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Published on November 3, 2020
Chronic Lymphocytic Leukemia Treatments and Combination Therapies
There are many available treatment paths for chronic lymphocytic leukemia (CLL), which can vary depending on health factors determined by you and your healthcare provider. We know that this can be an overwhelming landscape to navigate. Hear a doctor explain all of the current approved treatments and combination therapies for CLL, as well as the factors that go in to choosing one treatment path over another.
Patient Power Co-Founder and CLL patient advocate Andrew Schorr is joined by Dr. Brian Hill, Director of Lymphoid Malignancies at the Cleveland Clinic Taussig Cancer Institute, and Carol Preston, Online Host and CLL patient advocate, to take a deep dive into the current treatments and therapies available to CLL patients.
This series is sponsored by AbbVie Inc., Genentech Inc. and Adaptive Biotechnologies. These organizations have no editorial control. This series is produced by Patient Power, and Patient Power is solely responsible for program content.
Transcript | Approved Treatments and Combination Therapies for CLL
Andrew Schorr: So, we've got on the screen Dr. Hill, the inhibitors, inhibiting something about those B-cells.
What Are the Approved Treatments for CLL?
Dr. Hill: Yeah, so you're right. This slide shows four major categories, transplant sort of we can maybe save that for the end, but you have on the right there, traditional chemotherapy, we've mentioned a few of them like the bendamustine (Bendeka), fludarabine (Fludara), cyclophosphamide (Cytoxan). And then on the lower left, we have the antibodies rituximab (Rituxan) and obinutuzumab (Gazyva) and so forth. And then when I think of the inhibitors, what we have on this list are I think these are the five FDA approved. These are all pills; these are all oral medications that all block different signals or pathways within the CLL cell. So, the top two are sort of cousins. So ibrutinib (Imbruvica) and acalabrutinib (Calquence) sort of rhyme and these are both what we call BTK inhibitors. Happy to elaborate on that. The middle one there is a unique drug that targets something that prevents cells from going into cell death.
So, in other words, the CLL cells don't like to die and this venetoclax (Venclexta) tricks them into dying very quickly, which is a really neat way of targeting CLL. And then the bottom two duvelisib (Copiktra) and idelalisib (Zydelig), we'll probably not going to explore much today. There may be patients out there who are on these, what we've found with both of these is they're actually quite effective but they both also have a fair amount of side effects. And so, for that reason, they're not commonly used but I wouldn't rule out the possibility that there may be particular clinical scenarios in which they may be appropriate.
What Questions Should Patients Ask About BTK Inhibitors?
Carol Preston: So, you mentioned about elaborating perhaps just a bit on the BTK inhibitors because not necessarily all are equal. What questions should a patient ask and how do you help the patient decide?
Dr. Hill: Different treatments are required for different patients and different scenarios. So, what I usually start with is the age and sort of what we call in medical terms we call it performance status. So as long as you have a reasonably good performance status, you don't have major other medical problems, pretty much all of these options are on the table, but as you've alluded to more and more traditional chemotherapy is sort of being relegated. And the reason is that it actually doesn't work as well for high-risk CLL as the targeted drugs.
Do Oral Therapies Cover All Factors of CLL?
Andrew Schorr: These different drugs Doctor, depending upon these sorts of would have been traditional prognostic factors like Carol was alluding to what we've been told over the years was if you have this 17P deletion - not good news, unmutated not so good news, okay. With these oral therapies, do they cover that? In other words, moving away from chemo, whether we get the BTK or we get venetoclax, are they more or less like one-size-fits-all in that way?
Dr. Hill: It turns out that actually the newer drugs, the BTK inhibitors, the BCL-2 inhibitors, and the other two on there, which inhibits something called PI3-kinase, all of these work about as well in 17P deleted CLL or what we call intact so non-17P deleted. So that's why when you were thinking about treatment, you really want to make sure that you're not giving chemotherapy to someone who has a 17P deletion.
What Are the Differences Between Continuous and Fixed Duration Therapy?
Andrew Schorr: So you talked about the inhibitors. So, could you explain the choices between continuing to take pills like Christina from Oregon talked about in her video or having therapy for a while and being able to stop?
Dr. Hill: Yeah. So as great as the drugs are like for instance, the BTK inhibitors are very likely to work - over 80, 90% likely to work. And they will work to keep things under control many times for years and years and years. The difficulty is that they don't really eliminate the CLL to a deep remission. And so, you have to keep taking the pills. If you're not having side effects from the pills, and they're not costing you an arm and a leg every month, that may not be a problem. And some people are perfectly fine they take a blood pressure pill every day, they take maybe a cholesterol pill every day and they take a CLL pill every day.
For some people that's perfectly fine, other folks really have pre-sort of biases where they really don't want to be on medication for the rest of their life or for years, and years and years. And so, there are some targeted approaches that can be given just for, let's say, 12 or 24 months. And those are actually the regimens that use venetoclax. We talked a little bit about venetoclax in combination with antibody, and with this approach, we actually tend to get deeper remissions to the point where we can actually feel comfortable stopping treatment the same way we did after six months of chemotherapy, and we know now that the vast majority, probably 70 or 80% of people won't need to be treated for four or five years, at least with just continued observation.
Is Deep Remission Considered To Be a Cure?
So, if you open a textbook or get online and start reading about CLL, as many in your audience here today is probably done, the first thing that says is it's incurable. And what I would like to say about that is that it probably is curable in some people with very strong chemotherapies in the mutated IGHV status. We have now studies that show 10 or 15 years on that many people still don't need to be treated. So, that's basically a functional cure, but for the sort of high-risk disease, what I would say is it's not known to be curable in 2020, but I maintain that there may be people that we are going to find out in the next five years or 10 years, who are treated with some of these combinations to get very deep remissions and then go off treatment, and 10 years from now, are still not needing treatment. So, we need a time machine to find out the true answer to the question. I'm still working on that.
Carol Preston: I’m volunteering.
Dr. Hill: But yeah, I think that it's not implausible to think that we may be able to cure CLL with some of these combination treatments.
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