it’s now emerging as a possible new standard of care for those patients. So we’re still waiting for, um, full approval in Canada. And I know it’s not yet been FDA approved, but it has been approved in the front-line setting by the EMA. And is that something that you have available in your own clinic now?

Yes. The EMA approved, uh, this combination a few months ago, and we have started using the combination in first line patients. We’re still discussing whether to use this combination in all the LBCL patients or whether to select uh, those, uh, that have some, uh, risk factors or, for example, to avoid the use of this combination in patients with early stage disease just to eliminate any risk of potential toxicity in in patients who don’t need to be any further addition to the conventional R-CHOP. But for sure, the combination is a significant advantage because after 20 or 30 years, we finally have a randomized study showing that there is a survival PFS advantage with an addition of a new agent to R-CHOP.

Yeah, it’s, you know, it’s been a challenge to make progress, and I think everybody’s excited to finally see a trial that really is showing an impactful difference.

Well, I think that it certainly was an exciting session. It’s been an excellent meeting so far. I thank you for your contribution and for enlightening us today. Um, and we certainly look forward to more exciting data emerging from all of these novel agents. That, I would say, is a really transforming patient outcomes in in real life. Thank you