Understanding CLL Treatment Resistance and Next Steps

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Topics include: Treatments

Chronic lymphocytic leukemia (CLL) patients on newer, oral therapies want to know how long treatment will last. What happens if cancer cells start to resist the effects of treatment? What conversations should patients have with their care team about next steps? Watch as leading CLL expert Dr. David Maloney, from the Seattle Cancer Care Alliance, discusses the capabilities of novel agents, response duration and other options if patients develop treatment resistance.

This program is produced by Patient Power. It is sponsored through a grant from Janssen Oncology and Pharmacyclics LLC. These organizations have no editorial control.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

What do we do about it, and what should patients, what dialogue should patients have with their doctors about it?  So here's Dr. David Maloney from the Fred Hutchinson Cancer Research Center who has been looking at that and what he has to say.  

And in contrast, though, if you take patients before they ever get treated with any chemotherapy, ibrutinib seems to work longer.  It seems to lead to a potentially longer duration of response.  Ibrutinib is really a tremendous drug.  The problem is it doesn't probably cure anybody.  It's just kind of a stabilization, and it causes—it's a tremendously great drug but it still—it doesn't eradicate CLL.  

And I think the exciting area is that combination therapy with ibrutinib and then this new Bcl-2 drug like venetoclax (Venclexta) and then combining that with an antibody, now we may be able to be getting to the situation where we can get people actually into deep remissions and be able to stop their therapy.  

So I think for now, no one should be clamoring for CAR-T cells in the early stage of their disease.  They should be getting our best available therapy, which is usually with a BTK inhibitor, one of several different types, either on clinical trials or combinations with agents such as venetoclax or an antibody and try to use that as long as it's going to last.  And I think the earlier—when those things are used in patients before now they get exposed to chemotherapy, I think it leads to potentially longer duration.  

And my hope would be that we never need to give CAR-T cells to anybody, I mean in terms of that because if we could get them into remission with other approaches.  But, unfortunately, right now it seems like patients still become resistant of the cells and get (inaudible?) to the cells, become resistant to ibrutinib and then they become resistant to venetoclax, and when that kind of happens you should be thinking about your other options, and CAR-T cells are a good one at that point.  

The one exception is in patients who have a type of CLL where the IgVH is mutated and they don't have other abnormalities, it appears that some of those patients are actually cured by that chemotherapy.  And so that's maybe the one exception.  You know, you'd say, well, gee, yeah, chemotherapy might be bad, but if there's a 60 percent chance of being cured if I'm in this sub-group and never have to go on treatment, that could still be a situation where you would want to consider chemotherapy.  

But for patients with high-risk disease or unmutated IgVH, then we're generally thinking that chemotherapy is not the mainstay any more.  All this said, you know, being on a—you can't—I've had people on ibrutinib for eight or nine years, but there are side effects with ibrutinib.  A lot of people can't stay on it.  They have, there's problems with nausea.  Sometimes problems with bleeding.  There's cardiac arrhythmias, and so—and there are, there can be some fatalities from even being on ibrutinib.  And so it's not a completely no-risk drug, and ideally we would give a short course of therapy, limited to a year or two, and then be able to stop it and have people be in remission.  

Now we're really—the treatment paradigm is evolving because in the old days we didn't even know what a complete remission was.  We would say complete remission was less than 30 percent CLL in the bone marrow.  Well, nobody believes that anymore.  Now we're talking about minimal residual disease, one in a million cells by deep sequencing or at least one in 10,000 by flow cytometry, and that's really—that's where the future is.  And so I think we're going to cure CLL, and we're going to get to the point where the only acceptable answer is no detectable CLL. And that should be the goal of therapy. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on August 21, 2019