Published on November 13, 2020
How Do You Decide Between Treatment Options for CLL?
CLL patients have more treatments available than ever before, but with lots of choices come lots of decisions. Often, this decision is between fixed duration treatments like obinutuzumab (Gazyva) and venetoclax (Venclexta), indefinite treatments like BTK Inhibitors, imbrutinib (Imbruvica), or acalabrutinib (Calquence).
Dr. Jeff Sharman Medical Oncologist, Willamette Valley Cancer Institute and Research Center; Medical Director, The US Oncology Network and Patient Power Co-Founder and CLL Patient, Andrew Schorr, discuss the different approaches to CLL treatment and their advice on medical decision making.
Transcript | Advice on Medical Decision Making for CLL Treatment
Andrew Schorr: Hello, and welcome to Patient Power. I'm Andrew Schorr. We're with our regular guest, CLL expert, Dr. Jeff Sharman, who joins us from Eugene, Oregon. Dr. Sharman is a Medical Director with the US Oncology Network and he's Medical Oncologist at the Willamette Valley Cancer Institute and Research Center. Jeff, thanks for being with us once again.
Dr. Sharman: Thanks Andrew. It's nice to be here.
Andrew Schorr: So, for people like me, living with CLL, we have more choices than ever. We have a variety of oral medicines. We have some infused medicines that go with it. How do you discuss with your patients what some of the choices are?
Dr. Sharman: One of the, I think, hardest things about being a patient, is being presented with a choice. Most of the time with CLL, you don't have to make instantaneous decisions. You actually have some time to consider your options. That's both good and bad.
The good is that you have time. The bad is that time really can create anxiety, if you feel like somehow, you're going to make a bad choice. The good thing in CLL, really Andrew, is that we have many good options to choose from.
What are the Similarities and Differences Between Treatment Options?
Andrew Schorr: So, Dr. Sharman, let's go through this. On the one hand, you have a group of medicines known as BTK inhibitors?
Dr. Sharman: Right.
Andrew Schorr: Bruton tyrosine kinase inhibitors approved right now are Imbruvica and Calquence or ibrutinib and acalabrutinib, the generic names, which would be in this category where you keep taking them. And of course, there's the medicine, maybe some side-effects or not, and some expense, depending upon your insurance.
The other way you could go, is you could have an infused therapy for some fixed time. Typically, obinutuzumab, trade name, Gazyva, with venetoclax, trade name, Venclexta. And you might be able to stop at a point of time, one year, two years down the road and be monitored.
Dr. Sharman: Yeah, those are the choice for most patients, and something at least worthwhile considering, is what is the role of chemotherapy in the frontline setting? I will tell you that is controversial in the field, not a slam dunk-answer.
Andrew Schorr: So how would you coach people to have a discussion with their doctor so that these options, all of them, are put on the table and they can evaluate them with their doctor?
Dr. Sharman: Number one is that I think many providers out there are unfamiliar with molecular tests and that's a problem because they're underutilized. And I think for doctors who are unfamiliar with them, they're even sometimes dismissed.
If a doc says, "Oh, don't worry about those," I think maybe you say, "It's important for me, I would like to know." If we just make this simple for the time being about the obinutuzumab-venetoclax versus BTK inhibitors, you know, I think you talk with your doc about, "Do I want fixed duration therapy that is more intensive on the front end, but gives me a drug-free experience on the backend?" Or “Am I comfortable just taking an indefinite therapy because it doesn’t really bother me doing so?”
How Do Indefinite and Fixed Duration Therapies Compare?
Andrew Schorr: Just so people understand one is ongoing pills and depending upon your insurance or assistance, maybe ongoing expense. The other, what you are referring to, is fixed duration therapy, which may be front-end loaded with more trips to the clinic and more monitoring. But the hope is, maybe you could stop everything. If somebody is able to stop, then what's your experience now with that obinutuzumab-venetoclax experience? How long do people get to be off all therapy or do we even know?
Dr. Sharman: We don't actually know yet. We don't have what we call a median. A median is a statistical term for an approximation of how long patients oftentimes get. It's that halfway point where half of patients are still in remission, and half of patients have progressed. As we're getting longer and longer-term follow-up, we're getting closer and closer to a median. But in that therapy, if you get through the therapy and do well, one year of therapy, it's looking to me like maybe between four to five years, total duration of median progression-free survival is a rough estimate. And we know very little about retreatment with that regimen. So, if somebody got a longer remission you could even consider repeating that down the road if you needed to – information we just don’t have right now.
Andrew Schorr: Dr. Sharman, we've talked about different directions people could go, when they need treatment. So, one was with the BTK Inhibitors, another was with the obinutuzumab and venetoclax. Could somebody switch along the way? If you decide to go left, but maybe there's side-effects or whatever, could you go right?
Dr. Sharman: For patients who start with obinutuzumab-venetoclax, most patients are going to have time where they don't have active disease. And I wouldn't switch to a new therapy just because they had to stop obinutuzumab-venetoclax. I'd wait until they actually need therapy again, because that could be some length of time.
We've studied obinutuzumab monotherapy, we've studied it in combination with venetoclax. Patients are going to get disease free time, no need to jump right away. The expectation is yes, once those patients progress, they very likely would go on to a BTK inhibitor. Again, I bring up the point that we don't totally know about retreatment yet. Maybe you just stick with the same therapy again, if you get multiple years out of it.
In the other direction, we know that venetoclax works really well after BTK inhibitors. Now, in contrast, with BTK inhibitors, the question is, "Why did you stop?" If you stopped for side-effects and so forth, if your disease was well controlled at that point, we know from some studies that disease will continue to be controlled oftentimes for a length of time, year, two years or so. And so, for those patients, I wouldn't jump right into venetoclax just because you had to stop for side-effects.
On the other hand, a patient who is experiencing disease progression on a BTK inhibitor, those are patients who can get quite sick, quite quickly. And I actually, in some cases, will even overlap the new therapy with the old one. It depends a little bit upon the circumstances as to how you would jump. But I wouldn't make the assumption that you just switch because, "Hey, I don't like this one," or "This doesn't seem right to me." There's a little bit more thought that goes into it than that.
Andrew Schorr: The good news is we have more options than ever before. Clinical trials are going on to see if various combination therapies would have a bigger bang. So, the option for a CLL patient to live longer and live better is greater than ever before, it would seem.
Dr. Sharman: Most patients are going to outlive their CLL. I think we're getting closer and closer to being able to cure this disease with more regularity and I think that's going to be coming soon.
Andrew Schorr: That is all great news, Dr. Jeff Sharman, thank you for explaining this to us and for your devotion to research and patient care. Thanks for being with us once again.
Dr. Sharman: Happy to be here, Andrew. Thank you.
Andrew Schorr: I'm Andrew Schorr with Dr. Jeff Sharman from Oregon. Remember knowledge can be the best medicine of all.
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