Tag Archive for: hematocrit

Can Bone Marrow Return to Normal After CLL Treatment?

Can Bone Marrow Return to Normal After CLL Treatment? from Patient Empowerment Network on Vimeo.

Is it possible for chronic lymphocytic leukemia (CLL) patients to achieve normal bone marrow after CLL treatment? Expert Dr. Ryan Jacobs explains MRD-undetectable status and the typical time period to deep CLL remission.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in chronic lymphocytic leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

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Transcript:

Lisa Hatfield:

This patient is asking, upon completion of venetoclax (Venclexta) and obinutuzumab (Gazyva) and achieving MRD-undetectable status, how long does it take your bone marrow to achieve improved hemoglobin, hematocrit platelets, white blood cells? And does it always return to normal? And I might add in there just any kind of treatment, does the bone marrow typically return to “normal”? And how long does that take?

Dr. Jacobs:

So the majority of patients treated in the first-line setting and actually in the relapse setting with a combination of venetoclax and obinutuzumab, will have their CLL go into such a deep remission that we cannot detect it in 1 out of 10,000 cancer cells. So that is called MRD-undetectable. Those patients are usually also in complete remission, which means if you look at the bone marrow, you’re not going to see any CLL there. So the majority of patients have their counts normalized while they’re still on the venetoclax. You take it for a year. The complete remission is usually achieved before therapy is completed. And what little, if any CLL is in the bone marrow is not causing a drop in the counts. Now, of course, patients can have the toxicity-reduced counts. And if that’s the case, if it’s a toxicity issue, then it should resolve when you stop treatment. So I would say, usually it does return to normal, if not all…when they’re on therapy, then after therapy. If it’s a relapsed patient that’s seen a lot of therapies though, the bone marrow might never return to normal. 

Lisa Hatfield:

How far out are we from curative therapies for CLL patients with the tougher prognostic indicators?

Dr. Jacobs:

So I think curative is an interesting question, and it can mean different things to different people. But we’ve already shown at the most recent American Society of Hematology meeting, when they looked at the average life expectancy of patients without CLL, since the time that ibrutinib (Imbruvica) got approved and then now CLL patients, the survival curves are overlapping. So as of now, it looks like with our newer treatments that a CLL patient should reasonably expect to live a normal life expectancy. Does that mean cure? Well, if by cure you mean, does the disease go away forever with one treatment? We still don’t think we have that therapy for most patients. But we’ll see as we get longer and longer follow-up with some of these newer agents is there are going to be a proportion of patients that never relapse, that ibrutinib is going to have the longest follow up because it was the first one. I was just looking at a poster at the European Hematology Association meeting where they’ve followed patients seven, eight years out and more than half have still not progressed that got ibrutinib as a first-line therapy. So it’s reasonable to think that maybe some will never progress.


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How Are ET, PV and Myelofibrosis Monitored?

How Are ET, PV and Myelofibrosis Monitored? from Patient Empowerment Network on Vimeo.

MPN specialist and researcher Dr. Joseph Scandura reviews tools that are used to monitor patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), including routine blood work and symptom management

Dr. Joseph Scandura is an Associate Professor of Medicine and Scientific Director of the Silver MPN Center at Weill Cornell Medicine. Learn more about Dr. Scandura.

 

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Transcript:

Katherine Banwell:

I would imagine monitoring patients is different for each of the MPNs. So, how are patients typically monitored over time, and let’s start with essential thrombocythemia?  

Dr. Scandura:

Yeah. I think – again, it’s similar. You know, what’s near-term, what’s long-term? And so, in all of these diseases, thrombosis risk is a near-term risk. That’s something that I am monitoring in certain ways to help mitigate that risk. In ET and PV, I approach them similarly. Blood counts are certainly – these are diseases of the blood forming system. Certainly, monitoring blood counts I find helpful. But the reality of it is, in ET, there is not a clear linkage between blood counts and risks.  

And so, I like to keep the platelet count near normal if I can. But I also recognize that it may not be worth suppressing all of the blood counts to achieve that landmark, because it’s not clear that that’s really reducing the risk any more than just having somebody on a medication that helps control the blood counts. In polycythemia vera, different blood counts are very important. The red blood cells are kind of like part of the clotting risk. We know from clinical trials that keeping the red blood cell parameters within certain ranges reduces the risk of clotting. And so, what I monitor in polycythemia vera is the hematocrit. In women, I like to keep it below 42. In men, I like to keep it below 45.  

But I don’t just – I’m not a slave to the hematocrit. I am keeping an eye on the other blood counts and the other red blood cell parameters. So, for instance, what’s the size of the red blood cells? That tells me a little bit about what’s going on in the blood formation for that patient. And what’s the number of red blood cells? So, sometimes people can have very small red cells, because they’re a little iron-deficient and have a huge surplus of the number of red blood cells. And that tells me a little bit about how their blood forming system is responding to therapy.  

Iron deficiency in polycythemia vera is very prominent. I personally believe it’s a very major driver of symptoms in patients who are receiving phlebotomy as part of their care. And it’s something that I monitor and really counsel patients on. My goal is to make phlebotomy independent, but it can take a while.  

Everybody starts out iron-deficient, and then we take iron out of their body through blood with the phlebotomy. And that makes them more iron-deficient.  

Katherine:

Right. 

Dr. Scandura:

I monitor symptoms from patients, and sometimes that can tell me that their disease needs to be – their treatment needs to be tweaked a little bit, even something as simple as aspirin. People can sometimes have burning in the skin or itching that is sometimes responsive to changing the aspirin dose or how it’s given, once a day versus twice a day.  

And that simple thing can be a big change for a patient who’s kind of, literally, climbing out of their skin or wishing they could and to try and find something that is helping.   

I had a patient the other day. He had COVID. I said, “Oh, you should probably get this medication.” Do you have your primary care physician? Who’s taking care of you?” And he goes, “Well, to be honest with you, you’re my guy.” And so, it’s true. I see this patient a lot. And so, sometimes they forget. If I’m not paying attention to their blood pressure, the risks or treatment of diabetes, cholesterol, lipids, their screening programs for mammogram or colonoscopy, health maintenance issues, I do keep an eye on that in patients, because I do think it’s a part of the MPNs.  

I think that there are excess risks for patients for some of these factors. Certainly, if you think of it as three strikes, they get a strike for having an MPN. I don’t want them to have any other strikes. So, diabetes, hypertension, those are strikes that I can potentially, at least, treat or refer them to somebody to help comanage with me. And so, that’s kind of my general approach. 

Katherine:

What about patients who have myelofibrosis? Are they monitored more closely? 

Dr. Scandura:

Yeah, I think it depends a little bit on the patient. Patients with early myelofibrosis often don’t have any symptoms or near-term risks much different than those from ET or PV. As the disease can progress, then some of these patients have more profound problems with symptoms, which I may be trying to find a solution to make them feel better. And also, blood counts can become more of an issue.  

Transfusions in some patients who are very high white blood cell count, the spleen is often quite enlarged. Although, in my experience, most patients aren’t really bothered by the size of their spleen as the physicians are. But it is something where I think, on average, they’re monitored a little bit more closely to quite a bit more closely depending on the patient. 

Katherine:

What happens if someone suddenly has a change in blood counts? What do you do? 

Dr. Scandura:

Yeah. I mean, repeat it. That’s the first thing. Also, check what’s going on. It’s not uncommon in patients with MPNs that I’ll see them and the counts are a little bit out of whack, the white count is much higher than it’s been, and questioning them. “Oh, yeah. I had X, Y, or Z last week or the week before.” It used to be a upper respiratory tract infection, or they had a minor surgical procedure.  

And sometimes the responses to these things can be accentuated in patients with MPNs. And so, if that’s what of this story, I certainly would repeat it and let things calm down a little. And that’s often all it is. I’m much more of a monitor of the trends. So, one-time measure doesn’t generally excite me. It might make me want to have a follow-up a little more – in a shorter period of time. Of course, it depends on what the change is. But, for most of the changes that we observe, they’re relatively minor. And I will monitor them over time.  

If I see a trend where something is progressively increasing or decreasing over time, then I start thinking about what else is going on. And that’s always in the context of what’s going on with the patient. How are they feeling? What’s their physical exam like? What are the other laboratory values like?  

Katherine:

When is a bone marrow biopsy necessary? 

Dr. Scandura:

I would say a bone marrow biopsy is absolutely necessary at the time of diagnosis. I personally do not routinely monitor by bone marrow biopsy unless it’s part of a clinical trial.  

But I do perform a bone marrow or want to look at the bone marrow morphology if there is one of these changes or at least a trend that I want a little bit more information about. And so, if – or if it’s been a very long time since somebody has had a bone marrow. If it’s been five or ten years, then sometimes I may recommend we look just so we can collect a little bit more up-to-date information.  

But I don’t routinely do a bone marrow, but I will do it if there are laboratories that are kind of trending in the wrong direction, there’s symptoms, there’s physical findings that I’m just not sure about. And I think it would help me be more sure as to what’s going on and be able to discuss that with the patient. Sometimes, just to say, “Hey. Look, we were worried about this, but the bone marrow looks really good.”  

An Overview of ET, PV and MF Treatment Options

An Overview of ET, PV and MF Treatment Options from Patient Empowerment Network on Vimeo.

Treatment for essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) can vary greatly. Dr. John Mascarenhas breaks down the treatment types and the goals of treatment for each type of myeloproliferative neoplasm (MPN).

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

Depending on the patient, it seems like ET or PV may be easily managed. So, how are they treated? Let’s start with essential thrombocythemia or ET.

Dr. Mascarenhas:       

So, ET is a disease in which first and foremost, we’re trying to reduce the risk of thrombosis, clotting, and/or hemorrhage bleeding. So, typically, ET patients are risk stratified by low risk or high risk.

It’s almost simply based on their age, whether they’ve had a clot in the past, and some systems now even incorporate other factors like mutation status. And, you tailor the treatment based on their risk score. So, low risk ET patients don’t necessarily need to be treated. They can be followed expectantly and watched. The height of the platelet count does not predict thrombotic risk. So, we don’t treat the platelet count per se. A high-risk patient is at high risk for clotting. So, these patients almost invariably are getting aspirin at a baseline, and they are often on cytoreductive therapy. And sometimes, that is chemotherapy like hydroxyurea. Sometimes it’s a non-chemotherapeutic option and like anagrelide, and sometimes it’s a biologic therapy like interferon alfa either 2a, Pegasys, or 2b ropeginterferon. And, these are therapies that have rationale, that have clinical data, that have demonstrated reduction in risk of clotting, which again is the reason why we treat high-risk ET patients.

Katherine Banwell:                  

And, what about PV, polycythemia vera?

Dr. Mascarenhas:     

So, in polycythemia vera, it’s similar to ET. We risk stratify patients low and high risk based on age and clotting histories. And whether you’re low or high risk, we give PV patients aspirin or at least once daily, and we look to keep their hematocrit below a threshold of 45 percent. And sometimes in women, we even go lower, to 42  percent. But the idea is that controlling the hematocrit, which is one of the red blood cells indices, you reduce the risk of having clots, and that’s been shown actually many years ago and reinforced in a very well-known study called the CYTO-PV study in Italy documented that if you keep the hematocrit less than 45 percent, so, stringent control versus allowing for less stringent control between 45 to 50, that you reduce by fourfold the number of cardiovascular events that can occur.

So, we know that controlling the hematocrit is important, and that can be done, again, with hydroxyurea, interferon, and ruxolitinib.

The JAK2 inhibitor has also proved specifically for patients who had an intolerance or refractory hydroxyurea, but also importantly as a drug that can address, probably better than most drugs in this field, the symptom burden that could be problematic for some of those patients. But, it’s really about controlling the hematocrit.

Katherine Banwell:                  

Yeah. Since myelofibrosis is a progressive condition, I imagine that makes it more difficult to manage. So, what else is available for patients with myelofibrosis?

Dr. Mascarenhas:       

The first line of treatment is typically a JAK inhibitor, although I would say that there are a subset of patients – well, there are patients we sometimes meet that have very low risk disease. They don’t have those clinical variables we discussed before that could uptick their risk score, and some of those patients can be watched.

And interestingly, there are a subset of patients that can have an indolent or slow form of the disease where they don’t have aggressive changes in their disease, their blood counts, their symptoms, their spleen, and don’t need immediate treatment. Most patients would benefit from a JAK inhibitor, although there are a subset of patients where their issue is less simple in spleen burden and it’s more anemia.

So, we take those patients where anemia’s the focus, we look at their erythropoietin level, which is their endogenous hormone level that regulates red blood cell production. If it’s low, we give them a lab-based form of erythropoietin, something called Procrit or Aranesp. If it’s high, we will move on. We can use a drug called danazol, which is a synthetic male androgen which can improve hemoglobin levels in 20 to 40 percent of patients. Or, we can use a drug called lenalidomide, which is an immunomodulatory drug. And, more recently, there’s a drug in testing called to luspatercept, which is an active activin receptor ligand trap. So, there is a growing armamentarium of drugs that can be used to try to alleviate the anemia which is present and can be a significant issue in about a quarter of patients with myelofibrosis upfront at time of diagnosis or about 75  percent through the course of their disease. So, that’s an unmet need that still requires attention and may alter the treatment plan for a given patient.

Katherine Banwell:                  

What about stem cell transplants?

Dr. Mascarenhas:       

So, we relegate stem cell plant transplants for those patients as mentioned before that are higher risk because we think that the potential benefit-to-risk ratio is in favor of transplant.

Transplant is really a modality that is the only modality that offers the potential for cure, but it’s also a modality that poses a significant risk of morbidity and mortality associated with it. So, it has to really be taken very seriously. It can’t be the kind of treatment you would think of as a last resort at the last minute. Once you see a transplanter, if they’re interested in that therapy and see it early on in the disease course, in my opinion, to start that dialog and then figure out when is the optimal time to employ a bone marrow transplant, which is not a surgical procedure. It’s often thought to be surgical. It’s not a transplant of an organ. It’s a transplant of hematopoietic cells. So, it’s really an infusion of stem cells that then end up in the person’s bone marrow, and they create a whole new hematopoietic system and immune system. And with that, you can have an immune system that then goes after the myelofibrosis stem cells.

That’s called graft-versus-leukemia effect. But with that included graft-versus-host disease, which is when the new graft, the new immune system doesn’t always recognize well the person’s own tissues, whether it’s the liver, or the lung, or the skin, and you can have immunologic reactions to that.

So, that’s a complex discussion. But, transplant, typically for patients less than 70 years of age who have high-risk myelofibrosis or even up to 75 if they have a good performance status and as we said don’t have a lot of comorbid issues with a goal of cure. So, if you have someone where their goal is to try to maximize their time out of the hospital and they’re not focused on longevity, their focused on quality of life, that may not be an appropriate patient for transplantation.

So, I think a very upfront, honest and a transparent discussion with the patient about what to expect with transplant, what are the pros and cons, what are the risks involved, and importantly does it match up with their expectations or their desires.

Myeloproliferative Neoplasms Defined: What Are ET, PV, and MF?

Myeloproliferative Neoplasms Defined: What Are ET, PV, and MF? from Patient Empowerment Network on Vimeo.

What are essential thrombocythemia (ET) , polycythemia vera (PV), and myelofibrosis (MF) exactly? Dr. Naveen Pemmaraju explains how each of these blood disorders manifests along with the symptoms observed in these MPN patients.

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju, here.

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Transcript:

Katherine Banwell:    

Can you help us understand the differences between ET, PV, and MF?

Dr. Pemmaraju:         

Yeah, this is very important because we toss these words around as if there’s some big definition that was given, and oftentimes, that never happens. So, let’s pause to do that. So, this goes back to the 1950s when William Damashek, who really postulated the modern MPDs at that time as they were known – myeloproliferative disorders – really thought that there were four diseases that were similar at some level and then presented differently. So, that’s polycythemia vera, essential thrombocytosis, myelofibrosis, and CML, chronic myeloid leukemia.

Then, as the modern era comes in, CML is divided off because of the Philadelphia chromosome, BCR-ABL, which is present in 100 percent of those patients.

So, now we know CML is its own thing. And now we have the big three, sort of non-Philadelphia chromosome MPNs, as they’re now known, because neoplasm – cancer – instead of disorder. Within the subtype, and this is important, the subtypes that you mentioned are the most common.

So, polycythemia vera – poly meaning many, cythemia, cells, vera is Latin for true.

This is the designation for the patient who has a higher than expected blood red cell mass or hematocrit. And it actually, interestingly, Katherine, most patients with P vera have an increase in all three of their blood lines, so the red cells, hemoglobin, hematocrit, platelets, and white count. Those patients with PV are especially at risk for both bleeding and clotting, transformation to myelofibrosis, and even transformation to acute leukemia in maybe 5 to 7 percent of patients.

So, the usual treatment there, Katherine, is to bring off the blood mass. That’s the phlebotomy.

And then in the patient who is above the age of 60 or has a prior blood clot, to give some form of chemotherapy, hydroxyurea (Hydrea), or interferon, for example.

Now, the second grouping is ET, essential thrombocytosis. Again, this word vera or essential, meaning not reactive, not benign, not from a regular cause like a surgery or a trauma or an inflammation. So, it means a cancerous cause, an autonomous cause, something that’s coming on its own.

Thrombocythemia or thrombocytosis, meaning too many platelets. So, usually, patients with ET have too many platelets as their predominant manifestation. But again, as with P vera, patients can get into problems with that. Very, very high platelets, usually a million-and-a-half or higher, can actually lead to bleeding. Not necessarily clotting, but extra bleeding. And then patients with any platelet levels, because the platelet level doesn’t exactly correlate, can have either bleeding or clotting. So, that’s usually the predominant factor. And again, the underlying problem with these MPNs is that they can transform to the other ones – PV, MF, even acute leukemia.

And then, finally, myelofibrosis, which we could spend the whole hour on just by itself, is the more advanced state out of these.

So, it can either arise out of the PV or ET or stand alone. And really here, this is an advanced bone marrow failure state with bone marrow scarring or fibrosis. And now, usually, most patients, their blood counts, rather than high are now low because the bone marrow is unable to produce enough cells. And then, therefore, the sequela of the disease – anemia, thrombocytopenia. So, low blood, low platelets.

Then you need transfusions. The liver and the spleen get larger because they remember how to make blood cells. People can have a wasting away appearance. And then here, more than the PV or ET, this is more of an acute disease for many where if you have intermediate to high stage, these patients can transform more readily to leukemia and have a decreased overall survival.

Shared Decision-Making: The Patient’s Role in Treatment Choices

Shared-Decision Making: The Patient’s Role in Treatment Choices from Patient Empowerment Network on Vimeo.

What is the role of the patient when it comes to treatment choices? Dr. Brady Stein details how he partners with patients in decision-making for their MPN care. 

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Transcript:

Katherine:                  

What do you feel is the patient’s role in the decision for therapy?

Dr. Stein:                   

I think it’s a really important role. I think historically – and, this is decades past; this era should be well over and behind us – this era of authoritative medicine is over.

You can’t just have a doctor walk in the room and say, “This is your treatment, this is what you should do, I’ll see you later.” It’s shared decision-making, and that can be troubling for some patients. But, the idea of shared decision-making is us explaining options informing the patient and making decisions together. That’s really the paradigm for modern contemporary medicine.

Some patients have a harder time with that. A lot of patients say, “Well, doc, this is too overwhelming for me. I just want you to decide for me.” And, we try not to do that. That’s a more uncomfortable type of visit for me when a patient is very deferential and says, “Whatever you say, I’ll do.” That’s not really what we want to hear. I want to know that you feel really informed, that you have a good understanding because each of these treatments – any treatment, any medication has its pros and cons.

There are no real magic bullets, and each upside has an equal downside, so you have to engage and open a dialogue, and what that means is that patients need to read and learn. That’s hard, but patients need to become proactive in their approach to their own illness, and all the patients who are listening now are doing that, trying to get more education about your relatively rare illness that’s going to give you a much better framework to help make decisions together.

Katherine:                  

Absolutely. If a patient isn’t feeling confident with their treatment plan or their care, do you recommend that they maybe consider a second opinion or seek a specialist?

Dr. Stein:                   

Of course, yeah. These are rare diseases, and patients often – I would say that in my clinic, a lot of the patients direct their own second opinions. Oftentimes, it’s coming from the patient more so than their doctor. I think the patient community is very active, the patients are networking, and they’re finding the right specialist to get to.

I think it should be really a team approach. It’s never – it’s usually not very convenient to go to a university unless you live really close, so you want to have someone close to home who can handle the routine, and then, someone who maybe is a little bit further away who can see you once a year, can help with the big decisions, can be part of the healthcare team. So, we generally recommend that you have someone near, and that maybe you have someone far who focuses only on MPNs as part of your team, and now, it’s a little different. Telemedicine is becoming a pretty ingrained part of medicine. It’s a little easier to have those visits with a physician who’s far away because of telemedicine.

Self-Advocacy: Advice for Being a Pro-Active MPN Patient

Self-Advocacy: Advice for Being a Pro-Active MPN Patient from Patient Empowerment Network on Vimeo.

How can myeloproliferative neoplasm (MPN) patients be more pro-active in their care? Dr. Brady Stein shares advice to help patients educate themselves about the disease, while finding the right balance of knowledge to prevent them from feeling overwhelmed. 

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Transcript:

Katherine:

Let’s talk about patient self-advocacy now, Dr. Stein. Patients can sometimes feel like they’re bothering their healthcare team with their comments and questions.

Why is it important for patients to speak up when it comes to symptoms and side effects?

Dr. Stein:                   

I smile a little bit because patients – I get a lot of patient emails by MyChart. That’s our medical record, and it’s a secure patient email, and a lot of patients will start their message by saying, “I’m sorry to bother you.”

And, I always say, “Why do you think that? It’s my job. Please don’t apologize for reaching out to me.” So, that’s kind of the first thing. Don’t feel like you’re bothering your doctor. There are certain things that we won’t know unless you tell us, and so, I think that’s pretty clear. When we’re in a patient room and there might be a husband and wife together, and whether it’s the husband is the patient or the wife is the patient, we might ask a question, and we might get, “No, everything is fine,” but all doctors kind of sneak over to the partner, and the partner may be saying – they’re making gestures to us. There may be nonverbal forms of communication to tell us there’s something much worse than what the patient is telling you.

So, again, “advocate” meaning you have to tell us what’s going on with you. If you’re worried about something, please don’t be stoic about it. These diseases are treated a lot based on your symptoms, and so, if you don’t tell uls about your symptoms, we won’t know.

And, in terms of advocacy, I think one of the things is that these are pretty rare diseases. In an academic center, no, this is our focus, but if you’re in a community practice where the doctor’s seeing 10-15 different things during the course of a day, it’s basically impossible to keep up with myelofibrosis, especially if you have one patient in your whole practice. I can’t do that for diseases that I see that I have only one patient. The medical literature can be overwhelming.

So, patients can quickly outpace their doctor in terms of their knowledge of these diseases, but I think it’s really important to read, to learn, and to think about the illness because you may find out things through your research that your doctor wouldn’t know are available. You may find a clinical trial, a new strategy, or a new test that they simply haven’t had the time to keep up with or learn about. So, that’s what advocacy is about. Reading is really important, but you have to find a balance. I want my patients reading, but you’ve got to find the right amount because there’s a certain amount of reading where the patients start to get overwhelmed.

All patients kind of get to this point. They take it in – like taking it in like a fire hydrant in the beginning of the disease, and it’s overwhelming, and then they start to find their balance. I think there’s a point where the reading becomes anxiety-provoking rather than ameliorating anxiety, and all patients just generally find their balance.

Is My MPN Treatment Working?

Is My MPN Treatment Working? from Patient Empowerment Network on Vimeo.

During myeloproliferative neoplasm (MPN) treatment, specific blood tests and diagnostic measurements help to gauge a patient’s treatment response. Dr. Brady Stein details the criteria he assesses in monitoring the efficacy of a therapy, including patient-reported outcomes.  

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Transcript:

Katherine:                  

Once a patient has started treatment, how do you know it’s working?

Dr. Stein:                   

That’s a good question because this is a very unique area. Yes, of course, in some respects, it’s straightforward with ET or PV. If we’re starting a medication to control a blood count in hopes of having lowered the thrombosis risk, you can look objectively at blood counts.

Okay, your hematocrit is at this goal? Yes, therapy’s working. You have not had a blood clot?

Yes, therapy’s working. So, there are some objective things. In myelofibrosis, there are some objective things like measuring the spleen and seeing it reduce. You can feel that with your hands, or you can do an ultrasound. So, there are some objective parameters of success. But, in this area, patient-reported outcomes are really important, and so, a measure of success is really just asking the patient, “Do you feel like your drug is working? Do you feel better?

It’s kind of a simple question, but it’s really important, and it’s what we ask in patients who are on certain therapies. “Do you feel like the net effect of your therapy is still positive? Do you feel like it’s helping?” Seems like a straightforward type of question, but I think the answer is extremely informative. When a patient says, “Yes, definitely, my medication is still helping me,” then I know that I don’t need to change it.

MPN Treatment Choices: Where Do Clinical Trials Fit In?

MPN Treatment Choices: Where Do Clinical Trials Fit In? from Patient Empowerment Network on Vimeo.

When considering MPN treatment approaches, clinical trials are a viable option for care. Dr. Brady Stein discusses clinical trials and factors to keep in mind when considering participation.

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Promising ET, PV & Myelofibrosis Therapies in Development 

What Are the Treatment Options for Myelofibrosis?


Transcript:

Dr. Stein:                   

Clinical trials are always a treatment – always an option for patients with myeloproliferative neoplasms because while we have some standards, we can definitely improve upon those standards for certain. So, clinical trials are always a therapeutic option. I think the one thing is that it may not – it’s not always the most convenient option, but it could be a really important option if available to you.

So, clinical trials basically offer something new or novel that would not otherwise be available to other patients. So, ruxolitinib (Jakafi) was approved around 2011, but the first clinical trials were in 2007, so that’s the example I give to a patient about the benefit of a clinical trial.The patient can get access to a drug that’s effective perhaps three to four years before it’s commercially available.

That’s really the biggest advantage, is you can get early access to something that could really help you. The downsides are that clinical trials are not usually as convenient as regular care, there are often more visits, and there are a lot of unknowns – unknowns about whether it will work. Some side effects are known and expected; there are others that are unknown. So, it’s a lot to think about, but I think it’s always important to consider, especially if your first-line therapy has not been effective, if it’s losing its touch, it’s a good thing to think about for a second line.

Katherine:                  

Are there emerging approaches for treating MPNs that patients should know about?

Dr. Stein:                   

Yeah, absolutely. I think the first question – I think patients are often worried that they have a really rare disease, and why would anyone do research in this area, and that’s – the research community is extremely engaged, the productivity is pretty impressive, and there’s a lot of clinical trials in the space, and I think what I try to explain is pharmaceutical companies aren’t just targeting the most common diseases.

They have interests in rare diseases, and findings in rare diseases can be extrapolated to other diseases that you might think are unrelated, but they can share features, so when you find something working in one space, it can have broad applicability. So, there’s an abundance of research in myeloproliferative neoplasms which are emerging?

In PV, I think there’s quite a possibility that there’ll be a drug approval in 2021, a novel type of interferon called ropeginterferon

That is a drug that’s approved abroad; it’s approved in Europe, and I believe it’s approved in Taiwan, and the FDA is looking at it now. So, it’s a possibility that there’ll be a future option for patients with polycythemia vera. So, yes, it’s research now, but it could be available, and so, that’s the drug that I’m starting to talk more and more about for patients with PV.

In myelofibrosis, you have two JAK inhibitors that are approved, ruxolitinib and fedratinib, you have two others in clinical testing, momelotinib and pacritinib, and then you have a whole other class of what we call non-JAK2 type of therapies targeting the vast array of pathway abnormalities in myelofibrosis.

So, there are a number of different clinical trial options, especially in myelofibrosis. I think that’s the disease area where there are the most clinical trials.

Understanding High-Risk vs Low-Risk Disease in ET, PV & MF

Understanding High-Risk vs Low-Risk Disease in PV, ET & MF from Patient Empowerment Network on Vimeo.

When looking at polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), how is risk determined? Dr. Brady Stein explains factors he examines when assessing risk to provide ideal care for each patient. 

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Transcript:

Dr. Stein:                  

For ET and PV, when we talk about high versus low risk, we’re talking about vascular complications, risk of having a blood clot. We’re not really talking about risk of transformation. We don’t have, I think, wonderful, widely used toolkits to predict those things. We know they can happen, but our treatment is still really based on clotting for ET and PV.

And, MF – each couple of years, the tools that are available to assess prognosis become more and more. So, in MF, we’re using the most comprehensive approach – of course, taking into account things like age and demographics, but also, looking at symptoms, looking at the depth and severity of blood count changes, looking at bone marrow features like the degree of scarring, looking at the rise in blast counts, and then, looking at chromosomes and novel genetic markers. So, we’re definitely the most comprehensive in myelofibrosis at assessing prognosis.

What Are Treatment Options for Essential Thrombocythemia (ET) & Polycythemia Vera (PV)?

What Are Treatment Options for Essential Thrombocythemia (ET) & Polycythemia Vera (PV)? from Patient Empowerment Network on Vimeo.

When considering treatment options for essential thrombocythemia (ET) and polycythemia vera (PV), where do experts begin? Dr. Brady Stein details treatment considerations and how he determines the best approaches for ET and PV patients. 

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Promising ET, PV & Myelofibrosis Therapies in Development 

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Transcript:

Katherine:                  

Let’s start with essential thrombocythemia, or ET.

Dr. Stein:                   

So, I think the first thing is taking an inventory of symptoms, seeing how symptomatic the patient might be. Again, there are some patients who are asymptomatic or have few symptoms, and they were told of a high platelet count during a routine visit, so some patients can be observed if they have few symptoms, and especially if they fall into a lower vascular risk category.

So, symptom assessment first. Second, looking at vascular risk, and there are four categories of risk in in ET in terms of predicting the likelihood of a future blood clotting event. There’s a very low, low, intermediate and high risk group, and that’s based on a patient’s age, whether they’ve had a blood clot before, and the type of mutation they have. JAK2 mutations increase the risk of clotting.

So, if a patient falls into a higher-risk group – say they’re older than 60 with a JAK2 mutation or they’ve had a prior blood clot – those are patients who are generally treated more aggressively with cytoreduction.

And then, the other thing is aspirin. We often see aspirin given to all patients with ET, but not all patients with ET necessarily need it. The role of aspirin is actually a little less clear in ET. For a very low-risk patient, there’s a potential for more harm than benefit, especially if the patient lacks a JAK2 mutation. So, the evidence base to support aspirin for all ET patients is just not there; it’s evolving.

Katherine:                  

What about polycythemia vera, or PV?

Dr. Stein:                   

So, there are a few standards. It’s different – the aspirin question in PV is generally answered by randomized data from 16 years ago in 2004. It’s been shown that aspirin reduces the risk of clotting in PV patients, so, generally, we give low-dose aspirin to all patients. And, hematocrit control is really important.

At least, a goal of 45 percent is mandated in PV. And then, there are patients who might fall into a higher-risk category – older than 60 or have had a prior blood clot – they need something more. And then, I’d also emphasize that there are lower-risk patients who may not be traditional candidates for cytoreduction, but they could have symptoms that really interfere with quality of life, and symptoms alone can be the trigger to add something more to the phlebotomy and aspirin program.

Katherine:                  

What about things like interferon?

Dr. Stein:                   

So, interferons have been used in MPNs for decades and decades. So, a longstanding history with interferons. The issue has been tolerability.

These days, there’s a class called pegylated interferon that’s longer acting, and I think there’s been a lot more use, at least in the last 10 years, still much more in an academic setting than a community practice.

But, interferons have a pretty established role in MPNs, especially polycythemia vera, for sure in ET, less so in myelofibrosis.

What Factors Guide Treatment Choices for ET, PV & MF?

What Factors Guide Treatment Choices for ET, PV & MF? from Patient Empowerment Network on Vimeo.

When making a myeloproliferative neoplasm (MPN) treatment decision, several factors come into play. Dr. Brady Stein explains what criteria he considers to determine the optimal approach for a patient’s unique situation and specific MPN.

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


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Transcript:

Katherine:              

Dr. Stein, I understand that therapy is different for each of the MPNs. What do you take into consideration to help guide the treatment choice?

Dr. Stein:                   

So, that’s a good question. It’s going to require maybe a little bit of a longer answer. It’s fairly nuanced. The treatment of ET and PV – right now, the goals are – the treatment is largely based on a patient’s vascular risk. That’s largely what influences the choice of therapy. And so if a patient has a perceived high risk for vascular complication in ET or PV, that’s when we’re going to be a little bit more aggressive – so, more aggressive than watchful waiting, more aggressive than using aspirin alone, more aggressive than using phlebotomy and aspirin alone in polycythemia vera.

So, if the patient has a higher vascular risk, in general, we’re going to need to do something more than what we consider to be the standard, and that’s where we enter into the question of cytoreductive therapy – therapies designed to lower blood counts apart from phlebotomy.

Maybe that’s going to change. I hope it will change. Right now, the therapy for ET and PV is generally reactive. We either predict high risk and react, or if a patient is lower risk, if something changes – God forbid there’s a blood clotting event – then we may react to it.

So, ET and PV treatment are generally more reactive. In myelofibrosis, certainly, there are patients who can have lower risk and minimal systems, and there are some patients who can be observed with watchful waiting for sure, but more patients are symptomatic, more patients are going to need therapy in myelofibrosis, and there’s sort of two big categories of therapy.

One is the risk-adapted, deciding if the patient is eligible and should consider stem cell transplant versus thinking only about medical therapy in a patient that may be transplant-ineligible.

And, the medical therapy is based on the worst symptoms for the patient. Is the symptom that’s the worst the spleen enlargement? Is it excessive fatigue? Is it weight loss, or inflammation, or fevers? If it’s that category of symptoms, we have a set of therapies. If it’s really the anemia that is the most problematic issue, then we follow a paradigm to treat anemia.

Katherine:                  

What about considerations like the patient’s health, age, genetic markers, things like that?

Dr. Stein:                   

So, of course. The comorbid illnesses can influence therapy choices, so if a patient is older and has other medical conditions, they’re not going to be treated as aggressively.

So, in myelofibrosis, if a patient is older, with other medical illnesses, then it may be inappropriate to consider something like stem cell transplant, for sure. So, age and health comorbidities are highly influential. In terms of genetic features, if you’re asking about things like the type of mutation that a patient has, right now, we’re – in terms of vascular risk, for ET, the type of mutation matters for blood clotting risk, so if patients have different mutations, it could be treated differently. In other subtypes, like PV or myelofibrosis, in general, there’s – the mutation can be prognostic, but it may not be – it may not lead to a precise and distinct therapy just yet.

How Do Test Results Inform MPN Prognosis & Treatment?

How Do Test Results Inform MPN Prognosis & Treatment? from Patient Empowerment Network on Vimeo.

Dr. Brady Stein explains the diagnostic tests and genetic mutations that are assessed to determine prognosis and what MPN treatment may work best.

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 


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Transcript:

Katherine:                  

Once a patient is diagnosed with MPN, what sort of testing should take place?

Dr. Stein:                   

So, the test that’s going to lead to suspicion is going to be a blood count, and that’s probably going to be done in the primary care doctor’s office, so that’s going to be the first suspicious test, and in general, there’s going to be some abnormality. Myeloproliferative diseases are characterized in general by an overproduction of blood cells, so it’s going to be a higher white count, it’s going to be a high hemoglobin or hematocrit, or a high platelet count, or a combination of the three that’s generally going to lead to suspicion.

Some patients may have pretty unremarkable blood counts and may present with a blood clot in an unusual location that could ultimately lead to the hematology referral. Some patients might have pretty unremarkable blood counts, but they might have palpation of their spleen, enlargement of their spleen in a physical examination. So, they’re generally the ways that patients are getting to the hematologist.

Katherine:                  

And, what about bone marrow biopsy?

Dr. Stein:                   

So, a bone marrow biopsy is a diagnostic test, and it’s generally recommended for all patients who have a myeloproliferative neoplasm either confirmed or suspected.

It’s advised in WHO criteria – World Health Organization criteria. PV can be made without a bone marrow biopsy – a diagnosis of PV – because it’s the most unique of the MPN subtypes. It’s the one that presents with a high hemoglobin.

So, that diagnosis can be straightforward at times for a hematologist when the setting is right, when there’s a high hemoglobin – or, high enough hemoglobin, I should say, a JAK2 mutation, which all patients with PV have that, or a subnormal erythropoietin level.

Oftentimes, we can make that diagnosis without a bone marrow, and the bone marrow becomes more prognostic. ET, a bone marrow is necessary for diagnosis, and myelofibrosis, you can’t make a diagnosis without it.

Katherine:                  

What do the results of these tests tell us about prognosis and treatment choices?

Dr. Stein:                   

That’s a good question. The bone marrow can be diagnostic in the setting of ET and myelofibrosis. In the setting of polycythemia vera, it can be more prognostic. In general, when a bone marrow is done, 1). To confirm diagnosis, 2). To assess prognosis, what we’re looking for as prognostic features are generally the degree of fibrosis or scarring.

So, each of the MPNs can have that. Of course, MF is characterized by the most pronounced scarring. It can happen to a more subtle degree in ET and PV. That’s going to be prognostic in the setting of ET or PV. The pathologist will alert us about immature cells called blasts.

We basically never see them at diagnosis in patients with ET or PV. We can see them rise in patients with myelofibrosis at diagnosis or through the course of follow-up. So, that’s prognostic.

All bone marrows generally have a chromosome analysis that’s called cytogenetics, and so, if there’s an abnormality, that can help place the patient’s prognosis into different risk categories.

And then, nowadays, more so in myelofibrosis than any of the others, there are extended panels done. These are called NGS, or next-generation sequencing, kind of looking at mutations in a greater degree of detail.

So, not just what we call main mutations – JAK2, calreticulin, or MPL. These are looking at additional mutations that basically hold prognostic significance.

These are pretty well defined, and I think more important in MF compared to the other subtypes.

Katherine:                  

Would you explain the driver mutations in MPNs? What are they, and how they – or, what they mean for patients?

Dr. Stein:                   

So, there’s three of what we call driver mutations, and the most common is JAK2V617F, the next most common is calreticulin, and the least common or most rare is a mutation of MPL, the thrombopoietin receptor. So, the driver gene mutations are the three that we assess to help with diagnosis, and the prevalence varies. In ET, about 60 percent have JAK2, 25 percent have calreticulin, 5 to 10 percent have MPL.

In PV, 99 percent have some type of JAK2 mutation, and in MF, the situation is a lot like ET – 60 percent JAK2, 25 percent calreticulin, about 5 to 10 percent MPL. So, the driver mutations – we think of those as the genetic abnormalities that really drive the disease. They’re the main ones we can test for in a diagnostic setting.

I refer to them as the – to a patient, what I’m describing is you have a car, and the driver mutation is the one that’s sort of driving the car, and it’s doing it somewhat recklessly. It’s in the front seat, driving. And, along the way, the driver can pick up hitchhikers, which we should never do. I refer to those other mutations that are found by NGS as hitchhiker mutations that sit in the back seat, cause trouble, and really shouldn’t be there. They’re not the driver, they’re not fully responsible for the disease, but they can make it a bit worse.

How Often Should You See Your MPN Doctor?

How Often Should You See Your MPN Doctor? from Patient Empowerment Network on Vimeo.

Dr. Laura Michaelis discusses how frequently patients with essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) should visit their doctor. 

Dr. Laura Michaelis is hematologist specializing in myeloproliferative neoplasms (MPNs) at Froedtert & the Medical College of Wisconsin, where she also serves as Associate Professor of Medicine. Learn more about Dr. Michaelis here.


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Transcript:

Dr. Michaelis:             

So, the regular follow-up for myeloproliferative neoplasms, whether that is somebody with ET, PV, or myelofibrosis, is incredibly variable. It depends on the risk stratification. It depends on how frequently you’re needing intervention.

For example, somebody with low-risk polycythemia vera whose hematocrit is elevated and gets a phlebotomy – that person I follow relatively frequently.

Maybe every month or so until I know for sure that the phlebotomy frequency, the number of times we are removing blood, and the frequency, the rate at which that happens, is adequate to ensure that that person is not spending too much time with a hematocrit of over 45 percent.

We know that because randomized trials have shown that a hematocrit over 45 percent leads to an increased risk for bad clinical outcomes.

So, early on in that person’s trajectory, I might check their blood counts more often. Once I know that they are stable and can go longer periods of time, we can relax that out. And that may happen, for example, when they become iron deficient, and the need for phlebotomies decreases.

In somebody with essential thrombocythemia that’s well controlled, again, one might do blood counts every three months or maybe, if things are very stable, every six months.

This is something that I usually make sure that I’m following the national guidelines on and that I adjust from a patient standpoint. If somebody is seeing their PCP in three months and getting blood counts, and things have been stable, then there’s no reason to see more frequently.

Now, when do I see people more frequently? For example, if they’ve started a new treatment, and we want to make sure that their kidneys and liver are doing okay. If I’ve noticed a change in one of their organ functions on the basis of something and do a little tweaking of their medicines, then I might see them more frequently.

So, again, there’s no set-in stone. This is part of the art of medicine, and you wanna talk with your doctor about what you should expect and who’s gonna be following up on the tests that are drawn.

MPN Treatment Decisions: Which Path is Best for You?

MPN Treatment Decisions: Which Path is Best for You? from Patient Empowerment Network on Vimeo.

Dr. Ruben Mesa provides an overview of available treatments and reviews important factors to consider when choosing a therapy for essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis (MF).

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

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Transcript:

Dr. Ruben Mesa:

The treatment landscape for myeloproliferative neoplasms is changing very rapidly. And in a good way, it’s increasingly having many more options for patients with Myeloproliferative Neoplasms. But I would separate it, really, into two groups. First, there are those individuals with essential thrombocythemia and polycythemia vera.

These individuals, we have newer therapies, such as interferons, we have, potentially, use of JAK inhibitors, we have some experimental therapies, as well as prior therapies we’ve used and become accustomed to, including hydroxyurea, phlebotomy, and aspirin.

But we’re learning much more about how to use these therapies; how to combine them; what constitutes success with these therapies; what should constitute a change in terms of therapy.

And there are new therapies being developed in the future that will impact this group of individuals with earlier MPNs: ET and PV.

For patients with myelofibrosis, the treatment is evolving. Patients with Myelofibrosis are affected in different ways. It is, in some ways, a more problematic disease.

There is evolution of our most impactful therapy, of stem cell transplantation. We have a better sense of in which patients we should consider that treatment, and how that can be applied in the safest way. We also have more medical treatments. We just saw in 2019 the approval of Fedratinib as the second specific JAK inhibitor approved for patients with myelofibrosis.

We, additionally, now have, truly dozens of clinical trials of new therapies in development that are in clinical trials right now that might be helpful for patients with myelofibrosis who have either had Ruxolitinib, or have a suboptimal response to Ruxolitinib, or sometimes even newly diagnosed patients. But I would say the future is very bright.

So, it is key with a treatment to first understand what is the treatment, what is the dose, and what is the goal? Each of the treatments have different goals. Some of the goals are to decrease the likelihood of blood clots or bleeding.

And frequently, we assess whether we’re protecting against the blood clots or bleeding by bringing down elevated counts. Is the plate account high, and we’re trying to bring it into the normal range? Is the hematocrit high, and we’re trying to bring that to under 45%? Is the white blood cell count high? Have we lowered each of those? First, it’s around controlling blood counts if that is the goal, as well as trying to decrease at risk of blood clots or bleeding.

 Second, if patients have symptoms associated with their MPN, sometimes itching, sometimes symptoms associated with high courts, sometimes enlargement of the spleen, or symptoms associated with the spleen, have we reduced or nullified those symptoms? Have we shrunk the spleen if the spleen was enlarged?

And then, finally, we assess our goal by trying to be sure that patients are not progressing or getting worse on the disease. So, depending upon the treatment, we first asses what is our goal? Is it to improve counts? Is it to improve symptoms? Is it to shrink the spleen? And have we accomplished one, two, or all three of those goals? Or was only one those our goals to begin with?