Tag Archive for: combination therapy

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

Related Programs:

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

Related Programs:

Understanding Common MPN Clinical Trial Terms

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.

See More From MPN Clinical Trials 201

Related Programs:

Understanding Clinical Trial Phases

Understanding Clinical Trial Phases

How Can You Access an MPN Clinical Trial?

How Can You Access an MPN Clinical Trial?

MPN Clinical Trial Safety, What Are the Protocols?

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

Related Programs:

Understanding Clinical Trial Phases

Understanding Clinical Trial Phases

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:                  

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

Related Programs:

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.

Download Guide

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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.
 
 

Related Programs:

 
How Treatment Goals Impact MPN Treatment Decisions

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.
 

Related Programs:

 
What Are Treatment Options for Essential Thrombocythemia?

What Are Treatment Options for Essential Thrombocythemia?

What Are Treatment Options for Polycythemia Vera?

What Are Treatment Options for Polycythemia Vera?

What Are Treatment Options for Myelofibrosis?

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.  

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.   

What Are Treatment Options for Essential Thrombocythemia?

What Are Treatment Options for Essential Thrombocythemia? from Patient Empowerment Network on Vimeo.

MPN specialist Dr. Abdulraheem Yacoub reviews the various treatment approaches available to patients living with essential thrombocythmia (ET).

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

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How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions?


Transcript:

Dr: Yacoub: 

So, let’s talk about essential thrombocythemia. This is among the other MPNs, the cancer with the lowest risk. Patients with essential thrombocythemia can have clots and can have bleedings. And they also often have symptoms because of their cancer.  

But they also enjoy a long life expectancy that is almost indifferent from patients who don’t have cancer provided they get good care. So, our emphasis is on focusing that their life quality is not touched by their cancer, and focusing on treating patients with symptoms, to ameliorate the symptoms and allowing them to have a decent and good quality of life. At the same time, we would like to reduce the risk of clotting and bleeding.  

And we have tools and medicines that are very effective at doing that in select patients who we define as high risk. And now there is a more clear definition of that. So, high-risk patients are patients who are over age 60 and have a JAK2 mutation, or patients who have already had a clot.  

That is not the majority of ET patients actually. The majority are not high risk. And those patients might not require therapy to reduce their platelet count. 

But for high-risk patients, we have tools to help them. So, hydroxyurea (Hydrea) is the most commonly used medicine in this setting.  

The goal of hydroxyurea is to reduce the platelet count. And we’d like to keep it under 400, sometimes under 600 under different circumstances. And that will reduce the risk of clotting and bleeding for our patients. The other option, which I also feel passionate about is interferon.  

Interferons are drugs that we’ve used for decades. They’re very effective. They’re safe in the right hands. And they do have advantages over hydroxyurea in terms of long-term safety. These are medications we can give to young patients, we can give to pregnant patients, we can give for long term without concerns of toxicity, and also they have a higher ceiling. Patients with interferon can achieve a disease control that we cannot achieve with hydroxyurea.  

And this will be beneficial long term treating those patients. So, these – yeah, and then aspirin therapy is always something we would like to include in this regimen.  

Katherine:

I was going to ask you about that. So, aspirin is still being used as a treatment?  

 Dr. Yacoub:

Absolutely. So, the standard of care is to use aspirin. Usually, one baby aspirin once a day, preferably in the morning is what we recommend. And that’s probably all the aspirin they need. We do not want them to take more than that either.  

How Treatment Goals Impact MPN Treatment Decisions

How Treatment Goals Impact MPN Treatment Decisions from Patient Empowerment Network on Vimeo.

Dr. Abdulraheem Yacoub, an MPN specialist, reviews treatment goals for patients with essential thrombocythemia (ET), polycthemia vera (PV), and myelofibrosis (MF). Dr. Yacoub goes on to explain factors that may impact treatment decisions, including the management of symptoms and side effects. 

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 Essential Thrombocythemia?

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Transcript:

Katherine:

To give our patient audience some context before we get into the specifics of MPN treatment approaches, how would you define treatment goals?  

Dr. Yacoub:

Thank you, thank you. And I always like to highlight and emphasize that unlike many of the cancer syndromes that patients deal with, myeloproliferative neoplasms are unique. 

These are chronic cancers. There’s no finish line. And this is a disease you live with. It affects every day of your life, every activity of your future life. You plan your life events accordingly. Pregnancies and marriages and trips and all of that. So, this is a chronic cancer. And as we plan therapy, we always factor that in. We would like the cancer to have the least or almost no impact on your daily life.  

Whether it’s symptoms, whether it’s disability and dysfunction and inability to perform your daily functions, whether it’s actual physical symptoms that you’re having from the cancer, or whether it’s affecting complications that are hurting your health. So, we would like to focus on all of these, the medical aspect as well as the impact of the disease to everyday symptoms.  

This is a unique feature of these cancers. And it doesn’t really exist much in other diseases.  

So, as we approach our patients, we would like to get a good assessment of the disease burden to their lives. These can be symptoms. So, we actually have very good objective tools to measure symptoms, such as the MPN-SAF. It’s an objective tool to calculate the symptoms. So, we would like to get an objective baseline of symptoms. 

Because we do want to address the symptoms, regardless of the MPN subtype. We do want to master actually the symptoms because that is what patients feel every day, and we want to affect that early in the treatment. We also would like to get a good assessment of the disease complications. Have the patient suffered a clot or a hemorrhage or symptoms because of an enlarged spleen? Or were they unable to perform certain activities? Are they able to eat? Are they losing weight?  

So, we would like to see how is the cancer also causing them immediate morbidity, and we also would like to tackle the future. So, cancers tend to get worse with time. They tend to transform into a higher risk cancer. So, as we approach any of the MPN patients, we also talk about the future risk of the cancer turning into a more aggressive form of cancer.  

So, we would like if we can, for every patient to focus on these three pillars of their care: their immediate quality of life and symptoms, their immediate complications, and their future disease progression.  

And we would like to factor in that our treatments does not add more side effects to their lives. So, that’s the fourth pillar of how we take care of patients. So, these are the basic concepts that will apply today for all patients with all three diseases.  

Some patients will have more emphasis on one or the other. But this is something in our mind as doctors who treat MPN patients.  

Thriving with an MPN: What You Should Know About Care and Treatment

Thriving with an MPN: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

 MPN specialist and researcher, Dr. Abdulraheem Yacoub, reviews factors that help guide care decisions for MPNs – essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Dr. Yaboub discusses the goals of treatment, shares tools for taking an active role in your care, and provides an update on promising new therapies for MPNs.

 
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:                  

Hello, and welcome. I’m Katherine Banwell, your host for today. Today’s program is about how to live and thrive with an MPN. We’re going to discuss MPN treatment goals, and how you can play an active role in your care.

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.

All right, let’s meet our guest. Joining me today is Dr. Abdulraheem Yacoub. Welcome, Dr. Yacoub. Would you please introduce yourself?

Dr. Yacoub:               

Hello, Katherine. And thank you very much for inviting me to participate in this very important and near and dear topic to my heart and to everything I do every day.

I’m a hematologist-oncologist at the University of Kansas. I practice hematology 100 percent of my time, and I dedicate it to patients with MPNs. I’m an active researcher through clinical trials at my own institution, as well as part of many national and international collaborations. We all strive to provide the best care and the updates for our patients. I’m also a Director of our hematology clinics in cancers at the University of Kansas, and I’m an Associate Professor of Medicine at the University of Kansas.

Katherine:                  

Well, thank you so much for taking time out of your very busy schedule to join us today. We appreciate it.

Dr. Yacoub:               

Absolutely, my pleasure.

Katherine:                  

To give our patient audience some context before we get into the specifics of MPN treatment approaches, how would you define treatment goals?

Dr. Yacoub:               

Thank you, thank you. And I always like to highlight and emphasize that unlike many of the cancer syndromes that patients deal with, myeloproliferative neoplasms are unique.

These are chronic cancers. There’s no finish line. And this is a disease you live with. It affects every day of your life, every activity of your future life. You plan your life events accordingly. Pregnancies and marriages and trips and all of that. So, this is a chronic cancer. And as we plan therapy, we always factor that in. We would like the cancer to have the least or almost no impact on your daily life.

Whether it’s symptoms, whether it’s disability and dysfunction and inability to perform your daily functions, whether it’s actual physical symptoms that you’re having from the cancer, or whether it’s affecting complications that are hurting your health. So, we would like to focus on all of these, the medical aspect as well as the impact of the disease to everyday symptoms.

This is a unique feature of these cancers. And it doesn’t really exist much in other diseases.

Katherine:                  

That’s helpful to understand as we move through today’s program. And we’re going to cover the three classic MPNs, polycythemia vera, essential thrombocythemia, and myelofibrosis.

So, for the person who has one of these conditions, can you help us understand the treatment approaches for each? Let’s start with essential thrombocythemia or ET.

Dr. Yacoub:               

Excellent. So, I’m going to start with some general concepts. So, as we approach our patients, we would like to get a good assessment of the disease burden to their lives. These can be symptoms. So, we actually have very good objective tools to measure symptoms, such as the MPN-SAF. It’s an objective tool to calculate the symptoms. So, we would like to get an objective baseline of symptoms.

Because we do want to address the symptoms, regardless of the MPN subtype. We do want to master actually the symptoms because that is what patients feel every day and we want to affect that early in the treatment. We also would like to get a good assessment of the disease complications. Have the patient suffered a clot or a hemorrhage or symptoms because of an enlarged spleen? Or were they unable to perform certain activities? Are they able to eat? Are they losing weight?

So, we would like to see how is the cancer also causing them immediate morbidity, and we also would like to tackle the future. So, cancers tend to get worse with time. They tend to transform into a higher risk cancer. So, as we approach any of the MPN patients, we also talk about the future risk of the cancer turning into a more aggressive form of cancer.

So, we would like if we can, for every patient to focus on these three pillars of their care: their immediate quality of life and symptoms, their immediate complications, and their future disease progression.

And we would like to factor in that our treatments does not add more side effects to their lives. So, that’s the fourth pillar of how we take care of patients. So, these are the basic concepts that will apply today for all patients with all three diseases.

Some patients will have more emphasis on one or the other. But this is something in our mind as doctors who treat MPN patients, we try to balance all these three pillars for every patient. So, let’s talk about essential thrombocythemia. This is among the other MPNs, the cancer with the lowest risk. Patients with essential thrombocythemia can have clots and can have bleedings. And they also often have symptoms because of their cancer.

But they also enjoy a long life expectancy that is almost indifferent from patients who don’t have cancer provided they get good care. So, our emphasis is on focusing that their life quality is not touched by their cancer, and focusing on treating patients with symptoms, to ameliorate the symptoms and allowing them to have a decent and good quality of life. At the same time, we would like to reduce the risk of clotting and bleeding.

And we have tools and medicines that are very effective at doing that in select patients who we define as high risk. And now there is a more clear definition of that. So, high-risk patients are patients who are over age 60 and have a JAK2 mutation, or patients who have already had a clot.

That is not the majority of ET patients actually. The majority are not high risk. And those patients might not require therapy to reduce their platelet count.

But for high-risk patients, we have tools to help them. So, hydroxyurea (Hydrea) is the most commonly used medicine in this setting.

The goal of hydroxyurea is to reduce the platelet count. And we’d like to keep it under 400, sometimes under 600 under different circumstances. And that will reduce the risk of clotting and bleeding for our patients. The other option, which I also feel passionate about is interferon.

Interferons are drugs that we’ve used for decades. They’re very effective. They’re safe in the right hands.

And they do have advantages over hydroxyurea in terms of long-term safety. These are medications we can give to young patients, we can give to pregnant patients, we can give for long term without concerns of toxicity, and also they have a higher ceiling. Patients with interferon can achieve a disease control that we cannot achieve with hydroxyurea.

And this will be beneficial long term treating those patients. So, these – Yeah, and then aspirin therapy is always something we would like to include in this regimen.

Katherine:                  

I was going to ask you about that. So, aspirin is still being used as a treatment?

Dr. Yacoub:               

Absolutely. So, the standard of care is to use aspirin. Usually, one baby aspirin once a day, preferably in the morning is what we recommend. And that’s probably all the aspirin they need. We do not want them to take more than that either.

Katherine:                  

And you mentioned using interferons for ET. That’s something that you would also use for polycythemia vera. Yes?

Dr. Yacoub:               

Absolutely. So, the same principles will apply to polycythemia vera. We would like to treat the higher-risk patients more aggressively. Hydroxyurea and interferon are also the first-line therapies in these patients.

The good news in 2022 is that we actually finally have an FDA-approved interferon for our patients. Finally, after 50 years of using interferon, now, we have an FDA approval. So, the new interferon, ropeginterferon alfa-2b is a medication that was studied prospectively in Europe, and it has been approved and in clinical use in Europe under the brand name Besremi.

And this year, it was approved in the US for patients with polycythemia vera, which is a great achievement for the medical field and a great tool to help our patients. We have used other brands off-label in the past, but it’s glad now to get this confirmation from the FDA that this is a standard of care for all patients.

And then beyond that, ruxolitinib or Jakafi, is also approved as a second-line option in patients who have had hydroxyurea as their first line.

So, these are the medicines we use for polycythemia vera. We also use therapeutic phlebotomy. And the goal in high-risk polycythemia vera, or actually in all patient polycythemia vera, is to reduce their hematocrit.

And we want it under 45 percent every day of the year. And we use the tools that we just discussed phlebotomy and medicines to achieve that, in addition to aspirin. So, that’s how PV is more unique than ET. Yes.

Katherine:                  

And since myelofibrosis is a progressive condition, I imagine it’s more difficult to manage. So, what else is available for patients with myelofibrosis?

Dr. Yacoub:               

Correct So, myelofibrosis is the higher end of this spectrum of cancers.

It is a cancer that is associated with much higher symptom burden and impact on daily life. It is also associated with low blood counts, and some patients will require transfusions. It’s a major morbidity to our patients. And in addition, it’s a cancer that is associated with shortened life. So, patients with myelofibrosis will not live as long as their health would have allowed them. And some of them will live actually a much shorter life than they want or deserve.

So, myelofibrosis treatment requires a lot more considerations. So, for patients who are in good health, who have a cancer that is more aggressive, that would be imminently impacting their longevity, we start a discussion about a curative role of allogeneic stem cell transplantation very early in their course.

Because bone marrow transplantation can be curative, and those patients can live a long life after a successful transplant. So, this is a treatment modality that should be brought up very early for patients with higher risk myelofibrosis. There are approved JAK inhibitors, ruxolitinib and fedratinib (Inrebic). And we know that Ruxolitinib which has been approved for over 10 years can improve symptoms, can improve the spleen volume, can actually prolong lives for patients on it, and also makes the transplant more successful.

So, we should be offering that to the appropriate patients also early in their diagnosis, in a strategy where, in addition to that, we get them to a transplant. Fedratinib is approved in that setting. And we are very optimistic that by the end of this calendar year, we will have two other JAK inhibitors approved.

So, we look forward to those two drugs. Momelotinib and pacritinib for patients with special disease features.

[Editor’s Note: As of February 28, 2022, pacritinib (Vonjo) has been approved for the treatment of myelofibrosis patients with severe thrombocytopenia.]

And hopefully, by the end of this year, we will have a list of JAK inhibitors that we can choose from, which is great news for our patients.

Katherine:                  

Oh, we’re still fighting.

Dr. Yacoub:               

Yes, absolutely.

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 is 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.

Katherine:                  

That’s excellent. 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 wellbeing 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.

Katherine:                  

Absolutely. 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.

Katherine:                  

Right. We have another question. This one from Victor. He says, “I was diagnosed with PV in 2018. And I’ve been treated with hydroxyurea. Recently, I’ve been very fatigued. I want to exercise, but I don’t have the energy to do much. Do you have any advice for boosting my energy?”

Dr. Yacoub:               

That is a very good question and very common question. So, the causes for fatigue in adults, in general, so many. And adding PV to that adds a few other reasons why one would be more fatigued. So, assuming that Victor follows with his doctor, and his primary care doctor has systematically went through all the possible causes for fatigue, and those were addressed.

Now that PV specific causes, A). Hydroxyurea can cause fatigue. So, maybe it’s the hydroxyurea dose. And that’s a side effect. And maybe that’s not the best medicine for him. B). Polycythemia vera can cause fatigue. Maybe we’re not controlling it enough. Maybe we need to dial up the dose of the medicine or dial down the dose of the medicine accordingly. And then there’s also the iron deficiency which we induce with PV and phlebotomy.

And whether we actually have taken Victor to become very low on iron, and that can cause fatigue. So, we have to evaluate the treatments, the disease, and the side effects of the interventions we’ve done. And those are the polycythemia vera specific factors that can add to the fatigue.

Katherine:                  

Here’s another question from the audience. This is from Sandy. She writes, are MPNs hereditary? Should my children or siblings be aware of their risk?

Dr. Yacoub:               

All right. Well, the answer to that question changed many times over the last 10 years. So, the answer changed from absolutely not, to very possibly maybe over the years. So, although we don’t think of cancers as inherited, it’s not passed from one parent to their children. But MPNs tend to run in families. And for 11 percent of patients with MPN, and that number has also increased over the years, have actually a first-degree family member with MPN. That is a big coincidence, it’s almost too high to be a coincidence. So, we are realizing that there is genetic makeup or clustering that can cause MPNs to happen more often in certain families.

So, how does this apply to patients? So, if a patient has MPN, that does not mean that their children or siblings will get MPN, it just means they’re more likely than the other people to have MPN, just because they all share the same genetic makeup. And they should be made aware. And they should maintain good health care and maintain the relationship with a primary and have routine labs and all that. But not necessarily that they will get cancer. This still is a very rare disease, and 11 percent of a rare disease still is a small number.

Katherine:                  

Thank you for answering those patient questions. I appreciate it.

Dr. Yacoub:               

My Pleasure.

Katherine:                  

And to our patients, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them on future programs.

So, Dr. Yacoub, as we close out our program and our conversation, 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 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 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 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.

Katherine:                  

Seems like there’s a lot of progress in the field.

Dr. Yacoub:               

A lot of progress. I look forward to future events. I’m going to have a lot more tools to discuss. Hopefully, by this time next year, we’re going to have four JAK inhibitors, injectables for PV, interferon for ET, and a lot more things to go over.

Katherine:                  

That’s wonderful. Dr. Yacoub, thank you so much for taking the time to join us today.

Dr. Yacoub:               

You’re welcome. And it’s my pleasure. I feel passionate about this. And I’m happy to help.

Katherine:                  

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

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan? from Patient Empowerment Network on Vimeo.

Considering a clinical trial? Dr. Omar Nadeem, a myeloma specialist, shares advice for talking to your doctor about trials, including key questions to ask your physician about proposed treatments.

Dr. Omar Nadeem is the Clinical Director of Myeloma Cellular Therapies Program and Director of Myeloma and Plasma Cell Pathways at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem, here.

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Myeloma Treatment: When Should a Clinical Trial Be Considered? 


Transcript:

Katherine:

As ASH comes to a close, it’s always important to remember that these research advances wouldn’t be possible without patients participating in clinical trials. So, for patients who may be thinking about a clinical trial, when should they consider a trial and what should they be asking their doctor about?

Dr. Nadeem:

Those are great questions and very relevant questions. I think clinical trials come in many baskets. They come in the trials I just described, which are looking at established combinations and then looking to see if the addition of another agent, which is FDA approved, could lead to better results. So, those are some examples of trials where you’re trying to really advance the field by using what we already have available and studying it in either different phases of myeloma therapy or in different combinations.

Those types of trials, I think, are always very important and useful, and from a patient perspective, it should alleviate that anxiety of going on to a study that doesn’t have a track record, per se. And a lot of those trials are done in the newly diagnosed, or the first relapse setting, etcetera.

When you’ve had multiple relapses, though, we know that the disease is still not curable. So, you start to see the benefit of each treatment become shorter and shorter as patients go through their myeloma therapy, and that’s where some of these newer, exciting – especially immunotherapy drugs that are currently under study really, really are promising.

So, I think from a patient perspective, a lot of times that discussion – you’re looking at an agent that’s approved but they might not have the efficacy that we’re seeing in some of the studies.

And I think you have to discuss with your physician at that time to see whatever the clinical trial that we’re discussing or thinking about for a particular patient, what is different about it? Why is it something that they would be thinking about for their individual case? Then really, what is the expectation?

I think what we’re seeing now with all these updated results is that some of these response rates, for example, with bispecific antibodies, which is a form of immunotherapy that we’re studying quite a bit in myeloma, they look twice as good if not three times as good as some of these single agent drugs that were FDA-approved.

So, even though you might want to get the true and tested that’s been studied and cleared, the results that we’re seeing with some of these studies are so much better. So, that’s how the field moves forward. So, I think the discussion with your primary physician is key to see which particular trial, is one available, and two, what they think might be best for that particular situation.

The Latest in Myeloma Research: Updates from ASH 2021

The Latest in Myeloma Research: Updates from ASH 2021 from Patient Empowerment Network on Vimeo.

Myeloma specialist, Dr. Omar Nadeem, shares promising research advances in myeloma from the 2021 American Society of Hematology (ASH) annual meeting. Dr. Nadeem discusses the future of personalized medicine for myeloma, as well as positive results from a clinical study on quadruplet therapy.

Dr. Omar Nadeem is the Clinical Director of Myeloma Cellular Therapies Program and Director of Myeloma and Plasma Cell Pathways at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem, here.

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Transcript:

Katherine:

Personalized medicine for myeloma is slowly becoming more of a reality for patients. Can you provide an update in testing in myeloma? Are there specific markers that you’re looking for when considering patient care?

Dr. Nadeem:

So in multiple myeloma, right now the only targeted therapy that’s in development is looking at venetoclax (Venclexta), and that’s in patients that have the t(11;14) translocation.

So, this has been studied for a while, both as single agent and in combinations and the big BELLINI study, which is looking at it in combination with bortezomib (Velcade) and dexamethasone (Decadron), really has had a lot of buzz over the last few years because there was a toxicity signal with the venetoclax arm.

But now with, again, updated results, etcetera, you’re starting to look to see which are the patients that benefited and which are the patients that didn’t.

And it’s becoming very, very clear that patients that have the t(11;14) translocation tend to benefit tremendously with the combination of venetoclax and bortezomib and dexamethasone. It’s really the patients that don’t have t(11;14) or high BCL2 expression, which is something that they’re also studying, those are the patients that didn’t benefit.

So, really fine tuning that to that particular population and using a combination like that is, I think, an example of where things are headed in myeloma. However, outside of that right now with where things stand, we don’t have targeted therapy to that extent beyond that.

Katherine:

Dr. Nadeem, with the ASH meeting closing out 2021, what are you excited about in myeloma research right now?

Dr. Nadeem:

We’re seeing very impressive results with using quadruplet therapies for newly diagnosed multiple myeloma patents. So, they get a combination of a CD38 monoclonal antibody like daratumamab (Darzalex), and then combining it with our typical agents. So immunomodulatory, drugs, proteasome inhibitors, and steroids. So, an update at this meeting with the phase-2 GRIFFIN trial, which was presented by my colleague Dr. Jacob Laubach, basically giving an update after 24 months of maintenance therapy.

This trial looked at a combination of dara plus RVD, which is lenalidomide, bortezomib, and dexamethasone, with transplant and maintenance, for patients with newly diagnosed myeloma. And what we’ve seen with each update of this study, that the response rates with the quadruplets are significantly better with the triplet. And more notably, we’re seeing very high rates of minimal residual disease negativity in favor of the quadruplet, which usually translates into a greater prognosis for patients.

So, median PFS is still not reached for this particular study, but you can start to see now that the curves are starting to separate and hopefully with longer follow up, we’ll see even a clearer result showing that patients that receive a quadruplet therapy at the newly diagnosed phase of their myeloma therapy benefit tremendously. So, this was a really important update at ASH this year.

Updates in CAR T-Cell Therapy for Myeloma From ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021 from Patient Empowerment Network on Vimeo.

Myeloma specialist, Dr. Omar Nadeem, shares the latest updates in CAR T-cell therapy from the 2021 American Society of Hematology (ASH) annual meeting. Dr. Nadeem discusses long-term study results and optimism for the future of CAR T-cell therapy.

Dr. Omar Nadeem is the Clinical Director of Myeloma Cellular Therapies Program and Director of Myeloma and Plasma Cell Pathways at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem, here.

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Transcript:

Dr. Nadeem:

My name is Omar Nadeem, and I’m at the Dana Farber Cancer Institute in Boston, Massachusetts. I’m an instructor of medicine at Harvard Medical School, and I direct the myeloma cellular therapies program at Dana Farber.

Katherine:

Dr. Nadeem, you’ve joined us from the American Society of Hematology Meeting in Atlanta. Can you share any highlights in myeloma from the meeting?

Dr. Nadeem:

Yeah, it’s a very exciting time in myeloma therapeutics. We’re seeing a lot of new agents that are being reported at this meeting, showing very promising results.

Then we’re also fine tuning the way we treat myeloma patients by looking at different combinations in all lines of therapy, whether it be front-line or relapsed setting, to try to really understand which treatments are the best and then also more importantly, which treatments do we need to continue patients on, etcetera as they’re going through their myeloma journey. So, lots of updates with important trials at this meeting so far.

Katherine:

We’re hearing a lot about the promise of CAR T-cell therapy. Is there any research news in CAR T-cell for myeloma treatment?

Dr. Nadeem:

Yeah. So, we’ll have a presentation later today, actually, updated results of the CARTITUDE-1 study, which is looking at cilta-cel, which is an anti-BCMA directed CAR-T cell product.

And this trial is a phase-1/2 study looking at some patients with relapse in refractory multiple myeloma that has been reported previously to have a very, very high response rate and very high rates of MRD negativity.

So at this meeting, with just longer follow-up, which is what we’re looking for in terms of how long these responses last, we’re starting to see that the median duration of response is now almost 22 months, which is very impressive looking at the data and comparing it to some of the other CAR-T products that are either under study or the one that’s currently approved.

So, that looks very promising. And also notably, we had some concerns initially about toxicity with this particular product. But that really hasn’t been seen with longer follow-up. So, we’re not seeing a toxicity signal, particularly as it relates to neurological toxicity, with the longer follow-up. So, that presentation will be later today. We look forward to seeing the updates, but so far this looks very encouraging and this is what we anticipate to be the next product that’s available in the market for myeloma.