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Treatment Options Along the CLL Journey

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Published on April 8, 2021

What Treatment Options Are Available for Individuals with CLL?

What are the available treatment options at different points in the CLL journey? What questions should patients be asking their care team to ensure the best of care? As more advanced treatments become available, will the role and duration of watch and wait change?

In this video excerpt from our "Evening with the Docs" event, host and patient advocate Michele Nadeem-Baker is joined by Dr. Faithlore Gardner, MD, Medical Oncologist/Hematologist and Dr. Maen Hussein, MD, Medical Oncologist/Hematologist at Florida Cancer Specialists to discuss treatment options along the CLL journey.

Support for this series has been provided by AbbVie, Inc. and Genentech, Inc. Patient power maintains complete editorial control and is solely responsible for program content.

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Transcript | Treatment Options Along the CLL Journey

Michele Nadeem-Baker: I'm Michele Nadeem-Baker, a CLL patient, and your host tonight from Patient Power. We have oncologist-hematologists here to discuss chronic lymphocytic leukemia, CLL, from Florida Cancer Specialists & Research Institute.​ I would love to introduce you to our doctors this evening who will be our experts and residents. I have Dr. Maen Hussein – thank you for joining us tonight – and Dr. Faith Gardner. Dr. Gardner, I would love for you to introduce yourself and give the audience a little bit of information about you​, where you are and how you’ve gotten here.

Dr. Gardner:  Hi everyone. My name is Dr. Faithlore Gardner. I'm actually practicing here in the Fort Myers Cape Coral area. I'm here in Florida with Florida Cancer Specialists, I've been here now for over six years. And essentially, here at Florida Cancer, we do see quite a variety of different malignancies, both heme and solid tumor. But I do actually have a lot of patients with CLL, some who are just being observed, and some who are on active treatment.

Michele Nadeem-Baker: Thank you. Dr. Hussein?

Dr. Hussein:  Hi. My name is Maen Hussein and I live in probably the fastest growing city in the universe, The Villages. Well, I work in The Villages. I've been in Florida since 2006, I treat many CLL patients. I'm hoping we'll have a nice informal chat to help our patients cope with this disease.

Michele Nadeem-Baker: That's great. There's so much right now regarding different kinds of treatments. Let's jump into that, the different types of treatment. We have BTK inhibitors, we have monoclonal antibodies, we have combination therapies. We have so many different kinds of treatment. We also have BTK inhibitors, they've been out awhile. And I actually was on a trial that was the old standard chemotherapy. I would love to know if either of you are still prescribing that with a BTK inhibitor, with ibrutinib (Imbruvica). And then we have the CD20 monoclonal antibodies, and we also have the Bcl-2 inhibitors. We just have so much going on out there, it's great.

There's so many choices for patients that didn't exist and now they do. And there's so much more into research. We know when it's time for treatment. That seems to be patient by patient. But how do you know, when it's time, which treatment's the best treatment, Dr. Gardner? How do you choose with this? Now there's this plethora of choices, chemo, or no chemo. I'm just curious if you still prescribe chemo, and if so, when, and how do you know if it's time for a BTK inhibitor or if it's something else?

What Are the Available Treatment Options at Different Points in the CLL Journey?

Dr. Gardner:  So I will be honest, I would say for the majority of my CLL patients, chemo is not really an upfront treatment that we're doing right this minute. I think we can do a lot with targeted therapy and immunotherapy, as you mentioned. A lot of the treatment backbones now are going to be combination therapy, whether it's with the BTK and a monoclonal antibody, the anti-CD20, as you mentioned, or the Bcl-2 inhibitor and also the monoclonal antibody. And I think the big questions, the discussion I have with my patients, is really whether or not they want the duration of treatment. A lot of the BTK treatments require – that's the Bruton's tyrosine kinase inhibitors – they require that you be on treatment indefinitely. So, it's continuous treatment. So once you start on that medication, you stay on that medication unless your disease progresses, or you have some significant adverse effect that requires that you come off the medication. Versus the combination of the Bcl-2 inhibitor, venetoclax (Venclexta), with an anti-CD20 is really a fixed duration of therapy, which is about a year or at best two years.

And so, for patients that have this conversation, pros and cons of both, and then a lot of my patients end up, as you said, to have involvement and they guide me in terms of what they would prefer. There are some people who like the idea of just staying on this pill and their disease is under some fairly good control. I think right now with ibrutinib, we have going up on seven years now, data of patients doing very well with that medication. And then some patients are wanting to basically be able to have treatment for a finite period and then be off treatment. So, that helps in that discussion.

And then one of the things that we talk about in the beginning is their prognostic factors, their mutations. One of the most significant mutations that we see in CLL is the TP53 mutation. That also helps guide us to what treatment they get. We know that patients with CLL that have a TP53 mutation or deletion 17p, that they don't do well with chemotherapy. So, they definitely are someone you'd want to think about doing more targeted therapy or the immunotherapy as opposed to chemotherapy. And I'll give Maen a time to talk.

Dr. Hussein:  I just say ditto. Exactly what you said. I think and I agree with... I don't think I started chemotherapy on CLL in the last five, six years, maybe. I really don't remember the last time I gave FCR or chemotherapy to a CLL patient. I think the main two options we have is a BTK inhibitor, with or without the CD20, or the Bcl-2 inhibitor with an anti-CD20 monoclonal antibody. And the difference is the BTK is just like they said. We don't know... As far as we're concerned, you have to stay on it indefinitely, although there's some research now about trying to look at MRD and if it's undetectable, then maybe you can stop it. Some people are looking into a finite duration while the Bcl-2 is one to two years.

My problem with the Bcl-2 inhibitor is just, the bone marrow tanks. The blood count goes down and a lot of patients, they become so neutropenic or thrombocytopenic that we have to stop it or adjust the dose. But it works and it's weird because even when they’re neutropenic, they’re not as sick as when we see neutropenia with chemotherapy, for instance. Those are the two main options. Of course, there are some patients who may still benefit from chemotherapy, like maybe the younger patients. Maybe they have a big burden of disease, you try to do that. But just like they said, if they have a chromosome 17p deletion those patients are not going to respond to chemotherapy. So, I would not even recommend chemotherapy. I try to find clinical trials and we do have, actually, clinical trials for first-line and second-line. So, I did enroll patients in clinical trials, and most of those trials are new BTK inhibitors or combination of BTK and Bcl-2 inhibitors.

Michele Nadeem-Baker:  One of our audience members has asked if it's time to rethink the active surveillance period, and they're asking, with the new novel agents, would that mean that that could be a shorter duration and go into treatment more quickly? I know we spoke about it when it's time for treatment, but why can't patients be treated instantly, and then could they be treated more quickly with the new novel agents?

Will the Role of Watch and Wait Change as More Advanced Treatments Emerge?

Dr. Gardner:  That's a very good question, and I think that's what a lot of patients get frustrated about because they have this cancer diagnosis and, “Why don't you just treat me right away?”. And the answer to that is really because even with these new combinations and novel treatments, it's not necessarily a cure. As Maen mentioned, we can get patients that we get into deep remission, this MRD, which is minimal residual disease. So, you barely see any evidence of the CLL, but it's still not yet a cure. And so, when you're in a situation where you're not curing the disease, you really have to weigh the benefits of the treatment against the adverse effects of the treatment.

As it was mentioned before, one of the significant adverse effects with that combination of the Bcl-2 and the obinutuzumab (Gazyva), the counts are getting very, very low. Someone's very neutropenic. They can end up in the hospital with neutropenic fever or sepsis. Thankfully that has not happened, but that's a risk that they could get very ill, very sick. Some may even pass away from that. With the Bruton's tyrosine kinase inhibitors, you have risk of atrial fibrillation, bruising, dizziness. I've had people who've had reflux, joint aches, pain.

Dr. Hussein:  I think the first rule of medicine is do no harm. So, if there is no harm there, why add these... Just like Faith said, these are good drugs, but they're not 100% safe drugs, and they do... People can die from complications. Like atrial fibrillation, people can die from that if you don't catch it on time. Bleeding, people can have like intercranial hemorrhage, bleeding in the brain or they can bleed in their bowel where we don't see it, and people can die from that.

So, they're very good drugs. They have some safety profile that can be concerning. And they're very expensive. And we have to be conscious about that, the economy. We don't have the luxury of giving all these expensive drugs for patients who... We have to weigh the benefits and risk of even the cost factor. And is it worth it, especially if it's not going to improve the survival to those patients who are not symptomatic. We don't have data to show that survival, they're going to live longer if they get those drugs at the earlier stage of their disease, when they're not symptomatic.

Michele Nadeem-Baker: Thank you both. Thank you for all that you've both shared with us. ​I'm Michele Nadeem-Baker for Patient Power. Thank you so much for joining us.


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