Cleveland Clinic Cancer Center's CHIP Clinic

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology.Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shephard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today I'm happy to be joined by Dr. Bhumika Patel. Bhumika oversees the development of a CHIP Clinic here at Cleveland Clinic. She's talking to me today about CHIP and our efforts here at Cleveland Clinic. Welcome, Dr. Patel.

Bhumika Patel, MD: Thank you for having me.

Dale Shepard, MD, PhD: We're going to talk in a little more detail about the CHIP Clinic, but maybe you can start off telling us a little bit more about what you do here.

Bhumika Patel, MD: So, I've been at the Cleveland Clinic, I've done two fellowships, one in Translational Hematology Research and my Hematology Oncology training. And I'm in my second year as staff, a part of the Leukemia Group at the Cleveland Clinic.

One thing that's been exciting for me since I've started as an associate staff is being able to develop this CHIP Clinic and being able to be a part of it at every aspect of it, and seeing the growth of it over the last year and a half. So I'm really excited to tell you guys about it and tell you all the headways we have made and what we're planning on doing, and what the future looks like for this clinic. So I'm really excited to share that with you guys today.

Dale Shepard, MD, PhD: All right, well, let's dive in. I'm going to start really, really basic. So for everyone listening out there, what is CHIP?

Bhumika Patel, MD: So a lot of times these acronyms get a little tricky and fuzzy for patients, but I think the main thing to know about CHIP is, it's Clonal Hematopoiesis of Indeterminate Significance. So when we take this acronym, the biggest thing to know is that it's detection of a somatic mutation, which is a mutation that is a change in your DNA, acquired. It could be acquired, or it could be inherited.

But most of the CHIP mutations that we're going to be talking about, somatic mutations that can be detected in a healthy individual, which we commonly find in patients with aging. But we can find it in 10 to 20% of the population of greater than 70 years of age and less than 1% in less than 40 years of age.

Detection of CHIP is usually found in the settings where we're actually screening, when patients are actually undergoing workup for their solid tumor malignancies, hematological malignancies in our setting, survivorship, or in patients that are undergoing bone marrow transplant and donors that are donating.

Dale Shepard, MD, PhD: Excellent. Now your interest in this CHIP clinic, is this an extension of the work you did through your fellowships, or how did you get involved in this?

Bhumika Patel, MD: So a lot of my work since I started seven years ago at the clinic, it's been in genomics research. So I've been studying bone marrow failure conditions, which involves aplastic anemia, T-LGL, PNH, MDS, and AML. And CHIP is a precursor condition to these other conditions that can occur.

So where my interests came is what are the implications of these CHIP mutations? Large population studies have been done where we've detected CHIP in healthy individuals without a history of cancer and which we've noted with aging. And we've noted CHIP mutation in patients at high-risk cardiovascular disease patients also.

So I think that's where my interests continue to go because I was an Internal Medicine doctor before coming here to do my Hematology Oncology training. But the conglomerate of what we can do better for preventative care for patients who are in survivorship for their primary malignancy, and that's been treated or cured. And also how are survivors, they're already taking a part and making sure they're following through with all their physician appointments. Well, what can we do to improve their lifestyle and doing preventative care that actually improves their quality of life and longevity of life?

Dale Shepard, MD, PhD: We know what CHIP is now. Tell me a little about the clinic. What does the clinic look like? Somebody comes to the CHIP clinic, what exactly is it?

Bhumika Patel, MD: So, in the CHIP clinic, so right now, just to give you guys a little background. When we implemented our research protocol in identifying patients with CHIP, we've started our CHIP clinic in first, screening patients in our breast and head and neck survivorship patients that have been enrolled in the survivorship, that have been cured from their malignancy and with no evidence of reoccurrence or any evidence of metastatic disease within the last year.

These patients, we present them our protocol and they agree to be a part of this study. And then when they undergo next generation sequencing, which is genomic sequencing of their blood, peripheral blood testing, if they have a detection of a mutation what happens is those patients, I review results of their testing. And if they are tested positive, I discuss the results and bring them into my clinic, see what we can do to risk modify risk factors for patients with CHIP. Because we know CHIP mutations increase the risk for cardiovascular disease and for hematological malignancy.

So our goal is to modify the risk factors we can and understand what monitoring these patients need. And also making sure we are at the forefront of helping to develop guidelines of what we should be doing with patients with CHIP. Because CHIP, along with the spectrum of other conditions called clonal cytopenia of undetermined significance, where you have actually abnormal blood counts in a mutation, these are all precursor lesions to myelodysplastic syndrome in AML. So we want to make sure we are at the forefront of guidelines and how we should be managing these patients, and also taking care of them and doing preventative care for them.

Dale Shepard, MD, PhD: So you mentioned this being part of a research protocol. Is the clinic really part of a bigger research effort, and if so, how many patients do you anticipate enrolling?

Bhumika Patel, MD: So as of now, with the COVID-19 pandemic, our protocol opened up right at the start of the pandemic. So even with the pandemic and how things have slowed down in enrolling patients into our protocol, but with the last two months we've enrolled up to 41 patients total, which I think is really a lot, especially with the ongoing pandemic that we're in. But I do expect that our enrollments are going to continue to increase in this realm, especially in the head and neck and breast cancer group.

But I do think once we lay our foundation down in survivorship, I do think we're going to be able to screen patients in the upfront of newly diagnosed patients with solid tumor malignancies where we can CHIP. I hope we are able to look at other survivorship groups within our cancer center where we can expand screening patients for CHIP. And closely work with our HBI, where we may consider also screening high-risk cardiovascular disease patients for CHIP mutations. Because we know patients with high-risk cardiovascular disease are also at high risk for having CHIP mutations.

Dale Shepard, MD, PhD: So it certainly makes sense that you've reached out to head and neck and breast because of the survivorship link. Are those or other tumors more likely to have patients with CHIP mutations? So give us an idea of the incidence, how often do we see it? I mean, 41 patients over a couple of months, that sounds pretty good. What kind of numbers are we talking? What's the impact here?

Bhumika Patel, MD: So just to give you our insights, so right now out of 41 patients I've had one patient positive. So it tells you the incidence of CHIP is very low. In a healthy average population the incidence with age of less than 40, 1% of patients will have a CHIP mutation. But as age increases greater than 70, 10 to 20% of those individuals will have a CHIP mutation.

In the setting of solid tumor malignancy, we've seen it up to anywhere with 5%. You can talk about breast, lung cancer, and GI malignancies, up to 5% or less we've seen a detection of gene mutation. But there's more studies coming out, prospect of studies showing that incidence may be higher. I think these are all retrospective studies where we have detected where there's tumors sequence in conjunction with peripheral blood, where we've been able to look at the incidence of these rates.

So it's not as common as identification of a primary malignancy, but this is in conjunction that it could be detected when you're evaluating patients. So for example, a patient with newly diagnosed lung cancer that is undergoing FoundationOne testing or any genetic testing for their workup, they may be found to have their lung cancer associated mutation. But at the same time that panel may include mutations that are found commonly in hematological malignancies. When I say that it's any type of MDS or a lymphoid malignancy.

But that's important to keep in mind because that shows us that there is, depending on the variant allele frequency, which is the mutant burden in the peripheral blood, you may want to assess is there associated abnormalities with the blood or is there not? Or is this just a passenger mutation that we may need to keep a track of as we're treating the patient for their primary tumor?

Dale Shepard, MD, PhD: And has the data suggested that, you mentioned age before and about incidence, and so certainly it seems like as people get older, you mentioned that there's more likely just to have CHIP mutations. Do you think it parallels maybe age more than tumor type? I guess when we think about expansion is that maybe geared more toward older patients or more toward tumor types, or how does that look?

Bhumika Patel, MD: So I think I would look at it in parallel. So I think age is one. I think with aging in general, because there's senescence of our bone marrow, and with aging in general, the risk of cancer incidence increasing. I think that's one lane we're in. I do think patients that we're treating upfront with solid tumor malignancies and hematological malignancies, I do think there is a concern that patients may already have a pre-existing mutation. Whether it's a somatic, which is an acquired mutation or a predisposition, like a germline mutation, which may increase their predisposition to having a malignancy.

But I do think there may be overlap between clonal hematopoiesis and a primary malignancy. I think there may be overlap between those two conditions. But I do think this all merges with aging. Also, I think the incidence of the primary malignancy and everything merges together, where we have to look at the coexisting comorbidities, their primary tumor, and their age. All of that together, what are we doing to assess the impact of CHIP? What is the role of CHIP in these patients? And I think that understanding that and the interdisciplinary interactions which in all these multifactorial factors is going to be very crucial.

And especially with the chemotherapy and radiation therapies and the new advents of therapy, I think therapy is going to play a big role. Because if there's a patient with a pre-existing CHIP mutation prior to even starting any type of therapy, we may want to assess, does radiation or chemotherapy expand the CHIP mutation, does it eliminate that, or does it actually accelerate that mutation? Does it cause it to acquire more mutations or does it make the risk of developing a cancer more fastened at point A to point B?

Dale Shepard, MD, PhD: I guess I would, as I take a look at this, I would say kudos to you because this seems really hard to study. And when I think about, you're by nature, looking at something we don't know how important it is because there's not necessarily a direct causal link. And that's what you're trying to study. And so what's the timeframe we're looking at? So, you saw 41 patients in a survivorship clinic. One had a CHIP mutation. When do you think that might express itself clinically into something we can make those correlations? How do you think through how you make those connections?

Bhumika Patel, MD: So I think all these associations have been made. I think a lot of associations need to be better understood at a basic science level and at a clinical level. So we know the risk of CHIP going to cardiovascular disease, strokes, thromboembolic events has been well study and hematological malignancies. It's constantly evolving and we're understanding more, especially about the inflammation pathway also.

So I think the big thing that I see is that I think this is going to be a long-term study. I think it's going to be over 10 years, to be honest with you. Because the incidence of CHIP causing a hematological complication is 0.5 to 1% per year, if you have a CHIP mutation. So the risk is very low. And I think the complications with cardiovascular risk factors is going to be well understood. Because as we're seeing the risk of obesity, cardiovascular disease increases with age, and we're seeing that more and more just in the general population. I think these are going to be all interlinked of understanding environmental factors that may be contributing to clonal hematopoiesis. And in the setting of malignancy, any type of cancer, we're going to be understanding all the factors that are playing a role.

So I think this is going to be a long-term study. I don't think we're going to have short-term data. I think we're going to have large prospective studies, and I think it's going to have to be multi institutional to study it. Because if you look at all the data studies that have been published to date, all large cohort studies of 10,000 patients that have been evaluated for CHIP.

And now prospective studies are being done by Memorial Sloan Kettering, MGH. Everybody's developing these CHIP clinics, so we better understood what is the implication of this precursor lesion of CHIP? What is its implications? How does it play a role in the cardiovascular disease realm and the hematological malignancy realm, and in the setting of solid tumor malignancy?

If someone is cured from their solid tumor malignancy, what is their risk? What is this mutation going to do exactly? When is it going to evolve? How should we monitor these patients and how do we eliminate... It is going to be stressful, right? The more genetic information we come out with is going to be stressful for physicians and patients. How do you deal with the psychological impact of this?

And how we manage that is going to be crucial, and I think one thing we're really lucky to have here at the clinic is, I think, the multidisciplinary approach to our clinic is going to be our strength. Because we have the CHIP clinic, we have the Heart and Vascular Institute, Preventative Cardiology group, we have great input from genetic counseling. That's going to help.

And just to give you an example. Recently, we had a normal donor who was trying to be a donor for their sibling, and they were found to have a genetic lesion that could be potentially germline. And we were able to talk the patient through this and make sure we were able to help them assess. Because if they're living a healthy lifestyle and they're doing everything, like no medications, nothing. They were just trying to be a donor for their loved one. And in that setting we were able to help the patient with genetic counseling, talking them about their implications of these mutations, what type of monitoring we would consider and talk about that.

I think these are going to be important cases that we will be managing. But I think this is going to help create bigger guidelines for a national forefront with other institutions as we work together in helping, managing these patients with clonal hematopoiesis of indeterminate significance and clonal cytopenias of undetermined significance. Also, I think there's going to be a continuum of diseases that we are going to be better understood in helping managing these patients.

Dale Shepard, MD, PhD: So this is an important but small field at this point. So have there been good opportunities to collaborate with these other institutions?

Bhumika Patel, MD: So, since I've started, in the last year and a half the biggest collaboration we have been able to do is within our internal Heart and Vascular Institute. Just since February, we've been able to get all this launched. But I do look forward to... Recently I was part of a meeting where every expert of clonal hematopoiesis was on there from the early studies.

And I do think there's going to be a room where the more data we collect, we're going to be able to collaborate with other CHIP clinics across the nation, such as Mass General and other institutions that are building their clinics. I think there's going to be definitely opportunities for us to collaborate, put this data together in different aspects. And I think there's more to come for this.

And I do think that it's just going to take time and it's going to take funding for us to continue expanding our efforts in better understanding CHIP, its implications and outcomes in the long run. I don't think this is going to be a one or two year study. I think this is going to be a long-term study. And I think it's going to have implications, not only for healthy individuals, but for all of our cancer survivors and implications for how we treat patients moving forward.

Dale Shepard, MD, PhD: You mentioned a very important part and that's funding. This is something that's being done in a research setting. Is there any thought that this might be covered at some point, or is that going to represent a barrier as we move forward?

Bhumika Patel, MD: I do think right now with sequencing, we do have insurance barriers. So there's an economic cost. So right now with the current funding we have we're able to do the next-generation sequencing with the current funding. But I do think in the future for this to become a standard of care, I think there will have to be more data for insurance companies to cover this as a type of routine workup for patients. Because these panels cost several hundred to a thousand dollars, depending on which company you're using.

But I think it's definitely going to be an obstacle in the future, but I think research is where it's going to have to start. Because I think this is going to be a place where we can actually identify the implications of it first and what are the outcomes, what we are able to change, and what we are able to do to better serve our patients, because that's going to be the pivotal point for us moving forward.

Dale Shepard, MD, PhD: You mentioned the important part about stress earlier. So have you noticed any issues with patients and their acceptance to get genomic testing and that fear of the unknown and what you might find? Has there been pushback by patients to have this testing, or they all seem to be pretty eager to join in and learn something?

Bhumika Patel, MD: So I can say there's two experiences I've had with genetic sequencing. So in the setting of already known type of blood cancers, patients are eager. They want to know if they have a targeted lesion where they can get a pill for. So most patients, I have not had an issue in the heme malignancy. And even in the survivorship group, patients are eager to improve their care.

But I think a big thing comes in communication with your patients and explaining to them what we can find and what would the implications be for them, and painting a realistic perspective. Most of the time these panels are so vast and we don't have targeted drugs for all of these panels for all the genetic lesions. But I think explaining it to them, they're more eager to want to know than you would suspect. And I think explaining it to them is very crucial.

And I think that's a position you have to make sure that we explain the implications. So that if we do find something on these next-generation sequencing panels that could have germline implications, meaning something that could be inherited, I do think that we, as physicians, should make sure we convey that to the patients. And make sure they understand why we are recommending they see a genetic counselor. So that way, they can get the proper workup with their loved ones if indicated clinically. I think that's where having the genetic counselors in your clinics are very important in making sure you're making them involved in the care of these patients.

Dale Shepard, MD, PhD: So I guess a final question, if this turns out it works, you find targets, what do you think is the ultimate goal? Do you think it's going to be more prevention or early detection of a problem that could maybe be treated, or maybe both? How do you think this is going to pan out in terms of success?

Bhumika Patel, MD: So, definitely from the standpoint of success, I think this is going to be a long-term success. That's one thing to say, because I think we're going to need long-term data. But I do think early detection is going to be a key. Post-monitoring is going to be the next, active surveillance. But the third thing is this is going to help us develop clinical trials to see what we can do to mitigate the risk of progression potentially.

So I think the big picture for everybody globally, I would say in this area, is what can we do to prevent propagation of these clones? What can we prevent expansion of these clones? Do we do anti-inflammatory? So, if this patient has hypertension hyperlipidemia in a CHIP mutation, how do we aggressively risk modify the risk factors they have? Maybe they will have implications that they may not have clonal expansion of these mutations they have.

So I think that's a good place where we're starting right now. I think there's going to be larger realms where we're going to have guidelines to help manage these patients in a larger front. So I think we're working on prevention. I think early detection. I think active surveillance and intervention. I think these are four things are working together to help us better manage these patients.

Dale Shepard, MD, PhD: Well, you've offered us some tremendous insight today and thank you for that. And thank you for being with us.

Bhumika Patel, MD: Thank you for having me.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget you can access real-time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.