Tag Archive for: PV

Advice for Hesitant MPN Clinical Trial Participants

Advice for Hesitant MPN Clinical Trial Participants from Patient Empowerment Network on Vimeo.

What should MPN patients know about clinical trials? Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London shares information about the varying degrees of clinical trials and advice to those who are hesitant about clinical trials.

See More from Best MPN Care No Matter Where You Live

Related Resources:

New Developments in MPN Treatment Landscape

What Are the Unmet Needs in Access to MPN Care?

How Can MPN Patients Become More Proactive in Their Care?


Transcript:

Dr. Nicole Rochester: 

It’s said that clinical trials are tomorrow’s medicine today, and you’ve already kind of alluded to the importance of clinical trials as it relates to MPN. What would you say to an MPN patient who is on the fence or may be concerned or afraid of participating in a clinical trial?

Dr. Claire Harrison: 

It’s right to be cautious and, you know, careful because ultimately it’s a huge privilege as a clinician that involves patients in clinical trials that my patients trust me and trust my team to look after them with something that is experimental, but remember there are varying degrees of experimental. Most clinical trials are not first in man, you’re not a complete guinea pig, it may be a drug, for example, navitoclax is in clinical trials mainly for myelofibrosis also ET and PV but that is a drug that has been used for thousands of patients, for another indication so talk to your healthcare team, if you don’t find the answer from the primary person that you’re used to dealing with, find someone else, be linked to somebody you trust and that you have a good relationship with, take someone with you to the consultation, write down the questions I’m so sure you say this all the time, don’t you Nicole to the people that you talk to, but write down your questions, don’t be afraid to ask them again, there is no stupid question in this context, you will be given a 30-plus page booklet to read, and I lost count of the number of times, my patients go, yeah, I’ve got this, or I trust you.

Actually, you know, you need to read it…we are experimenting on you, and you need to read that and understand. And you need to understand, what happens if I go on the control arm, will I be able to cross over? How many visits will I have, will I have to pay for those visits, etcetera. It’s all really important. But ultimately the relationship with your healthcare provider is important, and using an advocate is really important too.

Dr. Nicole Rochester: 

I agree 100 percent. So important, these are things that I talk about all the time, so I really appreciate that you highlighted that, and just the importance of patients taking an active role in their medical care and also the trust that is required between the patient and their treating providers. So I really appreciate that. Do you have any examples, Dr. Harrison, in your own practice of successes with MPN patients who have participated in clinical trials? 

Dr. Claire Harrison: 

Oh yes, I think I started doing clinical trials, well golly, a long time ago. I think my first clinical trial, probably the records were written parchment to be honest, but we’ve still learned a lot from that, so that was an ET study. It was from that study we understood about the JAK2 mutation, and we understood how patients behave differently. I think probably the most gratifying thing for me was being involved in the JAK inhibitor studies in myelofibrosis and being involved in delivering ruxolitinib and Jakafi to patients and seeing the benefits for those patients. 

Big things, you know, there are patients who are alive because they took part in that trial today, I think, but there are also patients for whom small things were also really important, so as a patient, that’s important to define what is the benefit you want to get. So one of my first patients, you haven’t been able to have a bath or a shower for years, because he had terrible what we call aquagenic pruritus, itching induced by contact with water, we called him two days after he started ruxolitinib (Jakafi), and he was in tears, he could take…or you can take it out.

These things are really important. Like myself, I can imagine not being able to dig it out, I would either be very tough for another patient, it was, well, I looked really skinny because I’d lost loads of weight and I put weight on, and body image was really important as well, but then the small things like being able to be…participate more in family activities is really, really important too. 

MPN Treatment Strategies for Patients Who Have Failed Traditional Therapies

MPN Treatment Strategies for Patients Who Have Failed Traditional Therapies from Patient Empowerment Network on Vimeo.

What can be done for MPN patients who have failed on traditional therapies? MPN expert Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London explains some treatments under study as options for some patients.

See More from Best MPN Care No Matter Where You Live

Related Resources:

How Can MPN Patients Stay Up to Date With New Treatments?

What Is in the Treatment Pipeline for Patients With MPNs?

Advice for Hesitant MPN Clinical Trial Participants


Transcript:

Dr. Nicole Rochester: 

What about for patients who have failed therapies, are there any treatment strategies for MPN patients who have failed traditional therapies?

Dr. Claire Harrison: 

Yes, in fact, actually, that’s where we’re evaluating new therapies across all of these entities, so if you’re a PV or an ET patient and you failed a therapy, then this is where, for example, in ET, we would be looking at bomedemstat or we’re looking at the bromodomain inhibitor pelabresib, and there’ll be other agents that we’ll be looking at, or we might be looking at vaccination. And for MF patients that while there are a bunch of different therapies for patients who you have not tolerated or progressed through standard therapy. So actually, there are a lot of options, some of them are already approved, and some of them are in clinical trials. 

What Is in the Treatment Pipeline for Patients With MPNs?

What Is in the Treatment Pipeline for Patients With MPNs? from Patient Empowerment Network on Vimeo.

What does the MPN treatment pipeline hold for patients? MPN expert Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London shares insight about future treatments and the outlook for care.

See More from Best MPN Care No Matter Where You Live

Related Resources:

New Developments in MPN Treatment Landscape

MPN Treatment Strategies for Patients Who Have Failed Traditional Therapies

How Are MPN Treatments Changing for Low-Risk vs High-Risk Patients?


Transcript:

Dr. Nicole Rochester: 

Can you share a little about what’s in the robust pipeline of potential therapies for patients with MPN, what is it that you’re excited about? And is the future bright in this area?

Dr. Claire Harrison: 

I think the future is really bright from the point of view of de-escalating treatment as well as newer treatment, so I think it’s important to point that because all treatments have potential complications inside of it, so as we understand that some of these conditions may have very low risk for patients, it’s important to understand that, and de-intensify, I call that calreticulin (post ET?), I would also call out ET, essential thrombocythemia, which lacks a known driver mutation, so-called triple-negative ET, emerging data suggests that may have very low risk for patients, but what you all want to hear about, of course, is what’s new treatment-wise. 

So I think just to call out, I’m really excited that there will be a new trial this year for ET patients with Bomedemstat, which is an LSD-1 inhibitor, new target, new molecule. We’ve been testing it in myelofibrosis and we’ve tested it now in a bunch of patients with ET, and it seems to be very efficiently reducing the platelet count not affecting hemoglobin and patients appear to get a good benefit with regard to fatigue, which we know is the number one symptom for patients with MPN, so I’m excited about that because it’s been a long time since we’ve had a new treatment for patients with ET. And then for patients with PV, increasingly across the globe, the availability of this newer formulation of interferon, Besremi is becoming more available and the latest data with that agent suggests that it may be superior to standard therapy such as hydroxyurea, hydroxycarbamide in terms of clotting, et cetera, is really important.

Interestingly, and we may both have to think back to our med school days on this, we’ve been targeting the iron pathway for patients with PV. So I always tell my patients with PV, do not let anyone give you iron tablets without speaking to one of our team because that’s like putting oxygen on the fire, it’s like feeding the red cell production. So there is a new agent called Rusfertide PTG-300, which targets the iron pathway and allows iron to build up in the body, but it doesn’t allow it to get to the bone marrow and so, this is a new treatment for PV patients, which might reduce the need for iron removal by phlebotomy or venesection, and has been also shown to give symptomatic benefit, and then of course, there’s a bunch of new treatments for patients with myelofibrosis, that’s probably the busiest part of the portfolio at the moment. 

We’ve just seen positive data with me momelotinib, which is one of the fourth JAK inhibitors, very strong data from the MOMENTUM  study, good results in patients even with low platelet counts down to 25, and then I’m really excited to see strong data coming with navitoclax and pelabresib, which are other agents targeted at are the pathways in myelofibrosis. And then finally, in Denmark, they’ve been looking at vaccination strategies, and I know my patients are really interested in vaccination and gene editing. I don’t have anything new to say on gene editing), but I do have something new to say on vaccination.

So in Denmark, they’ve been looking at producing a vaccination against the calreticulin mutation, Nicole, because it’s expressed on the surface of the blood cells, so antibodies can find it. So this is ongoing, no positive result as yet, but it’s still ongoing and there are newer taking off with regards to vaccination structures, and I think that’s really exciting.  

How Can I Get the Best Myeloproliferative Neoplasm (MPN) Care?

How Can I Get the Best Myeloproliferative Neoplasm (MPN) Care? from Patient Empowerment Network on Vimeo.

 There are many exciting developments in the myeloproliferative neoplasms (MPNs) research pipeline, but how can patients get the best possible MPN care? Internationally respected MPN expert Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London shares information about research updates, treatment strategies, clinical trials, and how to achieve patient-centered care for you or your loved one.

See More from Best MPN Care No Matter Where You Live

Related Resources:

How Do I Best Communicate My Concerns Without Feeling Dismissed


Transcript:

Dr. Nicole Rochester:

Hello and welcome. My name is Dr. Nicole Rochester, I’m a pediatrician and a professional health advocate, and your host for today’s Patient Empowerment Network program. We are thrilled that you have decided to tune in. With so many exciting developments in the research pipeline from myeloproliferative neoplasms or MPNs. We’re going to answer several important questions during today’s program, how can you as a patient access the best possible MPN care? Will there be alternative treatment strategies for MPN patients who have failed previous therapies? Should you consider a clinical trial as a path to enhancing your care? Whether you’re living with polycythemia vera, essential thrombocythemia or myelofibrosis, we have so much to unpack and we are joined by world-renowned and highly respected MPN expert, Dr. Claire Harrison. Thank you so much for joining us, Dr. Harrison, it’s an honor and a privilege to join with you.

Dr. Claire Harrison:

It’s a great pleasure and it’s a privilege to join you as well.

Dr. Nicole Rochester:

Following this program, you will receive a survey and we’d be delighted if you take some time to provide your feedback that helps inform future MPN programs that we produce. Please remember that this program is not a substitute for seeking medical care, so please be sure to connect with your healthcare team to determine what is best for you. Now, let’s dive right into this very important topic, how can you get the best myeloproliferative neoplasm care. 

Dr. Harrison, we know that the treatment landscape for MPN is rapidly changing and keeping up with the pace of the developments can be challenging both for healthcare professionals and certainly for patients and their families, so I was wondering if you can give us a general overview of the treatment landscape and maybe highlight anything that’s new and in development that you think would be helpful for the audience.

Dr. Claire Harrison:

Well, sure, I think this is obviously really interesting, very important. It’s a fast-moving field. And one of the first changes actually completely hot off the press is a brand new diagnostic criteria that has been produced by two separate groups that are shortly about to be published, kind of just seeing pre-published and those of us that have been privileged to be involved, have seen them. So that’s gonna really focus the mind of clinicians on how do we achieve the diagnosis, and that’s the first thing that’s really important, get an accurate diagnosis, don’t just accept well, you’ve got an MPN, actually, it’s really important to know what type you’ve got. 

Maybe as much do you tell as possible in terms of the genetic mutation or change that underlies the disease, because that is increasingly important in what we call prognostication, understanding what the risk of events happening due to the disease actually is. When we make a diagnosis, we sometimes can’t be accurate and we might have to go back and revisit them, so some patients don’t get a PV, ET or MF diagnosis, they might get an MPN unclassified. That’s okay, but it’s important to keep revisiting that.

Once we’ve made a diagnosis, then it’s really important to think about what the risk is to the patient, and we’ve had some changes to our risk classifications recently, right from the ET end of the spectrum where we’re thinking more and more actually, those patients who are under the age of 60 with a lower count and the CALR mutation, do we even need to give you aspirin because we might be increasing the risk of bleeding. 

To the other end of the spectrum for patients with myelofibrosis, a more aggressive disease, we want to know more about your mutational profile, so we’re doing more powerful genomic tests and assessing them, your prognosis, and then what the features of your disease are that need treatment. And there are lots of changes, which I think we’ll get into later in our conversation here and lots of new options, which are really important, I just also don’t to leave this segment without saying to all of you who are listening, it’s important that you understand your disease, it’s important that you understand the diagnosis, prognosis, etcetera, and you get the best care.

But that’s maybe not enough, you need to know that you’re taking good care of you, and that’s something that’s really important to all of us, so you need to know that you’re managing your vascular risk don’t just think about your blood. Think about the fact that you know if you’re smoking, quit smoking, if you’re drinking too much, cut it down, if you’re not walking enough,  walk more, lose weight. The majority of patients with MPN actually have a problem with a blood clot, not a further complication of their disease, so maybe we’ll stop there and then we can dive in a bit more deeply

Dr. Nicole Rochester:

Thank you, I appreciate you pointing out the changes with the diagnosis. I’m really excited to learn more about that, and also pointing out the importance of self-care and some of the other risk factors that individuals with MPN can mitigate. So I think that’s extremely important. Can you share a little about what’s in the robust pipeline of potential therapies for patients with MPN, what is it that you’re excited about? And is the future bright in this area?

Dr. Claire Harrison:

I think the future is really bright from the point of view of de-escalating treatment as well as newer treatment, so I think it’s important to point that because all treatments have potential complications inside of it, so as we understand that some of these conditions may have very low risk for patients, it’s important to understand that, and de-intensify, I call that calreticulin (post ET?), I would also call out ET, essential thrombocythemia, which lacks a known driver mutation, so-called triple-negative ET, emerging data suggests that may have very low risk for patients, but what you all want to hear about, of course, is what’s new treatment-wise. So I think just to call out, I’m really excited that there will be a new trial this year for ET patients with Bomedemstat, which is an LSD-1 inhibitor, new target, new molecule. We’ve been testing it in myelofibrosis and we’ve tested it now in a bunch of patients with ET, and it seems to be very efficiently reducing the platelet count not affecting hemoglobin and patients appear to get a good benefit with regard to fatigue, which we know is the number one symptom for patients with MPN, so I’m excited about that because it’s been a long time since we’ve had a new treatment for patients with ET. And then for patients with PV, increasingly across the globe, the availability of this newer formulation of interferon, Besremi is becoming more available and the latest data with that agent suggests that it may be superior to standard therapy such as hydroxyurea, hydroxycarbamide in terms of clotting, et cetera, is really important.

Interestingly, and we may both have to think back to our med school days on this, we’ve been targeting the iron pathway in for patients with PV. So I always tell my patients with PV, do not let anyone give you iron tablets without speaking to one of our team because that’s like putting oxygen on the fire, it’s like feeding the red cell production. So there is a new agent called Rusfertide PTG-300, which targets the iron pathway and allows iron to build up in the body, but it doesn’t allow it to get to the bone marrow and so, this is a new treatment for PV patients, which might reduce the need for iron removal by phlebotomy or venesection, and has been also shown to give symptomatic benefit, and then of course, there’s a bunch of new treatments for patients with myelofibrosis, that’s probably the busiest part of the portfolio at the moment. 

We’ve just seen positive data with me Momelotinib, which is one of the fourth JAK inhibitors, very strong data from the momentum study, good results in patients even with low platelet counts down to 25, and then I’m really excited to see strong data coming with Navitoclax and Pelabresib, which are other agents targeted at are the pathways in myelofibrosis and then finally, in Denmark, they’ve been looking at vaccination strategies, and I know my patients are really interested in vaccination and (inaudible). I don’t have anything new to say (inaudible), but I do have something new to say on vaccination.

So in Denmark, they’ve been looking at producing a vaccination against the calreticulin mutation Nicole, because it’s expressed on the surface of the blood cells, so antibodies can find it. So this is ongoing, no positive result as yet, but it’s still ongoing and there are newer taking off with regards to vaccination structures, and I think that’s really exciting.

Dr. Nicole Rochester:

Wow, there is a lot on the horizon for MPN patients. That is extremely exciting, Dr. Harrison, how can patients best keep up with the new treatments and communicate with their doctors in a way that makes sure that they have access to these new therapies?

Dr. Claire Harrison:

Well, I think patient advocacy groups are really important here, and use of social media and the internet, you’re only a few clicks away from updated data, programs like these, but you also have to trust your team and trust your doctor. We all have to keep up to date. That is a professional requirement, and we also are all networked, so I’d probably get 10-15 emails a day from colleagues saying, Hi Claire, can I talk to you about this? There was an email just the other day about a patient in Washington, actually a very young child, we are all connected. 

We all want the best for our patients. But do you remember that you can contribute as a patient to advance this in your field, and I know many patients are really interested in this, if you are asked to submitting a blood sample, giving permission for us to use your data. So if we can touch maybe on the field of real world data and real-world data collection here would be good, so what about the real world data? What does that mean? And so this is becoming a really important way that’s recognized by the FDA and other approval agencies in the world, so in Europe, we have EMEA for example, and in the UK, we have NHRA as a way of collecting data on agents, so once they are approved, we collect data with regard to how the patients do. 

We’ve traditionally done this, but increasingly, as we use electronic data for our patients, we’re more able to collect real-world data, how does my patient who is with myelofibrosis on Ruxolitinib in my clinic inside East London do. So if we can pull that data, we learn a lot more about how these agents are working in patients outside of clinical trial, so you will be contributing if you allow us to collect that kind of data, we discovered JAK2 mutations, CALR mutations, etcetera from samples collected from patients and data. If you want to be part of a clinical trial, then by all means, ask your healthcare team, many MPN centers have lists of trials, and you can always look at clinicaltrials.gov, but boy you throw up a lot of different options when you search in that… On that website.

Dr. Nicole Rochester:

Thank you. I think it’s important to talk about real-world data because in this day and age, many of us are very protective about our personal health information and we should be, but as you stated, having access to that data is really a key way to advance the science and technology in the treatment of some of these conditions, so I really appreciate you sharing that.

Dr. Claire Harrison:

I think just to point out, and I’m sure the audience is acutely aware of what we learn about COVID? We learned an awful lot about COVID from real-world data from all you MPN patients who gave samples, who told us about how you did with COVID, that’s how we learned about what happened to patients during covid with MPN, how they responded to vaccination, etcetera. It’s really powerful. And your data will be anonymized, it won’t be linked back to you, Nicole Rochester, or me, Claire Harrison it will be completely anonymous.

Dr. Nicole Rochester:

Absolutely, thanks for clarifying that. I want to go back to treatment strategies, you’ve mentioned earlier about low-risk versus high-risk patients, and that some of those criteria are changing. How are treatment strategies changing for low-risk and high-risk patients with MPN?

Dr. Claire Harrison:

It’s complicated because we need to think across the entities, and we don’t have an answer to that for patients with MPN unclassified and we don’t actually have a good answer to that for this entity called pre-fibrotic myelofibrosis which does appear and is strongly recognized in the new diagnostic criteria, but for ET, for example, low-risk patients I mentioned triple negative, calreticulin, m-positive, young patients, platelets less than 1500, not too much changing their queries about aspirin or not, and then for PV patients, we haven’t really changed all kind of high-risk criteria and for both ET and PV, the questionnaire is, should we use the treatment above aspirin or above aspirin (inaudible). And for the most part, that would be hydroxycarbamide, hydroxyurea, which is the commonest treatment used worldwide or Interferon, and these are the right treatment for some patients and not the right treatment for other patients, so some patients can be very fixated on interferon is the absolute best, but there is no clear evidence of that, and there are some patients who interferon is not the right treatment, but low versus high risk becomes even more important for myelofibrosis patients.

And here, we’re thinking about using a risky strategy like transplantation for those patients who have higher risk disease, and we’re using, as I mentioned to you, these molecular markers and newer prognostic tools to stratify patients, and it is important to remember is a patient leave if someone puts your data into a prognostic tool and that comes up with five years, but it doesn’t mean to say five years on the dot your times up, that’s an average. 

And if we put your data into a slightly different tool, we might get something else. So for the most part, we make decisions like transplants,  we are learning more about transplantation and outcomes from that, and then in some countries, some treatments are used for patients who fall into intermediate or high-risk categories, and some clinical trials are based on that as well. I would want to say about myelofibrosis, and something I think I would really like to see changed, not changing yet, but changed, is that we should be able to intervene for patients with a low-risk disease. If my myelofibrosis patients have breast cancer, we would not be going there, then you’ve got low-risk disease we’ll put you on watch and wait, watch and wait is really hard for our patients, we know that I can see you nodding.

Dr. Claire Harrison:

You know that too, right? So if these were patients with breast cancer we would not say, We’ll just watch and wait. So I would really like to see in the next five to 10 years a treatment that we could use earlier in the disease course, but there is nothing at the moment, but we’re looking at that. The other thing we’re looking at, if we’ve got a minute or so is the different endpoint, so we’re trying to understand what does it mean if you’re a (?), so the amount of abnormal genes you’ve got goes down, the amount of bone marrow fibrosis you’ve got goes down. And again, this is something we’ll collect in a clinical trial, but also from real-world data.

Dr. Nicole Rochester:

Wonderful. Wow, thank you. What about for patients who have failed therapies, are there any treatment strategies for MPN patients who have failed traditional therapies?

Dr. Claire Harrison:

Yes, in fact, actually, that’s where we’re evaluating new therapies across all of these entities, so if you’re a PV or an ET patient and you failed a therapy, then this is where, for example, in ET, we would be looking at Bomedemstat or we’re looking at the bromodomain inhibitor Pelabresib, and there’ll be other agents that we’ll be looking at, or we might be looking at vaccination. And for MF patients that while there are a bunch of different therapies for patients who you have not tolerated or progressed through standard therapy. So actually, there’s a lot of options, some of them are already approved and some of them are in clinical trials.

Dr. Nicole Rochester:

And you mentioned clinical trials, and so I think this is a perfect opportunity to transition and start to talk more about clinical trials as a treatment option for NPM patients and really focusing on treatment access, what would you say are the unmet needs in access related to MPN and care, specifically as it relates to clinical trials, and what can we do to address those unmet needs?

Dr. Claire Harrison:

Well, I think there is a problem with rare diseases in terms of geographical access to trials, and we often find patients have to travel a long way. I know that’s true in North America as well as in Europe. And we’re very lucky in our geographical locations, but in some parts of the world, some companies or doing not open clinical trials, so I think there’s an access issue. I think also there is something about patients have to meet rigid entry criteria for clinical trials, and so oftentimes in myelofibrosis, for example, commonly patients who fail (?) have a lower platelet count, and that is often an exclusion criteria. Those criteria are there to try to get a uniform population of patients in a trial, but it can feel like you’re excluded as a patient, and it can feel very tough and for your health care team that we can’t include you in a clinical trial. We also have to remember that it is there for safety purposes, so if there is a lower limit for platelet count that’s often because the drug might affect platelet count. It is really important that we have a broad spectrum of trials available and that we try to increase the availability of trials for patients. 

I also want to say a word about inequality of access and thinking about accessing some different ethnicity, so often non-white and patients are under-represented in clinical trials, and I know that a focus in the UK and also in North America as well. And it is really important that patients have access to a clinical trial if they need it, and also that we understand how investigational products will work in people of different backgrounds. So for example, we know that probably Nicole, your blood count assuming it’s a healthy, normal blood count may well be different from mine for background, racial genetic differences, so drug metabolism might be different, so this is really important and we need to work hard as a community, the clinical community and the patient community to raise awareness and improve access for patients.

Dr. Nicole Rochester:

Well, as someone who does a lot of work in health equity, Dr. Harrison, I really appreciate you pointing that out. It’s certainly an issue here in the United States, as you mentioned, differential access to clinical trials, and we’ve learned that not only our patients, often not aware, but often the providers, at least here in the US, are not offering clinical trials as an option for patients from marginalized and minoritized communities. So I really appreciate you bringing that up. It’s said that clinical trials are tomorrow’s medicine today, and you’ve already kind of alluded to the importance of clinical trials as it relates to MPN. What would you say to an MPN patient who is on the fence or may be concerned or afraid of participating in a clinical trial?

Dr. Claire Harrison:

It’s right to be cautious and you know, careful because ultimately it’s a huge privilege as a clinician that involves patients in clinical trials that my patients trust me and trust my team to look after them with something that is experimental, but remember there are varying degrees of experimental most clinical trials are not first in man, you’re not a complete gene page, it may be a drug, for example, Levetoclax (?) is in clinical trials mainly for myelofibrosis also ET and PV but that is a drug that has been used for thousands of patients, for another indication so talk to your healthcare team, if you don’t find the answer from the primary person that you’re used to dealing with, find someone else, be linked to somebody you trust and that you have a good relationship with, take someone with you to the consultation, write down the questions I’m so sure you say this all the time, don’t you Nicole to the people that you talk to, but write down your questions, don’t be afraid to ask them again, there is no stupid question in this context, you will be given a 30-plus page booklet to read, and I lost count of the number of times, my patients go, yeah, I’ve got this or I trust you.

Actually, you know, you need to read it… We are experimenting on you, and you need to read that and understand. And you need to understand, what happens if I go on the control arm, will I be able to cross over? How many visits will I have, will, I have to pay for those visits, etcetera. It’s all really important, but ultimately the relationship with your healthcare provider is important and using an advocate (inaudible) is really important.

Dr. Nicole Rochester:

I agree, 100%. So important, these are things that I talk about all the time, so I really appreciate that you highlighted that, and just the importance of patients taking an active role in their medical care and also the trust that is required between the patient and their treating providers. So I really appreciate that. Do you have any examples, Dr. Harrison in your own practice of successes with MPN patients who have participated in clinical trials? 

Dr. Claire Harrison:

Oh yes, I think I started doing clinical trials, well golly a long time ago. I think my first clinical trial, we probably the records of written parchment to be honest, but we’ve still learned a lot from that, so that was an ET study. It was from that study we understood about the JAK2 mutation on and we understood how patients behave differently. I think probably the most gratifying thing for me was being involved in the JAK inhibitor studies in myelofibrosis and being involved in delivering Ruxolitinib and Jakafi to patients and seeing the benefits for those patients. 

Big things, you know, there are patients who are alive because they took part in that trial today, I think, but there are also patients for whom small things were also really important, so as a patient, that’s important to define what is the benefit you want to get. So one of my first patients, you haven’t been able to have a bath or a shower for years, because he had terrible what we call aquagenic pruritus itching induced by contact with water, we called him two days after he started Ruxolitinib and he was in tears, he could take… Or you can take it out.

These things are really important. Like myself, I can imagine not being able to dig it out, I would either be very tough for another patient, it was, Well, I looked really skinny because I’d lost loads of weight and I put weight on, and body image was really important as well, but then the small things like being able to be… participate more in family activities is really, really important too.

Dr. Nicole Rochester:

Wonderful, so what advice would you give for patients so that they can really take a proactive approach to their healthcare and feel more confident in talking about their concerns and communicating with their healthcare team, you’ve shared with us how important that is. Do you have maybe two or three specific tips or maybe questions that every MPN patient should ask their healthcare provider?

Dr. Claire Harrison:

I think the first thing to say is, in my personal view is you do not have to be under an MPN expert to get the best care. I know some people differ with regard to that, but these are chronic conditions, there are national and international guidelines, clinicians are connected. We all talk about patients over time, as we like to do that, we like to get the best for our patients, so a local center with a clinician who you trust, who you get on with… Where you can get there easily. You trust their team, you know their logistics work for you, maybe it’s a nurse who work who you get on with, well, who comes to the appointment with you, that is just as good as being under the best professor in the state, where you might not actually see them  when you turn up and go to the unit, so that’s really important, understanding your condition, and if you don’t understand being empowered to ask questions, and if you’re in a position where you can’t ask a question, something’s wrong. So don’t be afraid, take somebody with you, write it down. Sometimes it can be a mistake to do a troll on the internet, so I wouldn’t always encourage that because what’s on the internet is not always accurate, but go to a trusted website as the clinician… Where can I go to find out more information? Some patient advocacy groups run buddy systems that can also be very helpful and it can be very empowering to meet another patient with the same or similar condition, so I think those are all helpful tips from my perspective, also don’t expect to get all the answers all the time, it can be really tricky as a clinician, maybe you get a patient who comes with a big long list of questions, and say What is your top question that you really want answers to.

Dr. Nicole Rochester:

Those are awesome, awesome tips. I’m just gonna repeat a few of them, just to highlight, you mentioned prioritizing your concerns which is incredibly important, and acknowledging that the clinician doesn’t have unlimited time, and so really focusing on the things that concern you the most, you mentioned bringing a buddy to appointments, which is something I fully endorse, so that there’s someone else that’s taking notes or… It can be your eyes and ears during that appointment, things that you may have missed either because of anxiety or stress, and you mentioned writing things down, taking notes, even as the patient asking questions, which is so incredibly important, and really the way that I feel patients demonstrate their involvement in their disease and being an active member of the team, so I really, really appreciate those tips, Dr. Harrison, I think that you have given us so information, so much information about how to empower MPN patients and their families so that they can really get the best care at the outset. So it’s time to wrap things up, Dr. Harrison, I’d love to close with any closing thoughts that you have, any takeaway messages you’ve given us so many already, but if there’s anything else that you have not had the opportunity to share with the audience, I love for you to go ahead and do that now.

Specifically anything related to how they can advocate for themselves or any other important messages that you wanna leave the audience with.

Dr. Claire Harrison:

I think I would want the listeners to feel empowered and to feel very hopeful, this is the time where there’s a great change. We’ve been through a really difficult couple of years, but actually, we group together really well as a patient in a clinical community, and we’ve learned a lot, so trust your clinical team if you don’t trust them if there’s a problem. Move on. And don’t be afraid to do that, don’t be afraid to ask for another opinion, actually, we as clinicians like somebody else to give an opinion on our patients, that’s another thing we haven’t covered, and do connect with patient advocacy and keep up-to-date. Do you ask for a copy of your letter, don’t be afraid to ask for copies of your diagnostic information, you will properly outlive the relationship with your clinician. I will probably retire before my patients move on from my practice, so keep the information and understand it as much as you can.

Dr. Nicole Rochester:

Wonderful, thank you. So Dr. Harrison and you’ve just left us with a message of hope and a message of empowerment, and I think those two things are incredibly important, so I really appreciate you taking time with us today, and thank you so much for sharing your insights and your expertise. And I wanna thank you all for tuning in to this Patient Empowerment Network program. 

Why Is Specialized Care Important for MPN Patients?

Why Is Specialized Care Important for MPN Patients? from Patient Empowerment Network on Vimeo.

Specialized myeloproliferative neoplasm (MPN) care is an option for many patients. Dr. Kristen Pettit from Rogel Cancer Center explains various ways that specialized MPN care can benefit patients and MPN conditions that specialists are commonly trained in.

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Transcript:

Dr. Kristen Pettit:

I do think it’s important for patients to have an MPN specialist in their corner when they’re living with an MPN, that things are moving very quickly in the MPN fields in all areas, from diagnosis to risk stratification, to treatment and management over time, as well as monitoring.

So I think having someone who focuses specifically and only on MPN to is up-to-date on the most recent literature and the most recent advances, I think is an important thing, even if that’s somebody that you only maybe see either in person or virtually once a year, once every other year, or just have available if anything changes in your disease course.

So most MPNs specialists are certified in both hematology and oncology, but most focus on really all of the MPNs, these are relatively rare conditions, so most MPNs specialists will focus on ET, PV, myelofibrosis, other rare MPNs such as chronic neutrophilic leukemia, and sometimes some of the other myeloid malignancies such as myelodysplastic syndrome, for example, but your MPN doctor most likely focuses on all of those different disorders and would be able to manage your care if heaven forbid, things progress down the road from one of those MPNs to another.

How Can You Access an MPN Clinical Trial?

How Can You Access an MPN Clinical Trial? from Patient Empowerment Network on Vimeo.

How can MPN patients access clinical trials? Dr. Ruben Mesa provides tips and resources for patients to learn more about participating in an MPN clinical trial.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

See More From MPN Clinical Trials 201

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Understanding Common MPN Clinical Trial Terms

Understanding Common MPN Clinical Trial Terms

MPN Clinical Trial Safety, What Are the Protocols?

MPN Clinical Trial Safety, What Are the Protocols?

An MPN Expert Defines Clinical Trial Types

An MPN Expert Defines Clinical Trial Types


Transcript:

Katherine:                  

Dr. Mesa, let’s move on to participation. How can someone find out about what trials are available to them?

Dr. Mesa:                   

So, first and foremost, it begins with a conversation with your physician. And overall, clinical trials – the majority of clinical trials are in situations where things are not going perfectly. You know, if you’re doing well, you’re feeling well, you’re doctors a hundred percent happy with how you’re doing, then a clinical trial may or may not be an option. They are usually in a situation where things are not going as well as we would like. You have residual symptoms; you’ve only had a partial response.

If the current medicines for the disease don’t agree with you, you had side effects, or others. Now additional research for learning about these trials include many different organizations. There are disease-specific ones, like the MPN Research Foundation, MPN advocacy & Education International, MPN Hub, amongst many others. There is the broader, clinicaltrials.gov. Now, that’s a very broad site.

It is searchable. Sometimes it gives you more information than is helpful, but most things are listed on there. The Leukemia and Lymphoma Society, at LLS.org, has a specific kind of navigation function that they have for learning more about clinical trials and getting matched up with them.

But it truly starts with you and your doctor. If things aren’t working well, what are the options that I have? Is it a different option in terms of therapy? Or, if not, asking about clinical trials because clinical trials, again, will have their own upsides and downsides you and doctor will go through depending upon your situation.

Katherine:                  

What are the barriers to accessing clinical trials? Are there any?

Dr. Mesa:                   

So, first, clinical trials have, kind of, the broader logistics barriers. Frequently, you need to enroll and participate at a particular site and sometimes that site is not locally. Your doctor may or may not be participating in that trial. Some trials are only done at a single institution. So, for many, there can be a hassle factor.

You know, it’s impractical for me to be there, or be there for the frequency of visits or other pieces. So, that is one potential barrier. Overall, we hope that insurance or other coverage is not a barrier. In general, clinical trials are structured in a way to hopefully have them be financially neutral for patients.

It’s not less expensive to get your care if you’re on a trial, but it shouldn’t be any more expensive because the standard of care items are billed to your insurance as they would be normally. But if there are things that are experimental, they are included as an expense of running the trial and you’re not charged for those. Now the other barrier is, specifically, trials tend to have a specific set of eligibility for participation that are medical. It may be in a subset of patients based on any number of factors.

And there may be other limiters in terms of prior health conditions, sometimes in terms of age, sometimes in terms of how well the heart, the liver, the kidneys, or other things work. There’s both kind of a logistical piece, but then there is very specific eligibility. As a researcher, when a patient is a candidate for a clinical trial, I will have to go point by point, and sometimes there might be 50 points of disease, blood tests, and organ function – other pieces that need to be correct for participation in that trial.

It’s not to say that drug may not conceivably help that individual. It’s to say that for that specific trial, that’s what’s needed to participate in that very specific clinical trial.

So, sometimes that can lead to a bit of frustration, but it’s critical so that that trial is comparing the right group of patients so that the safety is really as great as the safety can be in the conduct of that study.

Katherine:                  

Right. What sort of questions should patients be asking their healthcare team about participating in a clinical trial?

Dr. Mesa:                   

Well, I think this discussion acts as a nice framework. So first, why should I participate in this clinical trial? Meaning, what is it about my disease that makes a different treatment option a consideration? So, why to begin with? And, if so, why this trial? What drug is it? Why does it help? If it was successful, what can I expect?

Then, what is entailed with me to participate? How frequently do I need to come? What’s involved? Is there more expenses that I can anticipate?

Again, in general, I can hopefully say no. But, of course, if you’re having to fly once a month, that, in some trials, may be covered as an expense of the trial and you’re reimbursed, but it may not. So, again, I think it starts with, medically, why does it make sense? What is involved for me? And then, really, what are those other next steps? And then, what are the alternatives? Sometimes there’s more than one clinical trial as an alternative. Sometimes there’s other options that are not a clinical trial that are an alternative to consider as well.

Katherine:                  

Before we end the program, Dr. Mesa, I’d like to get your thoughts. What message would you like to leave the audience with related to clinical trial participation?

Dr. Mesa:                   

Clinical trials are essential.

They are really the only way that we make progress in terms of developing new treatments. In the United States, less than 10 percent of patients with diseases like MPNs and cancers participate in clinical trials. And, to be honest, this really slows our ability to develop new therapies that would benefit folks. These are a very important resource.

I’ll flip it around another way – in children, where, again, we want to do everything that we can – about 80 to 90 percent of children are treated in the conduct of a clinical trial, where, again, they’re constantly pushing the envelope to try to develop better therapies.

And because of that, I think our progress comparatively, in childhood cancers, has been much faster in developing therapies than it has been in adults. So, it’s critical. It’s an opportunity.

Again, it’s very much a personal decision, but it’s something that I would strongly encourage you to consider. Again, one can begin and you are not obligated to remain on if that clinical does not, in the end, end up having the benefit that you had hoped, or if it ends up having a side effect that you prefer to not experience.

MPN Clinical Trial Safety, What Are the Protocols?

MPN Clinical Trial Safety, What Are the Protocols? from Patient Empowerment Network on Vimeo.

 Safety is a top concern for many patients considering clinical trial participation. Dr. Ruben Mesa explains the protocols put in place to minimize a patient’s risks.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

See More From MPN Clinical Trials 201

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Understanding Common MPN Clinical Trial Terms

How Can You Access an MPN Clinical Trial?

How Can You Access an MPN Clinical Trial?

An MPN Expert Defines Clinical Trial Types

An MPN Expert Defines Clinical Trial Types


Transcript:

Katherine:                  

Let’s talk about safety. What are the risks of a clinical trial participation?

Dr. Mesa:                   

So, clinical trials are structured to try to have the safety be front and center in terms of caring for patients.

So, depending upon the therapy and how much is known about that therapy will dictate the frequency in which the patient is observed. If there’s specific side effects, how are we monitoring for those side effects so that, if they are starting to occur, we can discontinue it, discontinue the drug, lower the dose, etc. So, there are some times we do accept as patients and as physicians some potential new side effects in the hope that a therapy might be more effective against the disease.

So, if it might irritate the eye, do we have eyes exams? If it might cause the heart rhythm to be abnormal in some way, do we monitor electrocardiograms? If it might cause rash, do we have exams at a certain frequency to assess for rash? Is there more blood count tests done to assess for changes in the blood counts, irritation in the liver or kidney?

So, depending upon how the drug might impact someone, it really helps to dictate what monitoring is occurring in the conduct of the study to monitor for side effects.

And then there will always be a very specific plan. Well, if a side effect occurs, what do we do? Is the drug stopped? Is the dose lowered? If it’s stopped, how long do we stop it? – usually until that side effect has recovered. And then, do we restart the drug? And, if so, do we restart it at the same dose or at a dose reduction? So, a clinical trial is guided by something that is called a protocol, which is kind of the long recipe book for exactly how that trial will work and will detail all of these things so that it can be done in a thoughtful way, but also in a consistent way, across institutions.

Katherine:                  

Mm-hmm. Well, that leads me to the next question. I’m curious to know what protocols are in place to protect patients?

Dr. Mesa:                   

So, it depends very much by each clinical trial.

There are specific protocols in that any clinical trial that is developed needs to be reviewed and approved at multiple levels through an institutional review board, which is in ethics or specifically focus on clinical trials for an institution or sometimes for a broader group. There are times that there’s additional regulatory oversight from the FDA, from the National Cancer Institute, cooperative groups, and others.

So, there’s really an entire network of things put in place. Mandatory training for physicians, nurses, and staff in terms of good clinical practices in the conduct of the study. There are specific safeguards in terms of the handling of the drugs. The pharmacist, and other safeguards in terms of you receive the drug that you’re intended to receive at the right dose, made in the right way.

Everything is heavily focused in medical practice anyway on patient safety, but you can imagine that in the conduct of a clinical trial that’s taken really to the next level in terms of trying to provide every safeguard for the patient.

An MPN Expert Defines Clinical Trial Types

An MPN Expert Defines Clinical Trial Types from Patient Empowerment Network on Vimeo.

 What are the types of clinical trials? Dr. Ruben Mesa explains the differences and discusses what patients should expect with each type.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

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MPN Clinical Trial Safety, What Are the Protocols?


Transcript:

Katherine:                  

You touched upon the various types of clinical trials and I would like to look at each one of them individually. So, let’s start with the double-blind clinical trial. What is that?

Dr. Mesa:                   

What that refers to is that neither the patient nor the physician knows which of the two comparator arms of the trial are more that a patient receives. So, with a trial, let’s say that there’s more than one way that someone can be treated. Let’s say arm A is drug X, and arm B is drug X plus drug Y, where drug Y is the experimental drug, and drug X is our standard of care. The reason they are double-blinded is that if the physician or the patient know exactly which arm they’re on, that might have an influence in terms of the physician assessing the response of the patient, the patient filling out questionnaires regarding response in symptoms.

It’s natural for us if we’re on a drug to say, “Oh, wow, you know, I automatically feel better. I’m excited about being on this,” and lead to what we call a bit of a placebo effect. Where there have been studies in the past where someone got a placebo but believed they were already feeling better even though nothing different had occurred. So, that they had somewhat kind of convinced themselves they were going to be doing better. So, the intent is, again, just to get the most objective set of response both from the physician and from the patient.

Katherine:                  

What is a randomized clinical trial?

Dr. Mesa:                   

A randomized trial means that when there is more than one arm, which treatment that a patient receives is random, is not chosen by the physician. Why that is the case is, again, we truly want to see which approach is better.

If the physician got to choose, they may inadvertently put all the sicker patients on one arm, or put all the less sick patients on one arm. In either case, it would make the value of the clinical trial less.

The value of the clinical trial, the entire reason we do them, is to try to, in the best way that we can, figure out which approach was better, whether that’s a treatment for your MPN, whether that’s figuring out whether a COVID vaccine helps to prevent to COVID, whether it’s figuring out whether a cholesterol lowering medicine is a good medicine to be on. Regardless of the reason, we want to know, is it the right way to go?

Because after that, there will be a lot of people who receive that treatment.

Katherine:                  

And finally, what is a controlled clinical trial?

Dr. Mesa:                   

A controlled clinical trial is, again – is following these same pieces where it has a comparator, where that comparator arm is sometimes also called the control, meaning that’s kind of the baseline – and, again, you’re looking to see, does that make a difference a baseline. So, let me use an MPN analogy. When ruxolitinib or Jakafi was first tested, there were no approved drugs for myelofibrosis.

So, how that worked – it was a controlled study. There was randomized placebo control. Half the group got ruxolitinib, half got placebo. After 24 weeks, people could then go on to get the ruxolitinib.

So, everyone eventually got the ruxolitinib. But, for those 24 weeks, we were able to compare what did the standard of care, which was really nothing, against ruxolitinib and saw a dramatic benefit. Now, the newer trials, now that ruxolitinib (Jakafi) is approved, ruxolitinib has been the control.

So, when there was a ruxolitinib and momelotinib trial to see if momelotinib was an effective drug, it was compared against ruxolitinib. Now, it was blinded, so that you didn’t know which of the two that you were on, but people were getting an active control. So, that is an active-controlled trial versus a placebo-controlled trial where the comparator is placebo.

Katherine:                  

What is an observational study, and how does that differ from the other clinical trials?

Dr. Mesa:                   

An observational study, as the name might suggest, is, again, where you’re observing a group of individuals, whether they start on a treatment, whether you’re trying to see how the disease behaves over a period of time.

But what it typically does not do is that you are intervening in a very specific sort of way where you are again changing how people otherwise would have been treated.

Understanding Common MPN Clinical Trial Terms

Understanding Common MPN Clinical Trial Terms from Patient Empowerment Network on Vimeo.

 Dr. Ruben Mesa explains common terminology used in MPN clinical trials, including adverse events, HIPPA, and placebos.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

See More From MPN Clinical Trials 201

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An MPN Expert Defines Clinical Trial Types

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MPN Clinical Trial Safety, What Are the Protocols?


Transcript:

Katherine:                  

Let’s move on to some common language used around clinical trials. I’ll mention a few and then maybe you could define them for the audience. The first one is, informed consent. What does that mean?

Dr. Mesa:                   

Informed consent is that what is involved with participating with a trial, what the drug is, what do we know about its safety, what you might anticipate, either in terms of side effects, whether a likely side effect or a rare side effect.

And what’s involved with you in terms of a participation, whom to call if there’s an issue. It really is an extensive document. It looks like a contract, but actually it is not.

So, informed consent is not an obligation to participate in the trial, nor does it mean that you have to stay on the trial for any length of time.

It is truly to inform you, and then you sign it, saying that you have been informed. One important concept: in the clinical trial, you are always in the driver’s seat, so that if you take – you sign the consent and you choose not to participate, you’re done then and there. If you take one dose and you don’t want to take anymore – fine. So, you’re always in the driver’s seat. It looks like a contract; it clearly is not. It is not an obligation from your side.

Katherine:                  

That’s good to know. What about standard of care?

Dr. Mesa:                   

So, standard of care is the medical language we use to how we would treat you otherwise. So, a clinical trial, by definition, is we’re trying something new.

Sometimes it’s a drug that’s never been approved, but sometimes it’s a drug that’s approved that we’re testing in a different way. Standard of care is kind of the default care that you would normally receive anyway, that is kind of the medical standard for your particular condition.

Katherine:                  

What does adverse event mean?

Dr. Mesa:                   

An adverse event means any possible side effect or event, a hospitalization or something of that nature. And then, the doctor typically attributes whether it’s related or unrelated. So, let me use an example.

If you’re on a clinical trial with a drug, but you go skiing; you fall and you break your ankle. That is an adverse event. You were hospitalized and had a broken ankle during the conduct of the study.

Now, it likely is not attributed to the trial drug, and that’ll be discussed and investigated.

But maybe it was. Maybe you felt light-headed and you passed out because of the drug you were on and you were skiing. So, again, that is a determination that your doctor makes about an adverse event. But it’s an adverse event whether it’s related to the drug or whether it has nothing to do with the drug.

Katherine:                  

And what about HIPAA? What does that mean?

Dr. Mesa:                   

HIPAA relates to – and I forget the full acronym – but really, it’s around the integrity of your patient information and that that is not able to be disclosed in a way that is either harmful to you or to individuals that really are not authorized to receive that information, which typically includes your treating team with permission – if you give permission to another healthcare provider or system, to your insurance company, et cetera.

But it’s really around both portability, I believe, in terms of your patient record, but also in terms of privacy.

Katherine:                  

A big concern for patients who may be considering participating in a clinical trial is fear that they will receive a placebo. Can you define what a placebo is for the audience?

Dr. Mesa:                   

So, a placebo means a drug that is inert. So, historically, a placebo has been, let’s say, like a sugar pill.

So, one, it is a very small minority of trials in this day and age that have a placebo. So, one, it’s almost solely in the setting of a Phase III trial. So, in a Phase I trial, everyone gets the drug. In a Phase II trial, typically everyone gets the drug. In a Phase III trial, there is typically something that it is compared against.

Now, if there’s a standard of care approach, that’s likely the comparison group.

Now, the group that starts with standard of care may well then have a period where they “crossover,” where they are treated in one way for a certain amount of time, and then get kind of the drug in question. A placebo is truly meant to be the same as kind of getting nothing. Now, in a disease like MPN, the number of placebo control trials is really very few. Sometimes a situation that they are used is where the comparator is, let’s say, trying to use two drugs – so, let’s say, the standard of care plus a new drug – versus the standard of care alone.

Now, sometimes people will take both the standard of care and a placebo so that they are, what we call, blinded. So, they don’t know which treatment arm they were on. They’re still getting treatment. They’re still getting the treatment that they would’ve anyway, but they don’t get two treatments. So, the second part is a placebo.

But anything like this, one – any trial a doctor refers you to, one should fully understand exactly how the trial works. Is it a trial with a placebo? Is it not? And then, allow that to help kinda inform your own consideration.

Is this something that I’m willing to do? Does it make sense? Is there a different approach? You know, is there a different trial that does not involve a placebo? So, I think, as physicians, we clearly understand that we try to absolutely minimize the situation where placebos are used. And when they are used, they are only used in a way that we feel that no one is getting less than at least the standard of care therapy that they would otherwise.

You know, it is unethical for there to be a placebo that really would deny patient a therapy that we otherwise know would be helpful.           

Katherine:                  

Are there other common terms that you think patients should understand and know about?

Dr. Mesa:                   

As you relate to adverse events, sometimes you would hear the term, serious adverse event, and this is sometimes to separate whether, again, as the name suggests, they are serious – and by serious, that sometimes has a threshold of requiring hospitalization, requiring a visit to the ED, emergency department – to potentially being life-threatening. Now sometimes these are associated with the disease or the medication. Sometimes, they’re unrelated. But these are ones we’re particularly sensitive of.

Again, as one looks at side effects of therapies, you’ll look at an informed consent and typically it will be a fairly long list of possible things. A relatively short list of things that we expect might happen being likely to occur, maybe can occur in greater than 20 percent of people, and sometimes some really rare things that are less likely to occur. But we also look at – when we look at a trial and look at all of the side effects that people had – were they related, were they unrelated, and were they potentially serious or not?

Understanding Clinical Trial Phases

Understanding Clinical Trial Phases from Patient Empowerment Network on Vimeo.

 What happens in each phase of a clinical trial? Dr. Ruben Mesa explains the structure of clinical trials and what MPN patients can expect when participating in a trial. 

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

See More From MPN Clinical Trials 201

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Understanding Common MPN Clinical Trial Terms

Understanding Common MPN Clinical Trial Terms

An MPN Expert Defines Clinical Trial Types

An MPN Expert Defines Clinical Trial Types

MPN Clinical Trial Safety, What Are the Protocols?

MPN Clinical Trial Safety, What Are the Protocols?


Transcript:

Katherine:                  

What is a clinical trial? Let’s start with that.

Dr. Mesa:                   

It’s a very good question. A clinical trial is a very structured way for us to be able to ask a question, whether that question is, is a new therapy safe?

Is it effective for a particular disease? Sometimes there are clinical trials that don’t involve treatments, that involve questionnaires, or other interventions, things like exercise or yoga or other things. But in general, it’s where we are having a patient do something in a structured way that we are able to then assess. Is it safe and is it effective? Is it reaching our goal in terms of trying to have an impact on that disease, whatever that is?

So, if it’s a blood pressure medicine, it’s probably about lowering the blood pressure. If it was about the COVID vaccines, did the vaccines help people from developing COVID or make COVID less severe? So, what they’re testing is variable. But the concept is the same.

It’s a very organized way for patients to be able to receive something that is closely monitored, that has been approved in advance as being a reasonable, safe, and ethical to ask patients to participate.

Katherine:                  

What are the phases of clinical trials?

Dr. Mesa:                   

So, the phases are particularly to treatment or drug use trials for developing new therapies. And they start with Phase I, which is typically the first time a drug is tested in human beings. It’s already gone testing in the lab to see whether it should work. It likely has had some animal testing to get a sense of dose and safety. But then, the first individuals who receive the drug, it’s on Phase I. What we’re really trying to understand the safety of the drug and to try to get around the dose.

There is the Phase II, typically where we’re testing a therapy in a group of people that are all similar to see what is the effectiveness of the treatment.

So, that first phase is, is the drug safe? What is the dose? The second phase is, is the drug effective? and however we define effective for that particular disease. And then, the third phase is where that new treatment is compared against how we otherwise normally would have treated the disease. So, if that’s in the setting of where we already have a drug that is approved, it’ll be compared against that drug.

If there’s never been a drug, then that comparator could possibly be a placebo, or an inactive part, or observation, or sometimes best alternative therapy the doctors can use.

There is, finally, a fourth phase. There are times that, after a drug is approved, the FDA will ask for additional information – safety information, effectiveness information – even after approval, and that’s something referred to as the fourth phase.

Clinical Trials As an MPN Treatment Option: What You Should Know

Clinical Trials As an MPN Treatment Option: What You Should Know from Patient Empowerment Network on Vimeo.

 Should you consider an MPN clinical trial? Dr. Ruben Mesa provides an overview of clinical trials—including the phases—and defines common trial terms and types. Dr. Mesa shares advice on trial participation and gives an update on the latest advances in MPN research.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

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Transcript:

Katherine:                  

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss research advances in myeloproliferative neoplasms, or MPNs, and review key information that patients should know about clinical trial participation.

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Ruben Mesa. Dr. Mesa, welcome. Would you please introduce yourself?

Dr. Mesa:                   

Thank you so much. It’s a pleasure to be here. I’m Ruben Mesa. I’m the executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson.

Katherine:                  

Great. Thank you so much for joining us today. As we move through this conversation, we’ll talk about the classic myeloproliferative neoplasms, essential thrombocythemia, polycythemia vera, and myelofibrosis. So, before we dive deeper into our clinical trial discussion, let’s talk about research advances. What are the latest developments in the field of myeloproliferative neoplasms?

Dr. Mesa:                   

There are many advances that are very important for patients to know about. First, we’re learning more about the biology of these diseases. Why do they occur? Why do they progress? Why are they different in different individuals? Indeed, the course of these diseases can be quite variable. So, these important pieces of biology are important for us to be able to better diagnose the disease, monitor the disease, and develop better therapies.

Second, I would say that there are many important new therapies that are in development. They are only able to be developed into therapies that patients can use by the process of undergoing through clinical trials. But these therapies are for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. So, a critical part, but many different scientific advances that are important and hopefully will have an important impact for patients with MPNs.

Katherine:                  

Mm-hmm. It sounds very promising. And, of course, these research advances wouldn’t be possible without patients actually participating in clinical trials. So, can you help us understand more about the trials? What is a clinical trial? Let’s start with that.

Dr. Mesa:                   

It’s a very good question. A clinical trial is a very structured way for us to be able to ask a question, whether that question is, is a new therapy safe?

Is it effective for a particular disease? Sometimes there are clinical trials that don’t involve treatments, that involve questionnaires, or other interventions, things like exercise or yoga or other things. But in general, it’s where we are having a patient do something in a structured way that we are able to then assess. Is it safe and is it effective? Is it reaching our goal in terms of trying to have an impact on that disease, whatever that is?

So, if it’s a blood pressure medicine, it’s probably about lowering the blood pressure. If it was about the COVID vaccines, did the vaccines help people from developing COVID or make COVID less severe? So, what they’re testing is variable. But the concept is the same.

It’s a very organized way for patients to be able to receive something that is closely monitored, that has been approved in advance as being a reasonable, safe, and ethical to ask patients to participate.

Katherine:                  

What are the phases of clinical trials?

Dr. Mesa:                   

So, the phases are particularly to treatment or drug use trials for developing new therapies. And they start with Phase I, which is typically the first time a drug is tested in human beings. It’s already gone testing in the lab to see whether it should work. It likely has had some animal testing to get a sense of dose and safety. But then, the first individuals who receive the drug, it’s on Phase I. What we’re really trying to understand the safety of the drug and to try to get around the dose.

There is the Phase II, typically where we’re testing a therapy in a group of people that are all similar to see what is the effectiveness of the treatment.

So, that first phase is, is the drug safe? What is the dose? The second phase is, is the drug effective? and however we define effective for that particular disease. And then, the third phase is where that new treatment is compared against how we otherwise normally would have treated the disease. So, if that’s in the setting of where we already have a drug that is approved, it’ll be compared against that drug.

If there’s never been a drug, then that comparator could possibly be a placebo, or an inactive part, or observation, or sometimes best alternative therapy the doctors can use.

There is, finally, a fourth phase. There are times that, after a drug is approved, the FDA will ask for additional information – safety information, effectiveness information – even after approval, and that’s something referred to as the fourth phase.

Katherine:                  

Let’s move on to some common language used around clinical trials. I’ll mention a few and then maybe you could define them for the audience. The first one is, informed consent. What does that mean?

Dr. Mesa:                   

Informed consent is that what is involved with participating with a trial, what the drug is, what do we know about its safety, what you might anticipate, either in terms of side effects, whether a likely side effect or a rare side effect.

And what’s involved with you in terms of a participation, whom to call if there’s an issue. It really is an extensive document. It looks like a contract, but actually it is not.

So, informed consent is not an obligation to participate in the trial, nor does it mean that you have to stay on the trial for any length of time.

It is truly to inform you, and then you sign it, saying that you have been informed. One important concept: in the clinical trial, you are always in the driver’s seat, so that if you take – you sign the consent and you choose not to participate, you’re done then and there. If you take one dose and you don’t want to take anymore – fine. So, you’re always in the driver’s seat. It looks like a contract; it clearly is not. It is not an obligation from your side.

Katherine:                  

That’s good to know. What about standard of care?

Dr. Mesa:                   

So, standard of care is the medical language we use to how we would treat you otherwise. So, a clinical trial, by definition, is we’re trying something new.

Sometimes it’s a drug that’s never been approved, but sometimes it’s a drug that’s approved that we’re testing in a different way. Standard of care is kind of the default care that you would normally receive anyway, that is kind of the medical standard for your particular condition.

Katherine:                  

What does adverse event mean?

Dr. Mesa:                   

An adverse event means any possible side effect or event, a hospitalization or something of that nature. And then, the doctor typically attributes whether it’s related or unrelated. So, let me use an example.

If you’re on a clinical trial with a drug, but you go skiing; you fall and you break your ankle. That is an adverse event. You were hospitalized and had a broken ankle during the conduct of the study.

Now, it likely is not attributed to the trial drug, and that’ll be discussed and investigated.

But maybe it was. Maybe you felt light-headed and you passed out because of the drug you were on and you were skiing. So, again, that is a determination that your doctor makes about an adverse event. But it’s an adverse event whether it’s related to the drug or whether it has nothing to do with the drug.

Katherine:                  

And what about HIPAA? What does that mean?

Dr. Mesa:                   

HIPAA relates to – and I forget the full acronym – but really, it’s around the integrity of your patient information and that that is not able to be disclosed in a way that is either harmful to you or to individuals that really are not authorized to receive that information, which typically includes your treating team with permission – if you give permission to another healthcare provider or system, to your insurance company, et cetera.

But it’s really around both portability, I believe, in terms of your patient record, but also in terms of privacy.

Katherine:                  

A big concern for patients who may be considering participating in a clinical trial is fear that they will receive a placebo. Can you define what a placebo is for the audience?

Dr. Mesa:                   

So, a placebo means a drug that is inert. So, historically, a placebo has been, let’s say, like a sugar pill.

So, one, it is a very small minority of trials in this day and age that have a placebo. So, one, it’s almost solely in the setting of a Phase III trial. So, in a Phase I trial, everyone gets the drug. In a Phase II trial, typically everyone gets the drug. In a Phase III trial, there is typically something that it is compared against.

Now, if there’s a standard of care approach, that’s likely the comparison group.

Now, the group that starts with standard of care may well then have a period where they “crossover,” where they are treated in one way for a certain amount of time, and then get kind of the drug in question. A placebo is truly meant to be the same as kind of getting nothing. Now, in a disease like MPN, the number of placebo control trials is really very few. Sometimes a situation that they are used is where the comparator is, let’s say, trying to use two drugs – so, let’s say, the standard of care plus a new drug – versus the standard of care alone.

Now, sometimes people will take both the standard of care and a placebo so that they are, what we call, blinded. So, they don’t know which treatment arm they were on. They’re still getting treatment. They’re still getting the treatment that they would’ve anyway, but they don’t get two treatments. So, the second part is a placebo.

But anything like this, one – any trial a doctor refers you to, one should fully understand exactly how the trial works. Is it a trial with a placebo? Is it not? And then, allow that to help kinda inform your own consideration.

Is this something that I’m willing to do? Does it make sense? Is there a different approach? You know, is there a different trial that does not involve a placebo? So, I think, as physicians, we clearly understand that we try to absolutely minimize the situation where placebos are used. And when they are used, they are only used in a way that we feel that no one is getting less than at least the standard of care therapy that they would otherwise.

You know, it is unethical for there to be a placebo that really would deny patient a therapy that we otherwise know would be helpful.           

Katherine:                  

You touched upon the various types of clinical trials and I would like to look at each one of them individually. So, let’s start with the double-blind clinical trial. What is that?

Dr. Mesa:                   

What that refers to is that neither the patient nor the physician knows which of the two comparator arms of the trial are more that a patient receives. So, with a trial, let’s say that there’s more than one way that someone can be treated. Let’s say arm A is drug X, and arm B is drug X plus drug Y, where drug Y is the experimental drug, and drug X is our standard of care. The reason they are double-blinded is that if the physician or the patient know exactly which arm they’re on, that might have an influence in terms of the physician assessing the response of the patient, the patient filling out questionnaires regarding response in symptoms.

It’s natural for us if we’re on a drug to say, “Oh, wow, you know, I automatically feel better. I’m excited about being on this,” and lead to what we call a bit of a placebo effect. Where there have been studies in the past where someone got a placebo but believed they were already feeling better even though nothing different had occurred. So, that they had somewhat kind of convinced themselves they were going to be doing better. So, the intent is, again, just to get the most objective set of response both from the physician and from the patient.

Katherine:                  

What is a randomized clinical trial?

Dr. Mesa:                   

A randomized trial means that when there is more than one arm, which treatment that a patient receives is random, is not chosen by the physician. Why that is the case is, again, we truly want to see which approach is better.

If the physician got to choose, they may inadvertently put all the sicker patients on one arm, or put all the less sick patients on one arm. In either case, it would make the value of the clinical trial less.

The value of the clinical trial, the entire reason we do them, is to try to, in the best way that we can, figure out which approach was better, whether that’s a treatment for your MPN, whether that’s figuring out whether a COVID vaccine helps to prevent to COVID, whether it’s figuring out whether a cholesterol lowering medicine is a good medicine to be on. Regardless of the reason, we want to know, is it the right way to go?

Because after that, there will be a lot of people who receive that treatment.

Katherine:                  

And finally, what is a controlled clinical trial?

Dr. Mesa:                   

A controlled clinical trial is, again – is following these same pieces where it has a comparator, where that comparator arm is sometimes also called the control, meaning that’s kind of the baseline – and, again, you’re looking to see, does that make a difference a baseline. So, let me use an MPN analogy. When ruxolitinib or Jakafi was first tested, there were no approved drugs for myelofibrosis.

So, how that worked – it was a controlled study. There was randomized placebo control. Half the group got ruxolitinib, half got placebo. After 24 weeks, people could then go on to get the ruxolitinib.

So, everyone eventually got the ruxolitinib. But, for those 24 weeks, we were able to compare what did the standard of care, which was really nothing, against ruxolitinib and saw a dramatic benefit. Now, the newer trials, now that ruxolitinib (Jakafi) is approved, ruxolitinib has been the control.

So, when there was a ruxolitinib and momelotinib trial to see if momelotinib was an effective drug, it was compared against ruxolitinib. Now, it was blinded, so that you didn’t know which of the two that you were on, but people were getting an active control. So, that is an active-controlled trial versus a placebo-controlled trial where the comparator is placebo.

Katherine:                  

What is an observational study, and how does that differ from the other clinical trials?

Dr. Mesa:                   

An observational study, as the name might suggest, is, again, where you’re observing a group of individuals, whether they start on a treatment, whether you’re trying to see how the disease behaves over a period of time.

But what it typically does not do is that you are intervening in a very specific sort of way where you are again changing how people otherwise would have been treated.

Katherine:                  

Are there other common terms that you think patients should understand and know about?

Dr. Mesa:                   

As you relate to adverse events, sometimes you would hear the term, serious adverse event, and this is sometimes to separate whether, again, as the name suggests, they are serious – and by serious, that sometimes has a threshold of requiring hospitalization, requiring a visit to the ED, emergency department – to potentially being life-threatening. Now sometimes these are associated with the disease or the medication. Sometimes, they’re unrelated. But these are ones we’re particularly sensitive of.

Again, as one looks at side effects of therapies, you’ll look at an informed consent and typically it will be a fairly long list of possible things. A relatively short list of things that we expect might happen being likely to occur, maybe can occur in greater than 20 percent of people, and sometimes some really rare things that are less likely to occur. But we also look at – when we look at a trial and look at all of the side effects that people had – were they related, were they unrelated, and were they potentially serious or not?

Katherine:                  

Let’s talk about safety. What are the risks of a clinical trial participation?

Dr. Mesa:                   

So, clinical trials are structured to try to have the safety be front and center in terms of caring for patients.

So, depending upon the therapy and how much is known about that therapy will dictate the frequency in which the patient is observed. If there’s specific side effects, how are we monitoring for those side effects so that, if they are starting to occur, we can discontinue it, discontinue the drug, lower the dose, etc. So, there are some times we do accept as patients and as physicians some potential new side effects in the hope that a therapy might be more effective against the disease.

So, if it might irritate the eye, do we have eyes exams? If it might cause the heart rhythm to be abnormal in some way, do we monitor electrocardiograms? If it might cause rash, do we have exams at a certain frequency to assess for rash? Is there more blood count tests done to assess for changes in the blood counts, irritation in the liver or kidney?

So, depending upon how the drug might impact someone, it really helps to dictate what monitoring is occurring in the conduct of the study to monitor for side effects.

And then there will always be a very specific plan. Well, if a side effect occurs, what do we do? Is the drug stopped? Is the dose lowered? If it’s stopped, how long do we stop it? – usually until that side effect has recovered. And then, do we restart the drug? And, if so, do we restart it at the same dose or at a dose reduction? So, a clinical trial is guided by something that is called a protocol, which is kind of the long recipe book for exactly how that trial will work and will detail all of these things so that it can be done in a thoughtful way, but also in a consistent way, across institutions.

Katherine:                  

Mm-hmm. Well, that leads me to the next question. I’m curious to know what protocols are in place to protect patients?

Dr. Mesa:                   

So, it depends very much by each clinical trial.

There are specific protocols in that any clinical trial that is developed needs to be reviewed and approved at multiple levels through an institutional review board, which is in ethics or specifically focus on clinical trials for an institution or sometimes for a broader group. There are times that there’s additional regulatory oversight from the FDA, from the National Cancer Institute, cooperative groups, and others.

So, there’s really an entire network of things put in place. Mandatory training for physicians, nurses, and staff in terms of good clinical practices in the conduct of the study. There are specific safeguards in terms of the handling of the drugs. The pharmacist, and other safeguards in terms of you receive the drug that you’re intended to receive at the right dose, made in the right way.

Everything is heavily focused in medical practice anyway on patient safety, but you can imagine that in the conduct of a clinical trial that’s taken really to the next level in terms of trying to provide every safeguard for the patient.

Katherine:                  

Dr. Mesa, let’s move on to participation. How can someone find out about what trials are available to them?

Dr. Mesa:                   

So, first and foremost, it begins with a conversation with your physician. And overall, clinical trials – the majority of clinical trials are in situations where things are not going perfectly. You know, if you’re doing well, you’re feeling well, you’re doctors a hundred percent happy with how you’re doing, then a clinical trial may or may not be an option. They are usually in a situation where things are not going as well as we would like. You have residual symptoms; you’ve only had a partial response.

If the current medicines for the disease don’t agree with you, you had side effects, or others. Now additional research for learning about these trials include many different organizations. There are disease-specific ones, like the MPN Research Foundation, MPN advocacy & Education International, MPN Hub, amongst many others. There is the broader, clinicaltrials.gov. Now, that’s a very broad site.

It is searchable. Sometimes it gives you more information than is helpful, but most things are listed on there. The Leukemia and Lymphoma Society, at LLS.org, has a specific kind of navigation function that they have for learning more about clinical trials and getting matched up with them.

But it truly starts with you and your doctor. If things aren’t working well, what are the options that I have? Is it a different option in terms of therapy? Or, if not, asking about clinical trials because clinical trials, again, will have their own upsides and downsides you and doctor will go through depending upon your situation.

Katherine:                  

What are the barriers to accessing clinical trials? Are there any?

Dr. Mesa:                   

So, first, clinical trials have, kind of, the broader logistics barriers. Frequently, you need to enroll and participate at a particular site and sometimes that site is not locally. Your doctor may or may not be participating in that trial. Some trials are only done at a single institution. So, for many, there can be a hassle factor.

You know, it’s impractical for me to be there, or be there for the frequency of visits or other pieces. So, that is one potential barrier. Overall, we hope that insurance or other coverage is not a barrier. In general, clinical trials are structured in a way to hopefully have them be financially neutral for patients.

It’s not less expensive to get your care if you’re on a trial, but it shouldn’t be any more expensive because the standard of care items are billed to your insurance as they would be normally. But if there are things that are experimental, they are included as an expense of running the trial and you’re not charged for those. Now the other barrier is, specifically, trials tend to have a specific set of eligibility for participation that are medical. It may be in a subset of patients based on any number of factors.

And there may be other limiters in terms of prior health conditions, sometimes in terms of age, sometimes in terms of how well the heart, the liver, the kidneys, or other things work. There’s both kind of a logistical piece, but then there is very specific eligibility. As a researcher, when a patient is a candidate for a clinical trial, I will have to go point by point, and sometimes there might be 50 points of disease, blood tests, and organ function – other pieces that need to be correct for participation in that trial.

It’s not to say that drug may not conceivably help that individual. It’s to say that for that specific trial, that’s what’s needed to participate in that very specific clinical trial.

So, sometimes that can lead to a bit of frustration, but it’s critical so that that trial is comparing the right group of patients so that the safety is really as great as the safety can be in the conduct of that study.

Katherine:                  

Right. What sort of questions should patients be asking their healthcare team about participating in a clinical trial?

Dr. Mesa:                   

Well, I think this discussion acts as a nice framework. So first, why should I participate in this clinical trial? Meaning, what is it about my disease that makes a different treatment option a consideration? So, why to begin with? And, if so, why this trial? What drug is it? Why does it help? If it was successful, what can I expect?

Then, what is entailed with me to participate? How frequently do I need to come? What’s involved? Is there more expenses that I can anticipate?

Again, in general, I can hopefully say no. But, of course, if you’re having to fly once a month, that, in some trials, may be covered as an expense of the trial and you’re reimbursed, but it may not. So, again, I think it starts with, medically, why does it make sense? What is involved for me? And then, really, what are those other next steps? And then, what are the alternatives? Sometimes there’s more than one clinical trial as an alternative. Sometimes there’s other options that are not a clinical trial that are an alternative to consider as well.

Katherine:                  

Before we end the program, Dr. Mesa, I’d like to get your thoughts. What message would you like to leave the audience with related to clinical trial participation?

Dr. Mesa:                   

Clinical trials are essential.

They are really the only way that we make progress in terms of developing new treatments. In the United States, less than 10 percent of patients with diseases like MPNs and cancers participate in clinical trials. And, to be honest, this really slows our ability to develop new therapies that would benefit folks. These are a very important resource.

I’ll flip it around another way – in children, where, again, we want to do everything that we can – about 80 to 90 percent of children are treated in the conduct of a clinical trial, where, again, they’re constantly pushing the envelope to try to develop better therapies.

And because of that, I think our progress comparatively, in childhood cancers, has been much faster in developing therapies than it has been in adults. So, it’s critical. It’s an opportunity.

Again, it’s very much a personal decision, but it’s something that I would strongly encourage you to consider. Again, one can begin and you are not obligated to remain on if that clinical does not, in the end, end up having the benefit that you had hoped, or if it ends up having a side effect that you prefer to not experience.

Katherine:                  

Dr. Mesa, thank you so much for joining us today. It’s been a pleasure.

Dr. Mesa:                   

Wonderful. Thank you so much for including me.

Katherine:                  

And thank you to all of our partners. To learn more about MPNs and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.

Expert Perspective: Hopeful MPN Research and Development

Expert Perspective: Hopeful MPN Research and Development from Patient Empowerment Network on Vimeo.

MPN expert and clinical researcher Dr. Abdulraheem Yacoub shares excitement about the future of MPN treatment and research, including an optimistic outlook for new approvals in the coming year. 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 
 

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How Treatment Goals Impact MPN Treatment Decisions

Advice for Choosing MPN Therapy: What’s Right for You?

Advice for Choosing MPN Therapy: What’s Right for You?

How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions?


Transcript:

Katherine:

I wanted to get your take on the future of MPN research and treatment. Are there new developments that you’re excited about and that make you hopeful?  

Dr. Yacoub:

Absolutely. So, again, I would like to take the last few minutes to advocate for the future. And the future can only come when doctors and patients and advocates work together to advance the science. We have few tools to treat patients and to help patients. We have a lot of unanswered questions. And the only way to answer them is by designing quality clinical trials, enrolling patients on trials, taking the risk, and trying to find new answers and new therapeutics. So, I always would like to advocate for patients to seek clinical trials whether with their doctor or whether they have to travel for it, and for doctors to consider that for their patients. That’s the only way to advance science.  

There are very important national and international studies going on right now. One of the – and first, I would like to emphasize is that we have had ruxolitinib (Jakafi) as the only therapy, or the first-line therapy for myelofibrosis for a decade now.  

Not everybody responds to it, not everybody responds to it for a long time. So, now we’re designing combination trials. So, there’s a few studies that we are trying to redefine, “Is ruxolitinib alone enough, or should we have a combination first-line therapy?” So, these are some of the more important questions being asked right now.  

And this is definitely one of the bigger moves in the field, is trying to redefine what is the first-line therapy for myelofibrosis. For polycythemia vera, we’re also exploring therapeutics that would reduce phlebotomy with things you can add to your medical care to reduce phlebotomy.  

So, that’s also going on. And it’s definitely a big leap forward for many of our patients. For ET, when we don’t have any actual drugs approved other than hydroxyurea (Hydrea) and anagrelide (Agrylin), we actually have trials with interferon going on.  

So, I would like to advocate for that. So, interferon succeeded and now approved for PV, but not yet for ET. We’re working on that. So, again, in every disease, we’re trying to design clinical trials to redefine what is the best treatment today.  

We’re also doing studies to understand the cancer. So, studies where patients donate their samples for research. These are very helpful, very important. And contributing to that always advances the science, and it’s low effort to the patients. So, if there’s a clinical trial that is offered to patients, I would strongly urge everybody to consider that favorably and contribute to science. 

That’s the only way we can help future patients and ourselves immediately, at moving the field forward.  

What Are the Signs of MPN Progression?

What Are the Signs of MPN Progression? from Patient Empowerment Network on Vimeo.

Dr. Abdulraheem Yacoub, an MPN specialist, explains how essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) may progress from one disease to the next, including potential signs and symptoms of MPN progression. 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 

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What Are Treatment Options for Myelofibrosis?


Transcript:

Katherine:

We have a couple of questions from the audience. This one is from Sarah. She writes, “I’ve been living with essential thrombocythemia for three years, and have been relatively stable. Of course, I’m worried about progression to PV or MF. What is my chance of progression, and what are the signs of progression?” 

Dr. Yacoub:

That’s a very good question. And unfortunately, we’re very good at describing those numbers. Unfortunately, our tools at interfering are not as good. So, in general, patients with ET, statistically speaking, have a life expectancy that is not different from their age match peers. And Sarah’s story will be not too indifferent from her sisters and her mother, in terms of what’s going to happen to her long care and her health, provided she gets good medical care. The exception to that is that there is a transformation risk. For ET we caught around a 4 percent every 10 years in which ET will actually change into a different cancer, a higher risk cancer.   

Could be MF, could be MDS, could be acute leukemia. And that will be a much more serious diagnosis. So, it’s about 4 percent in 10 years. We do have a – or we extrapolate some of the data from other cancers. So, certain mutations are more favorable, certain mutations are more risky. And we try to forecast that but worried it’s really hard to predict that since it’s such a long journey with disease. The first symptoms or the findings, when patients start suspecting that their disease has changed, is that the pattern of symptoms that they have are different.   

They often become worse. So, they have more constitutional symptoms, more tiredness, more fevers, more night sweats, losing weight, not being able to eat a full meal, abdominal distension, the spleen gets bigger.  

So, these are some of the feelings that patients can experience that lead to this. Other objective things is when the blood tests change in a less favorable way. So, for patients with ET who always run at 800,000 platelet count, if they’re suddenly 200, and that’s in the normal range, but that’s actually not good news, because the cancer changed. And this change is not favorable. So, as the doctors run routine labs, if they see the sudden change in labs, that’s also abnormal.  

If the doctor can feel that the spleen gets bigger every time, that’s also concerning. If the patients suddenly have anemia or very high white cell count or immature white cells in the blood, that’s also a concern.  

So, that’s why it’s great or important to establish a baseline symptom burden.  A baseline spleen, a baseline bone marrow biopsy with mutation analysis, so that patients have a clear reference point to where they started, and if things change, they can always go back to that point and compare.  

How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions? from Patient Empowerment Network on Vimeo.

Dr. Abdulraheem Yacoub, an MPN specialist, shares advice for patient self-advocacy and provides tips for participating in care and treatment decisions.

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 

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Transcript:

Katherine:

Dr. Yacoub, what is the role of the patient in their care? When does shared decision-making come into play?  

Dr. Yacoub:

Absolutely. Patients are the drivers and the centerpiece of their health care. And patient self-advocacy is the most important tool. So, many of our patients are young, and they will live with their cancers a lot longer than many cancer doctors will practice oncology. And they will have many doctors. Statistically, each MPN patient will have multiple doctors throughout their career. And they will hear different derivatives. And the science will change. And they will be given different counseling over the time. And their disease will change.  

And they will have different needs as they go further. So, patients being involved in their well-being and their cancer care is important from the first day. And I always tell patients, “You need to start building your village from day one.” It is not just the patient, it’s your caregivers, it’s who else can help you.  

Who else can advise you? You might want to also invest in a friend or a spouse or a child, to come to you and listen to some of those discussions so that they can advise you later on, “Why are you making different decisions?” So, we encourage patients to be very involved early on, to build their own village, and to seek care. We routinely ask for second opinions. We want patients to always hear the story and hear the same story from another doctor so that they hear the range of how we word the truth and how we word the facts.  

And this way, they can have a better perspective. So, this is now a standard. Almost all patients should have two doctors, at least, the treating doctor and one doctor who’s an MPN specialist, who would give them another twist or another perspective to their health.  

So, and that is always important. And then there are very good references and online resources for patients to tackle in, such as this seminar and other good places where patients can seek more information. They also can go to a clinical trial to find out what are the ongoing clinical trials and advancements.   

There are structured patient symposiums nationally and regionally. So, and we strongly recommend that patients seek more opinions and more help and more resources and be very engaged with this disease, especially that it is a chronic cancer, and it’s not going to – 

Katherine:

It’s not going away. 

Dr. Yacoub:

It’s just a new lifestyle. And they need to be as engaged with it as they can.   

Advice for Choosing MPN Therapy: What’s Right for You?

Advice for Choosing MPN Therapy: What’s Right for You? from Patient Empowerment Network on Vimeo.

MPN specialist Dr. Abdulraheem Yacoub reviews factors that determine which treatment is most appropriate for your essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF). 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 

Related Programs:

 
How Treatment Goals Impact MPN Treatment Decisions

How Treatment Goals Impact MPN Treatment Decisions

How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions?

Expert Perspective: Hopeful MPN Research and Development

Expert Perspective: Hopeful MPN Research and Development


Transcript:

Katherine:

As with most conditions, all patients are different, of course, and what might work for one person might not be appropriate for another. So, how do you choose which treatment is right for a patient?   

Dr, Yacoub:

Excellent. So, and that’s actually the heart of what we define as the art of practicing medicine and being patient-centric and focused. And patients already have their own wishes and their needs. And everything should start with having a discussion with patients on what is their priority, and what are they trying to achieve.  

And we do have to explain to them the tools we have, the interventions that can help them. But we also need to make sure they’re compatible with what they actually want and their goals in life. And sometimes what we doctors want is not exactly what the patients want. So, we always have to remind ourselves that patients are the drivers of their care. And they have the absolute right to be informed and to make informed decisions based on the options we advise them about.  

So, that is always a centerpiece of healthcare. And then patients – basically, we defined four pillars of care. We want to control their symptoms, we want to prevent complications, we want to modify the disease so it doesn’t transform, and we want our therapies not to have toxicities, not to have side effects that are worse than the disease.  

So, we bring that up to the table. And we also look at the patient. What are their symptoms? What did the disease cause them to be complications?  

What is the risk that their cancer is actually going to progress quickly to hurt their lives? And how serious is the therapy we’re recommending? And we need to make sure that there is a good match between what we’re offering and what the disease is manifesting. So, for example, for patients who have a lot of symptoms, but they have low-risk cancer that they can live with for a long time, we focus on symptoms. We focus on treatments that improve their symptoms.  

While with patients who have more serious diseases that are eminently life-threatening, we focus on an expedited path to a more aggressive therapy and a bone marrow transplant.  

And then we also try to match those therapies with the other patient’s wishes and needs and so forth. So, all these factors are important. We have more tools to try to prognosticate. So, prognosticate is the medical word that we use as forecasting.  

We like to forecast the disease or the cancer. We try to predict the patient’s future. Fortunately, we actually have good tools to prognosticate now. We have models or calculators that factor in patients’ features, their symptoms, their age, their blood counts, their bone marrow findings, and their DNA mutations. And it gives us a score, a risk score that can correlate with their life expectancy or their outcomes.  

And we use those tools to guide us. So, there’s actually a tool we use to help patients reach that decision. It’s an objective tool to decide how serious is this disease and how seriously we should tackle it. It’s very applicable for patients with myelofibrosis, more sort of the other lower-risk cancers.  

Katherine:

What about comorbidities? How do they fit into the treatment plan?  

Dr. Yacoub:

Very important.  

So, again, it also goes back to finding the balance between how serious is the disease, how serious is the treatment, and how will the patient’s general health tolerate and factor in the choices patients make accordingly. So, myeloproliferative neoplasms do happen in a broad range of ages. And we have children, minors with MPNs, and we have elderly patients with MPNs. And it’s a continuous spectrum. And each individual patient will have their own health concerns and their own health comorbidities and their own wishes. And we always have to make sure that we match our therapies, the disease seriousness, and the patient’s wishes, which is also stemming from their own other health battles, too.  

We cannot turn a blind eye to the other health issues going on. That plays a major factor as we choose to discuss bone marrow transplantation with patients. Because that’s when the medical comorbidities are often the first barrier to go through.  

Katherine:

Are there specific biomarkers that may affect prognosis or treatment?  

Dr. Yacoub:

Yes. So, and we’re glad that actually myeloproliferative neoplasms are actually the model in medical oncology on how predictors can tell us a lot more about the patient’s future about the prognosis. So, early on in MPNs, we’ve developed models, like the International Prognostic Scoring Systems in many different iterations. And more recently, the Molecular Based International Prognostic Scores.  

They factor in patient’s age, they factor in blood numbers, they factor in DNA abnormalities, they also factor in DNA mutations, including the common driver mutations JAK2 and CALR and MPL, as well as more novel mutations that we call higher risk mutations.  

So, based on these models, we use these tools to predict how the cancer will behave, and how to approach it. This advancement has been an application for our MPN patients for a while, way ahead of all other fields of oncology. So, we’re proud that we can give our patients this tool before all other doctors were able to. Yeah.