Kerry Rogers, MD: I was really excited about something else that’s a huge deal I think, at this meeting, which is of course, the AMPLIFY study, which is a Phase III trial comparing chemoimmunotherapy with FCR or BR, compared to a fixed duration course of CALQUENCE® (acalabrutinib), and VENCLEXTA® (venetoclax)...or actually CALQUENCE® (acalabrutinib), VENCLEXTA® (venetoclax) and GAZYVA® (obinutuzumab).
Do either of you use chemoimmunotherapy in your regular practice? No. Same, I don’t do that either. I do think that’s a limitation of this study, that the comparator arm was chemoimmunotherapy. Of course it was not just done in the United States, which makes a difference. And this actually excluded patients with deletion 17p for that reason. But the abstract showed, unsurprisingly, that both the CALQUENCE® (acalabrutinib), VENCLEXTA® (venetoclax) and the CALQUENCE® (acalabrutinib), VENCLEXTA® (venetoclax), GAZYVA® (obinutuzumab) treatments were more effective. The progression free survival, which is how long people can expect to be alive and with their leukemia control, was better.
I guess, do you think…and especially, we can talk about with the antibody in a sec, but do you think that if CALQUENCE® (acalabrutinib) and VENCLEXTA® (venetoclax) is approved, that this might be useful or make it easier for some people to receive a fixed duration therapy? And who would you plan to use it for? I don’t know if you want to start, and then we can hear what Doctor Hampel has to say.
Catherine Coombs, MD: Yeah, I think I’m excited for the presentation because there are some things that we don’t quite know yet, and I’m interested to see, are there certain subgroups that may benefit more than others. What we’re not going to learn from this trial is, is it better than my standard of care, which is the VENCLEXTA® (venetoclax), GAZYVA® (obinutuzumab)? However, I think it does offer major convenience advantages. I think as long as the data look as good as I’m hoping, I would maybe pose both options, and for patients who are a bit overwhelmed by eight weeks of needing to be here in a row, the two drugs together I think is what appeals the most to me because it’s a lot easier to start on a pill that you don’t need this monitoring, and then do the monitoring that’s needed for the VENCLEXTA® (venetoclax) component.
I have a little bit of reservation about using all three drugs together. We’ve seen from not only this study, but also some other studies that you’ve been involved with quite a bit, that it adds a lot in the way of toxicity. And this study, especially because it enrolled patients at the height of the COVID pandemic, there were a lot more deaths from COVID and some say, “Oh, well, COVID’s ‘gone’.” But it could be something else. I think that the antibody does add in the way of infections. Those are things I’d be thinking about.
Kerry Rogers, MD: Yeah, I think you’re right. And even though we’re not currently having the same viral pandemic, that is still a very real risk to getting that. I think what you’re referring to is we have a Phase II study that was done at Ohio State with 75 patients, 50 of which were getting their first treatment that had IMBRUVICA® (ibrutinib), VENCLEXTA® (venetoclax), GAZYVA® (obinutuzumab) in a similar structure to this. The patients in that study were generally much younger and fit. The median age was 58, which we all know is young for CLL patients. That wasn’t by design, that’s who chose to enroll. But we do really see that…I think, especially in people who are older, it’s potentially a lot. More drugs is always more side effects, so I too am not sure exactly who would benefit from the three-drug combination.
But I think that the two drugs, certainly one of the major reasons that patients I see sometimes don’t want to do a fixed-duration first treatment is that it’s just a lot of work to do GAZYVA® (obinutuzumab) and VENCLEXTA® (venetoclax). So I’m hoping that the AB combination will make it easier for some of the patients to do that. And I’d like to hear…
Paul Hampel, MD: Yeah, I echo both of your thoughts. I’m more excited about adding a BTK and CALQUENCE® (acalabrutinib) and VENCLEXTA® (venetoclax) option into the toolbox when you’re discussing options, not necessarily saying this is supplanting all fixed-duration therapy, but another good option to choose from. I need to see more data for sure to best identify the patients who are going to benefit from the addition of the third drug where you know you’re getting more toxicity, infectious…generally speaking, not necessarily limited to COVID.
Kerry Rogers, MD: Well, plus, you haven’t made it that much more convenient if people have to come for the antibody infusions after all that anyway.
Paul Hampel, MD: If you’re doing the antibody infusions, then you have to be really convinced that it’s better than just doing VENCLEXTA® (venetoclax), GAZYVA® (obinutuzumab) because you are already committed with six months of GAZYVA® (obinutuzumab). You could just stop it a year if you added VENCLEXTA® (venetoclax), for many patients…would be very well served with that.
Kerry Rogers, MD: We’ve all used BTK inhibitor VENCLEXTA® (venetoclax) or BCL-2 inhibitor combinations investigationally, right? How does that generally go for your patients? For mine, usually it goes really well.
Catherine Coombs, MD: Yeah, mine too. And I think a lot of it is about patient selection, and so I am careful and cautious about which patient I put on which treatment because not everyone, I think, is going to tolerate it. And so I think the experience from the bigger study through the cooperative group, the ALLIANCE trial, where it was including older patients and many with a lot of other illnesses—that looked, I think, a bit worse than some of the smaller studies where maybe we’re cherry picking the really fit and healthy patients. But yeah, I had probably a good amount of patients on some of these larger studies. Mine actually did well but it doesn’t mean that that’s going to be the case for everyone. And so I think it’s important to consider what a patient comes with because CLL is generally a disease of older folks, often there are other illnesses, and that is part of, I think, this really nuanced discussion.
Kerry Rogers, MD: Oh, for sure. And there’s definitely some people where it is not good to…a BTK inhibitor would not have good side effects, like people with uncontrolled arrhythmias. I think we all have patients where BTK inhibitors even for a fixed duration would be something to avoid, like people with a pretty severe renal impairment, you’d want to avoid VENCLEXTA® (venetoclax).
Paul Hampel, MD: I think we, like you’re saying, have a decent amount of experience actually before the approvals, because combo BTKI and VENCLEXTA® (venetoclax) have been now explored with various agents. I think it is telling that we don’t have much experience off of studies, even with I plus V, despite the approvals elsewhere. Because frankly speaking, in the US, if you want to do those, we probably could have found a way to prescribe these off-label and get those if somebody really felt passionately that that’s what they wanted to do. So I think the difference here is you’re looking at something that likely will gain approval in the US with a different BTK inhibitor that, specifically speaking to the toxicity component, we’re perhaps more comfortable with, particularly in older patients compared to looking across the pond and GLOW study.
Kerry Rogers, MD: And I was really excited going back to that survey data, just to think that maybe this will be easier for patients and some of the community practices that aren’t as resourced, to offer a fixed duration option that’s more feasible or easier for everyone in that situation if appropriate. I think it’ll be interesting to see how that’s utilized. I’m excited about that.
