EHA 2025 | Fixed-duration versus continuous treatment of venetoclax-based regimens in CLL

So I like the data that was shown at EHA in the sense that we have the FLAIR update that showed that there was superiority in the group that received ibrutinib plus ven when compared to FCR or ibrutinib. The ibrutinib and combination reduce the risk of progression of death by 87% compared to FCR. Again, you know, we had that data from the E1912 that was done in the United States. Even though this study was done later on, it’s interesting to see that this study was done when there were other drugs that were available. Like when we did E1912, venetoclax was not yet approved. And so there was a survival advantage, whereas with the FLAIR, venetoclax was already approved and it could have been used as a salvage therapy. That’s one of the studies that was presented. The other study that was presented was the CAPTIVATE to longer follow up. The combination showed that, you know, like the five year PFS estimates are still really high. And the CLL13 analysis was also presented showing that the combination of ibrutinib with obinutuzumab and venetoclax also showed excellent five-year PFS estimates. The concern is that for those patients with unmutated disease or TP53 mutation, these patients tend to continue to show earlier relapses compared to everyone else. and I don’t want to forget ATM deletion or 11q deletion. That also correlates with a shorter remission duration and like fixed duration treatment strategies. So we still have that concern, but again, like these are fixed duration treatment strategies so the patients are able to live a life without any therapy for years, right, on average. So whether I would be willing and comfortable to be challenging with the same regimen, it’s, you know, we have now data that, yes, it’s possible, and many of the patients do respond well. Dr Matt Davis presented data on the REVENGE trial where patients are exposed, again, to venetoclax, and you can retreat. So one question that I always get asked is, do you do fixed duration treatment strategy or do you re-challenge with like single agent and then you can do continuous daily dosing? And I think at this moment, it really depends on the patient. For example, I have a patient that was on the Captivate 2 trial and he’s starting to show some, he’s young, he’s only 40, and he started to show some signs of progression. He’s not there yet to be started on therapy, but when asked, he’s like, listen, I don’t want to change my life. I still want to do like a fixed duration treatment strategy. But for someone that is older, I would probably be more inclined to just give them a continuous therapy. So I think the field is evolving because we still, all these mature data are just appearing and we’re trying to make sense of how we best and optimize the therapies for our patients. I think that fixed duration treatment strategy is the way to go moving forward for patients that are young and healthy and fit and are willing to do a little bit of more intense monitoring at the beginning of the study or the regimen because they might develop TLS or other toxicities. Now, I’m not convinced at this moment based on the data that I’ve seen that the addition of obinutuzumab should be done on everyone because of the concern for more potential toxicities, including infection risk. And that has been seen with patients that were treated during the era of COVID and many of them did not have a good outcome. And not only infections, like it can also cause more toxicities in terms of like thrombocytopenias or prolonged immunosuppression. So I’m still not embracing the triple therapy regimen, but it looks amazing. It’s just that it comes at an added cost and many of our patients you know like even on that data that we presented most of our patients are in their late 60s 70s still. We do have some younger people but it’s the minority and so for a young patient yeah absolutely no questions asked. But for an older patient that just you know like they’re used to also taking a pill for the blood pressure or diabetes, I wouldn’t push for anything too aggressive because achieving a deeper MRD might be good in paper, but it comes at a cost.

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