Chronic Lymphocytic Leukemia Pathways in Practice at Rocky Mountain Cancer Centers

John Burke, MD, Rocky Mountain Cancer Centers, Denver, Colorado, speaks with the Journal of Clinical Pathways about the current treatment landscape for chronic lymphocytic leukemia and how his center ensures a comprehensive approach to patient care.

Transcript: 

John Burke, MD: My name is John Burke, and I'm a hematologist and oncologist at Rocky Mountain Cancer Centers in Metro Denver, Colorado.

With the increasing focus on personalized medicine, how do you incorporate genomic and molecular information into the treatment decisions for your chronic lymphocytic leukemia patients? Are there specific biomarkers or genetic mutations that you find particularly informative in tailoring treatment plants?

Dr Burke: Yeah, thank you for the question. So in terms of what genetic mutations and biomarkers I use in my practice, I would say, there's several. First is, we do a FISH analysis on all CLL patients for mutations that are known to be common in CLL. We also check the mutational status of the immunoglobulin, a heavy chain, variable region, or so called IGVH, or sometimes referred to as LGHV, which we know to be prognostic in terms of treatment outcomes for patients. Finally, we do a next-generation sequencing panel for most of our CLL patients, where of particular interest is the results of a TP53 mutation, which has prognostic implications and may impact one’s treatment to some extent. So those are probably the key things we do and one final way of using sort of sort of molecular information is to look for so called minimal or measurable residual disease, often abbreviated MRD. And that can be done in a in a couple of ways, one of which is flow cytometry. I personally often use that next-generation sequencing panel called the clonoSEQ when I'm using a fixed duration, venetoclax-based therapy for patients to track their disease in a more detailed fashion than one can do which is conventional, you know, CBC monitoring.

So those are examples of how you know we use, or how, what, what information I would say we test for. You know exactly how to use, that is a little bit debatable. If you looked at, you know, in in the past, when chemoimmunotherapy was commonly used for CLL, I think maybe those test results had a little bit more critical significance, because chemotherapy and immunotherapy might be used for a patient without say, deletion of 17p or a TP53 mutation that would confer a higher risk, and therefore a less favorable outcome with chemoimmunotherapy.

And so, for example, one could choose chemo immunotherapy for a patient without one of those high-risk mutations, but use one of the targeted drugs for patients with the high-risk mutations. Nowadays, where we are applying the targeted drugs and the immunotherapy as opposed to chemo for the large majority of patients, if not all patients, you know, the relevance becomes perhaps a little bit less you know, and if you look at, say, NCCN guidelines nowadays, they pretty much suggest the same regimens, for whether a patient has those mutations or not. So, for example, BTK inhibitors and venetoclax and obinutuzumab as initial therapy for patients with CLL are both reasonable and recommended frontline treatments, whether a patient has a high-risk mutation or not, whether the patient has an IGHP mutation or mutational status as mutated or not mutated. So I think the distinction has been blurred a little bit. And the treatments that we typically use, particularly the frontline setting, kind of have been blurred and spread across both those with high-risk mutations and those without high-risk mutations. So it's, one could argue, it's a little bit less critical nowadays to kind of know that information than it was in the past.

There is an argument to be made to use sort of continuous BTK inhibitor therapy in those with the deletion 17p or TP53 mutation, based on what appears to be better progression-free survival in those patients with such therapy, and so many experts now will advise use of the BTK inhibitors as continuous therapy, and those with those mutations over, say, use of a venetoclax CD20 antibody combination. So that's a scenario in which one could really use high-risk mutation to pick between targeted therapies. I would still argue that, one, we don't know that there's an overall survival benefit for that strategy. And so it's still very reasonable to use venetoclax as well in such patients. But that's a scenario in which people do sometimes, you know, choose between targeted therapies based on the genetic testing results.

Given the complexity of CLL and the potential for various medical issues to arise during treatment, how do you collaborate with other health care professionals, such as hematologists, pathologists, and supportive care teams, to ensure a comprehensive and holistic approach to patient care?

Dr Burke: Yeah, great question, I think the way in which I personally collaborate with other health care professionals and I and others, is you know, probably a number of ways. I mean, I think we for one example we have within our group, we have weekly conferences where we will present and discuss cases that we find to be interesting or challenging and particularly ones where we might need some help, you know. So, for example, if I have a tough CLL patient who is refractory to a number of treatments, I'll present his case to colleagues who, unlike me, provide CAR-T cell therapy, or allogeneic stem cell transplant, which are technologies that I don't personally deliver to my patients. And so I will work with other colleagues who have expertise in those areas to discuss cases and decide on the best treatment plan for a patient with CLL.

In the pathology space we do similar things where we'll present cases where we have questions about pathology. And you know, I've lined up 4 or 5 of my own patients for next week's meeting, and 3 of them are I put on there because they have questions about pathology. And so we're gonna kind of bounce back some, bounce back and forth some questions about what does this mean, and what does that mean? And what test should I be doing here? And can I request this additional pathology analysis on something that I have interest in. So that's a way in which we work with our pathologists on a regular basis. Supportive care teams … you know, I would say, probably the majority of my CLL patients don't require, say, a palliative care consult, or things like that, or at least I, personally, for better or worse, don't involve those. But there are patients where I do. You know where somebody is having a number of symptoms and quality of life issues, or is getting toward the end of their life, and we will involve palliative care or hospice for additional management of symptoms related to their CLL. CLL's a disease that doesn't cause a ton of pain. So it might be a disease that lends itself less to sort of assistance with pain management than some other diseases in the hematology oncology field. But still, there is a role for supportive care teams to manage symptoms and other issues that patients may be having, particularly when they've got more advanced disease, that's, you know, causing them problems. So I think there are probably many other ways. Of course, with radiologists we we work with to review scans and ask questions about those. Primary care physicians we work with to help us manage other issues that we might be causing for our patients or the patients might experience. So yeah, the whole business of hematology and oncology is, you know, I don't care what disease you’re taking care of, you’re always collaborating with other health care professionals.

How do you ensure that your treatment plans are aligned with the individual needs and preferences of your CLL patients? Can you provide an example of a case where you tailored the treatment approach to accommodate a patient’s specific circumstances or preferences?

Dr Burke: Yeah, thank you. I think that's an important part of what we do every day. That is, you know, aligning our treatment recommendations with what an individual needs. It's sort of the art of medicine, really, is that, you know, practicing medicine well, doesn't mean following a cookbook. So it's you know, you gotta discuss what a patient needs. I mean, I'm just thinking, I just walked out of a room with a patient who, it's, you know, slightly different, he's got multiple myeloma, but he was asking me about this clinical trial that he's considering going on. And so why don't we go back to, you know, the first treatment that we use which worked OK? And I said we could, it'd be fine, but remember, that treatment cause you a lot of peripheral neuropathy, and you weren't too happy when you had all that peripheral neuropathy. And so he said, oh, yeah, now, I remember that. And so, yeah, so yeah, you could go with this option. It's reasonable, but it’s gonna cause you a worsening of your neuropathy, whereas plan B, you know, may not do that, or will have a lower likelihood of doing that.

And so that’s just an example of something we do every day, where, you know, you adjust for a patient. In the CLL space, it happens for every single patient who's gonna start therapy for CLL, where it's usually several fairly lengthy conversations, talking about the different options that they have, because most every patient with CLL has the option of going on a BTK inhibitor, or going on a BCL2 inhibitor and venetoclax with a CD20 antibody or going on a clinical trial, you know, and those are sort of the 3 main options I generally present to folks who are starting therapy, and some people like the idea of going on a continuous therapy because they want to keep suppressing the CLL. They like that idea, and one cannot argue with results of continuous BTK inhibition, and so some people will choose that. Others place a high value on being able to stop therapy, that is, you know, having a time limited treatment that they don't have to be on for years and years, and so those patients will accept, say, some of the downsides of venetoclax and obinutuzumab with, you know, the extra infusions and that sort of thing, and really want to go on that, and then be able be rewarded by being able to stop treatment at the end of a year. And in my hands, that's a common decision people make is that they would rather do that. Others you've talked to will value participation in a clinical trial. They want to help advance the field. They're a victim of cancer themselves, and they wanna help others who come after them, and they will. We'll volunteer for clinical trials. Other individuals will have particular health conditions that prevent them from being a great candidate for one treatment or another. I mean, the classic example in CLL is you know, cardiac issues and requirement for a blood thinner, which may increase the risk of complications if they go with a treatment like a BTK inhibitor. So if I have somebody with atrial fibrillation who's on anticoagulation, I'll probably steer them away from continuous long-term therapy with a BTK inhibitor, and either offer them a clinical trial or venetoclax-obinutuzumab combination.

So many different sort of factors go into that, and every patient is different. And it's always kind of a discussion of the risks and benefits, particularly in relation to underlying issues they have and underlying values they have, and what's important to them. And that's how you kind of arrive at a conclusion on how to treat somebody.

Living with a chronic condition like CLL can have significant psychosocial implications. How do you address the emotional and psychological aspects of care for your patients? Are there support services or interventions you commonly recommend to help patients cope with the emotional challenges associated with their diagnosis and treatment?

Dr Burke: One factor that I face in nearly every patient with CLL is fatigue. Now, maybe that's not quite answering your question, because it's not necessarily an emotional or psychological. It's more of a physical aspect, but I think it has a lot of psychological sort of impact on patients’ lives. You know. They, I would like, I can't think of anything else in CLL that impacts one's sort of mental state and enjoyment of life as much as fatigue. And it really can bring a number of patients down. And so that's often kind of a challenge in CLL, particularly in early-stage CLL, where patients feel like they really are fatigued, they really believe that their CLL is causing that fatigue. It's tough to prove whether it is or not, but you know, oftentimes one can only assume that it is, in fact, responsible for excessive fatigue that they're experiencing in their lives. And you know we're all trained not to treat CLL early, and that's something that I spend considerable amount of time talking with patients about is their level of fatigue, their desire to receive treatment or not receive treatment based on how much fatigue they're experiencing, and the potential risk that they're incurring by starting on treatment.

So that that really comes up quite a lot in in my personal practice. And it's not something that I usually get support services for, or other interventions, but it is something where sometimes we'll think about treating their CLL, even if it is early stage, if they're particularly bothered by this fatigue, and you're pretty sure that that fatigue is, in fact, due to their CLL, to the best of your ability to sort of rule out other potential causes of their fatigue. Beyond that I think, you know, other support services that I utilize regularly are social workers. We have social workers in our practice, who help patients who are dealing with emotional or psychiatric or psychological sort of challenges, whether that be anxiety or depression or, you know, social issues, housing, and other things related to that. So we use our social workers in that way to help patients. And for those who are in need of sort of more serious psychiatric care they tend to help us place those patients in proper hands to help managing that things, and other interventions we use is sometimes we'll all prescribe an antidepressant or something like that for somebody, if they're having challenges with depression, even if it's related or unrelated to their to their CLL. So those are some examples of things that we do for patients who are facing those emotional and psychological challenges.

The other thing is support groups. You know there are a number of these out there, and I will not infrequently refer my patients to groups that are, you know, really in place to help patients in the situation. So the CLL Society is one example, that Leukemia Lymphoma Society is another, Lymphoma Research Foundation for my lymphoma patients. So a number of nonprofit organizations like that have things like education programs, support groups where they get on and talk to other people with their disease, again, they'll put on, you know, educational lectures and webinars for patients. They have First Connect program where they can contact other people who've been through their treatment before and ask what their experience was, and get tips from their peers. So those are other resources that I do commonly use for my patients.