Living Well with MPNs – The Power of Diet & Exercise

The Power of Diet & Exercise: Advice From MPN Experts

Living Well With MPNs: The Power of Diet & Exercise from Patient Empowerment Network on Vimeo.

The expert panel featured renowned MPN specialist and researcher Dr. Ruben Mesa and was joined by other experienced clinicians and patients on the broadcast, to share knowledge and advice about the benefits of a healthy lifestyle when dealing with myeloproliferative neoplasms (MPNs).


Transcript:

Andrew Schorr:

And hello, wherever you may be. Welcome to this Patient Empowerment Network program. I’m Andrew Schorr from Patient Power. We’re going to discuss the power of diet and exercise, and get advice from MPN experts. We want to thank Insight Corporation for their support. We’re gonna cover the country – the U.S. country – today with our experts. I have my own experience with an MPN, myelofibrosis, diagnosed in 2011, and I’m an avid runner, and I like to go to the gym, and I certainly like to have my weight be just right. Some of this has been a challenge along the way, and we’re gonna get advice from the experts on that. We’re also gonna meet a patient from New Jersey, and we’re gonna meet a noted expert from San Antonio, and a dietitian who’s an expert in oncology diet, and she’s in North Carolina.

So, let’s get started. And remember, you can send your questions to MPN@patientpower.info. And if you have some favorite recipe or some exercise tip, send that too. All right, let’s go first to Westfield, New Jersey, about 19 miles from New York City, meeting someone who grew up in Brooklyn but now lives with her family in suburban New Jersey, and that’s Julia Olff. Julia, welcome to the program.

Julia Olff:

Hi, thank you very much.

Andrew Schorr:

Thank you, Julia. Now, Julia, you and I have met a couple of times. We did a Town Hall event in New York City near Grand Central Station, and you were there. And then a few weeks ago, we were all at Cornell Weill, and across from where you used to work for five years at Memorial Sloan Kettering. So, as I understand it, nine years ago, you were diagnosed with ET, and then a year later, it became what I have too, myelofibrosis. How did it start?

Julia Olff:

It really was diagnosed incidentally through a physical – annual physical exam and routine blood work.

I think in retrospect, I had symptoms. Probably like other folks, I had thalamic migraines over the years and some blood abnormalities, but it was really a physical exam. And I was not symptomatic that I was aware of at that time.

Andrew Schorr:

Okay. And it didn’t worry you, at that point.

Julia Olff:

I mean, I know we’ll talk more about it. I worked in health education. I worked on patient education materials at the time. When I was told I had ET, I was sort of thrown because I was one of those people that were always healthy, always focused on health. And it concerned me, but I was not yet worried.

Andrew Schorr:

Okay, so here comes myelofibrosis.

Julia Olff:

Right. That worried me. So, that also was diagnosed at that point then through bone marrow biopsy, and they were able to determine some initial mutations related to myelofibrosis.

And I saw a local oncologist, who was now more serious about this as the more serious form of the illness, and looking on the Internet. And now this is actually about 2008. You know what kind of information was available at the time. It was pretty dire. So, that kick started my getting more serious about it.

Andrew Schorr:

Okay. Now, you’ve had some hospitalizations, too. So, it’s been up and down, right?

Julia Olff:

Yeah, I think it’s a real ebb and flow. I feel, in a lot of ways, fortunate that it’s nine years out, and I have not had some of the hallmark symptoms that others have. But I have had these strange, sort of out of nowhere; I can feel fairly good, barring fatigue and some pain. And then out of the blue, I had a TIA. I’ve had a few hospitalizations for colitis. And those set you back, you know?

They take a good six to eight weeks to recover. And if you saw me in August, you would see the really lethargic, slow-moving me.

Andrew Schorr:

So, what’s your exercise routine?

Julia Olff:

Well, I know we were talking earlier. I had two dogs, most recently one, and he just passed away. That has been my exercise routine. So, I don’t feel energetic enough to do things like biking, even though I have a lovely bicycle. But I do try to walk every day. And right now, I’m feeling well enough that I push myself to walk a little longer. And I think as it gets darker in the year – I’m on the East Coast. As it gets colder, I do really have to push myself. But I wholeheartedly advocate for having a pet, because you need to get out, and that really helps a lot. So, walking is key for me.

Andrew Schorr:

And diet, I know. So, you’ve got a high school kid at home and a college kid who’s coming back. And you’ve had five children in a blended family, I know. So, it can be a busy place. What do you eat, and what do you eat consciously that you feel helps you as you’re living with an MPN?

Julia Olff:

Well, I think the thing that’s helped me the most is actually following Weight Watchers. And I know we were talking earlier that being on Ruxolitinib or Jakafi has added pounds. And it has. And that sort of prompted me. I finally got fed up with myself, and I joined Weight Watchers. And I think the most important aspect of Weight Watchers is, one, portion control. And then the other part is eating fresh food. So, that changed or really pumped up my diet. So, one, I started to receive organic groceries delivered to the house, which also helps a lot when you’re feeling fatigued. So, I try to eat as many fruits and vegetables at every meal. And I feel like that’s helping me.

Andrew Schorr:

Okay. All right. We’re gonna get more from you along the way. And I want you to chime in with questions. Let’s meet one of the best-known experts as a physician devoted to treating MPNs, and that’s Dr. Ruben Mesa. He recently moved from where he was with Mayo Clinic in Arizona, and now – you’ve got a long title, Ruben. I’ve got to give it. It’s Director of Mays Family Foundation, Distinguished University Presidential Chair Professor of Medicine at the UT Health San Antonio Cancer Center. I’m so glad I got it right. Ruben Mesa, welcome to our program. It’s great to see you again.

Dr. Ruben Mesa:

Hey, it’s always a pleasure to be on these Patient Power events.

Andrew Schorr:

Thank you so, much. And Patient Empowerment Network program. Thank you so much, Ruben. So, Ruben, we’re gonna come back to you and have you really put diet and exercise in perspective.

And I know you’ve seen thousands of patients. And I’m sure patients have shared with you every diet, every kind of exercise. You’ll have stories to tell, won’t you?

Dr. Ruben Mesa:

Absolutely.

Andrew Schorr:

Okay. All right. Let’s skip over to Winston-Salem, North Carolina, and meet someone who’s been on other programs we’ve produced. And that’s Julie Lanford. Julie is a registered dietitian, nutritionist. But beyond that is at Cancer Services, a nonprofit in North Carolina, Julie is an oncology dietitian. Julie, welcome to the program.

Julie Lanford:

Thank you so much.

Andrew Schorr:

Let’s get started. So, first of all, Ruben, we’ve heard you talk a lot about the differences in MPNs. And so, really, there’s not a one size fits all, even really the diet and exercise, Ruben, is there?

Dr. Ruben Mesa:

There truly is not. I mean, certainly, with MPNs, we really have to think about diseases that people live with. They live with, for long periods of time, many even the rest of their lives – with their MPN. So, again, I try to frame it for folks. For many, it’s really about managing a chronic condition. And being a chronic condition, the things that we do in terms of our lifestyle are very important, both in terms of what we eat, how active we are, how well we sleep. There are many key parts that are related, without question.

Andrew Schorr:

Okay. I gotta ask one question off the top. Julie referred to it, and I wonder about it, too. So, I’ve been taking Ruxolitinib for five years. Julia, for four, I think you said, Julia.

Julie Lanford:

Yes.

Andrew Schorr:

And so, what I wonder about, Ruben, is there anything about that medicine that some of us take, some people for PD as well, that lends to weight gain, scientifically?

Dr. Ruben Mesa:

It’s difficult to know. Clearly, people gain weight, at least on average, to some degree, with taking Ruxolitinib. Now, part of that reason for weight gain is that an MPN causes weight loss overall. And MPNs in general burn more calories than if you don’t have an MPN. The activity in the bone marrow, all those cells being produced, and turning over that burns more calories than it does otherwise. So, part of the weight gain may be turning off that extra calorie burn that the MPN caused. So, part may be, again, you’ve kind of adjusted your diet, etc. In the past, you were able to get away with eating more. And then if the disease is quieter, you gain some weight. Now, I’d say even though that’s part of it, it does seem that people do gain a little bit more weight than even that with the Ruxolitinib.

And it may well have to do in part with some of the secondary effects of the Ruxolitinib. Ruxolitinib inhibits JAK2. That’s one of the key reasons it was tested in MPNs. And with that, helps to shrink the spleen, helps people feel better. Maybe help even avoid progression of the disease or decrease that likelihood of progression. But it has an impact on a whole bunch of different proteins that circulate in the blood that we call cytokines. Cytokines can be involved with inflammation, but they may be involved with other parts that kind of control how things are working in the body. And it may be blocking of some of those cytokines that may account for a little bit of that change in weight.

Andrew Schorr:

Hm. Okay. And related to the other medicines that we take, some people take interferon, some people take hydroxurea, depending upon where they are – maybe just aspirin, depending on where they are with an MPN.

Are there other common things that affect weight related to any of those medicines?

Dr. Ruben Mesa:

It’s a good question. In general, the weight gain has been much more specific to the JAK inhibitors. I can’t say it’s specific to Ruxolitinib, but it really is an effect with JAK inhibitors. Most of those other medicines, hydroxyurea or interferon, don’t have a big impact on weight in terms of gain. Whether that’s in people with myelofibrosis who have lost weight related to the disease, even if they’re on hydroxyurea, they don’t tend to gain some of that weight back. So, myelofibrosis, we do view that some of the weight gain might be beneficial, because some of that weight loss in myelofibrosis is not just fat. It can be muscle. But again, there may be some part that is an extra effect of weight gain from the impact of the drug.

Andrew Schorr:

Okay. Julie Lanford, so let’s talk about managing weight. So, I’ve been – and Julia mentioned it earlier. I mean, I’ve been – no more cookies for me. And I love chocolate chip cookies. So, I’ve had to make changes. How do you coach people through changes, if, let’s say, maybe there’s something related to inhibiting whatever in their body, we have to make changes.

Julie Lanford:

Yeah. So, I will say, I don’t actually keep a scale in my office because I think that a lot of times, you can get kind of distracted on the number. You do know, though – I find many patients know by how their clothes fit, by how they feel. And I think what’s important also is what type of weight is it? Is it muscle weight? Muscle weight’s good, right? Or is it more excess fat? And so, I think balancing those things and really keying in on what are the behaviors that we want you to have, as opposed to what the number on the scale, per se.

But are you able to be physically active that helps maintain muscle mass, and are you choosing those really healthy foods for you? Like Julia was saying, lots of fruits and vegetables, which are really important, not just for weight maintenance, but for overall feeling well and helping to support your immune system, and just overall good health.

Andrew Schorr:

Hm. And so, with this belly that I’ve developed, I had to make a change. I used to have a toasted bagel every morning, Julie. I’m not doing that now. And I put chocolate syrup in this latte machine thing. No more of that. I mean, these are things I’ve had to give up. But I’m having jelly with no sugar in it on a whole wheat waffle, and I’m eating a banana. Am I doing okay doing that?

Julie Lanford:

Yeah. I think – and sometimes, we discount the little things. But I think the little things are sometimes – they make the biggest difference. Because if they are things that you do on a daily basis, and you make a change, it’s gonna have a big impact. Now, you’re talking about your cookies. If you just had a cookie or two once a week, it’s not that big of a deal. But if you were having a cookie after lunch every single day –

Andrew Schorr:

I was.

Julie Lanford:

Then changing that habit – okay. Well then, approved. You can cut back on that. It’s a good choice, right? We don’t want you to completely eliminate it. But really keying in on what are you regular habits, I think, is the most important place to start. And I always encourage people to really pay attention to what they have on their plate, what are the ratios of food that’s on their plate, so that they are getting enough of the nourishing nutrients. And sometimes that helps to, when you make those changes away from the less healthy things; you don’t notice it as much when you’re focused on including more of the healthy things.

Andrew Schorr:

Well, I just want to make one comment. We lived in Europe, some people know, for three years. And the first thing that hit us when we came back to the U.S. is the much bigger portions. And there you are, Ruben – you’re in Texas. Texas-sized food. Or even in California. My mother used to say, “Clean everything on your plate,” but I’m rethinking that, so. Julia Olff, I want to go back to you. So, related to – so, what kind of fruit are you eating? What change have you made? You said fruits and vegetables and organic stuff, too.

Julia Olff:

Well, I have a question in relationship to the conversation that we just had that I wanted to come back to. But I think because of Weight Watchers, my awareness of both weight and nutritional value of food has just heightened. So, one of my big questions in relationship to myelofibrosis that I have tried to adjust but haven’t eliminated – I’m a foodie. I live for food. To me, life – I’m not sure I want another year of life if I can’t have a cookie.

And so, I’ve tried to reduce the amount of fat I take in. And I think I have a lot of questions about salt, sugar, and fat as it relates to having a myeloproliferative neoplasm, being at risk for bleeding, blood clots, etc. But I would say, like you, I have a more structured – my meals are more intentional. So, like you, I have a bowl of fruit for breakfast every single day, and then I try to have something that’s – if I’m going to have a carbohydrate, I try to make it a better carbohydrate. I make use of hardboiled eggs a lot, so I get a little protein, and try to have greens at dinner every night. And a few of them – as a matter of fact, my husband said to me the other week, “Sure, make me a plate.” He was on his way home.

And he came home, and he looked at his plate, and he said, “That’s such a big plate of food.” I said, “Look at the balance. Half of it is vegetables. It’s really not so – it’s not like I’ve stuffed you.” “Oh, okay.”

Andrew Schorr:

So, Ruben, are there some things that in the clinic, you warn people to stay away from? Do you have some general advice, or certain foods, or if somebody’s worried about sludgy blood, where they’re at risk of a stroke, that certain kind of foods or salts or whatever that you warn people about?

Dr. Ruben Mesa:

Well, when it comes to diet and MPNs, I mean, I think there are several levels. And one, let’s say, the general U.S. diet. People kind of eat whatever they want. And that’s probably not healthy for anyone. High in salt, high in fat. It’s a risk for us all in terms of cardiovascular disease, etc. And when you have an MPN, all of those standard risks with cholesterol and sugar and high blood pressure, they’re even a greater concern with MPNS, without question.

But that’s kind of diet one. Diet two, and we can definitely dig into this, regards just trying to eat a healthier diet. And that has different values, whether it’s straight weight loss, or a just a general healthier diet, I think, of which there’s a lot of discussion as to a lot of variations within there. But even just the effort of trying to eat healthier, both in terms of quantity and what you’re eating, has an impact. And there’s finally, the third group, really kind of subspecialized diets, of which I think there is great discussion, but I don’t think that there’s near conformity of should it be gluten-free? Should it be high in protein? Should it be low in protein? Should it be paleo? Should it be this? Should it be that? I think that is more mixed.

But I think for MPN patients, the most particular thing is at least trying to not be in that first group of just kind of the general U.S. just kind of eat food as it comes, fried, salted, really without regard to diet. So, even if MPN patients just followed the diet that we’re all supposed to be following, they probably are in dramatically better shape than just if they’re eating just a general U.S. diet.

Andrew Schorr:

Okay. I want to ask you a couple of things about exercise. So, some people with high blood counts worry that they are certainly at risk of stroke. Should that, during that time, limit the amount of exercise they do for fear that the stuff pumping ever faster through their body is gonna end up with a big blood clot somewhere?

Dr. Ruben Mesa:

Sure. No, that’s a very good question. One, overall, exercise for MPN patients is a very good thing. But clearly, it should be done with kind of the awareness of their physicians. And that in periods of time where the disease is not stable – the counts are too high and uncontrolled, there’s just been an event such as a blood clot or bleeding, clearly there might be times where exercise is not appropriate until things are more balanced and in control. But I’d say once things are balanced and in control, and as long as your healthcare team is aware, appropriate exercise is helpful and important. I think, like any approach to healthy exercise, it’s about gradually working yourself into a specific exercise program. With an MPN, it’s probably not good to do what happens on January 2nd every year, where everyone has a New Years resolution.

And they go from, okay, I’m not exercising at all, to I’m gonna go to Lifetime, and I’m gonna exercise an hour and a half on January 2nd, and absolutely dehydrate myself and exhaust myself, so by January 4th, I’ve quit because I pulled a muscle and I feel terrible. So, it’s clearly about kind of working yourself up to an appropriate level of exercise, in combination with what your doctor feels is appropriate and healthy for you, both in terms of your overall health, but also in terms of where you stand with your MPN.

Andrew Schorr:

Mm-hmm. So, Julie, you’re nodding your head. How have you carried on with exercise? Walking the dog, but what other kinds of things?

Julie Lanford:

Well, I wanted to add, as I’m listening to Dr. Mesa, that pacing is so important. Because I find it catches up with me. I could sleep, on average night, nine, ten hours, and I have to push myself out of bed in the morning.

 So, yesterday, I had an evening meeting. I took a long walk. And in the moment, I’m okay, but by the evening, I start to feel achy. I need to put my feet up. The bone pain in my hips starts to kick in. So, there’s that balance of trying to get out as much as possible. So, for me, it’s taking advantage of the sun outside my window. And I’m already thinking, as soon as we’re done with this call, I’m gonna take another short walk. But it’s also trying to balance it, because too much activity when you have constant fatigue just catches up with you. And I find I end up having those acute bouts of illness when I’ve done too much for a sustained – like for a couple of months.

Dr. Ruben Mesa:

If I might just add one additional thing. That pacing thing, I think, is so important.

As I told you, I’ve had many patients over the years who are very Type A. Some of them will be on this webinar as we speak.

Julie Lanford:

Yup.

Dr. Ruben Mesa:

And they’re very hard on themselves because they remember, well, before my MPN, I was able to exercise this amount, and beat themselves up because they just don’t have the same stamina that they did before. And it’s okay. It’s okay to realize that the new normal does not necessarily mean that you have 100 percent of the capacity that you had before in terms of your exercise capability, and that even though it’s modified, or less, or adjusted accordingly, it’s still great that you’re doing it.

Andrew Schorr:

Right. I have a story about that I’ll just share. So, as we do this program, it’s just after Thanksgiving. So, there was a Turkey Trot, as there were in many places around the country, in Balboa Park on the north side of LA.

My son, Ari, won it. He’s a really fast marathoner. But Esther and I ran it, and Esther and I were running together slowly. And I found I was huffing and puffing, and I’ve run eight marathons, many years ago. And I just said, “You know, I just want to finish.” And Esther went ahead. She did really well. Congratulations, Esther. And then my son who ran the race came back and ran the last mile with me. So, it was a 5k, so a little over three miles. I felt great that I did it. I felt disappointed that I couldn’t do what I used to. But I did it. And I think it’s exactly what you’re saying, Ruben. So, Julie Lanford, are there certain foods or things we can do that will give us more energy, and some things that are just a waste?

Julie Lanford:

So, I would say that we do want to focus on foods. There’s no supplements. Unless you’re deficient in a nutrient, there’s no reason to take pill forms of nutrition.

So, we do want to focus on the foods. And there are certain patterns of eating that we know are particular healthy, and certain patterns that are not so healthy. We’ve talked about the typical American kind of eats a pattern that’s not so healthy. And when it comes to fatigue, I would say similar types of foods as we want for an overall healthy diet. But I think it’s really key that people not wait too long to eat, so that they’re – just like your pacing, everything else in your day, you want to make sure that you are eating regularly throughout the day so that you never get real low on energy in terms of nutrition.

And also, really making sure that you have a good balance of foods at your mealtimes and at your snack times. So, you want to make sure you have a healthy carbohydrate, because that’s what can really give your brain and your muscles energy. You want to make sure you have a good balance of proteins. They can come from plant proteins or animal proteins. But make sure that your meals and snacks have an adequate amount of protein.

And then, of course, some fruits and vegetables and other things. But really getting that balance, and also not going too long between when you eat, so that you can consistently give your body that energy that it needs. Even if it’s smaller amounts at a time, it’s spread out throughout the day regularly.

Andrew Schorr:

So, when I went to summer camp as a kid, they had us eat candy bars if we were low on energy. And we’re talking about carbohydrates. So, kick off a couple of specifics that you would recommend that we should – snacks, for instance.

Julie Lanford:

Yeah. So, probably wouldn’t recommend a candy bar, per se, on a regular basis. But things like peanut butter crackers, if you can buy just good old whole grain crackers and peanut butter and put them on there, that can be easy. Even a peanut butter sandwich is really simple. Peanut butter and banana. People around here eat that. I think it’s delicious. Soups can be easy things that are kept either in the fridge – that’s easy to heat up.

Because that’s the other thing with fatigue. You don’t feel like cooking, so you want to make sure that you have sort of meal-sized portions in your fridge ready to eat. That’s what friends and family can kind of do for you. So, even just small meals. If it’s spaghetti, if it’s a piece of pizza that you put lots of vegetables on. I think fruit is great as a source of healthy carbohydrates. If you had fruit and a cheese stick, or even if you made yourself some sort of healthy smoothie, just something that’s going to give you that balance of nutrients.

Andrew Schorr:

Yeah. You mentioned something, and Julie, I don’t know if you do it. We had started to – I love leftovers. And so, we’ve been trying to make healthy stuff, put it in the fridge where I can grab for lunch. Or this morning, Esther made a big thing of steel-cut oatmeal. And so, now I can have that as part of my breakfast. So, Julie, is that – are we on the right track?

Julie Lanford:

Yeah, that’s great. And something that’s really popular right now is overnight oats. So, you can soak your oats in milk or whatever or whatever you want to use for a liquid, and it’s in a jar, or it’s in a container in the fridge all night, so it gets soft, so it cooks really quickly in the morning in the microwave. So, yeah, I think that’s a great way – there are lots of grains you could use for breakfast cereals, too. Barley is another grain. Quinoa. And essentially, you cook it the same as you would oatmeal. Flavor it the same way, and it just gives it variety if you’re looking for something different.

Andrew Schorr:

Julia, how’s that sound to you?

Julia Olff:

I’m not a big hot cereal fan, so I have two breakfasts that I go back and forth from. One is – I love Cheerios, and I just read how much sugar there was in Honeynut Cheerios, so I’m mixing plain Cheerios now with Honeynut Cheerios, and then I add a lot of fruit to it. Or I do a whole grain muffin with half a hardboiled egg, which makes me miss my dog, because I always gave him the other half of the egg.

Andrew Schorr:

I have a blood count question for you with myelofibrosis. How are your platelets?

Julia Olff:

For me?

Andrew Schorr:

Yeah.

Julia Olff:

They are – since I started Jakafi, they’ve controlled like they have never, ever been, or not in a decade. So, they’re probably between 250 and 300, I would say.

Andrew Schorr:

Oh boy. Okay.

Julia Olff:

Yeah. I’ve got platelets to spare.

Andrew Schorr:

Well, I would take some. So – and Ruben knows this about me. So, my platelets have traditionally been low, and they got as low as a few months ago, 40,000. And now I’ve been doing through treatment, actually, for this other condition I’ve had, chronic lymphocytic leukemia, and they were up to about 100. Ruben, one of the things I was told by my doctors was don’t do contact sports, because my spleen was getting larger, and also, I had low platelets.

So, what about the kind of exercise you do if your platelets are lower? What’s your thought about that?

Dr. Ruben Mesa:

Well, I would say that, barring extremely low platelets, i.e., under 15,000, most routine forms of exercise that are cardiovascular, that are elliptical machines, that are weight-lifting, others sorts of things – all of those sorts of things are fine. I think the sports that one would probably avoid with either of those situations is truly kind of contact teams sports – rugby, football, etc., where there’s very significant contact. Down here in Texas, I certainly have seen people riding the mechanical bull. I’m not sure that’s a good idea for anybody, but those sorts of extreme things. There is a bit of a misperception regarding the spleen and it being fragile with MPNs.

It sometimes makes people a little too fearful of doing exercise. The spleen enlarged with acute illnesses from a virus, most commonly mononucleosis or mono, is an area where the spleen grows very quickly. It’s very fragile. And constantly, you hear about people having their spleens rupture with playing volleyball, or football, or what have you. And in MPNs, that really is much less of a case. It’s not nearly as fragile. And it really – it’s not a concern for rupture with all the sorts of normal routine things one would do as an individual with exercise.

Andrew Schorr:

Okay. So, Julia, have you had any worries about the kind of exercise you would do related to your condition, whether you’re gonna have a stroke, or bleeding, or maybe not bleeding, but other complications?

Julia Olff:

I think right after the TIA, and I can’t remember for how long, but maybe for a few months, I was feeling cautious about movement. And my platelets were not yet under control, so I was dizzy. And then they put me on Plavix as well, so that was sort of making it hard to do a lot physically anyway. Since being on Jakafi, having my counts much more controlled and having more energy from Jakafi, I don’t think I – I’m frankly jealous of other people that can do real exercise. I see people run past my window, joggers, etc. But I don’t feel like I have the energy to do that. So, for me, walking is really – walking and walking up steps are my physical activities. And the trips that my husband and I have taken really involve walking and the occasional swim in places that – you’re in sunny California, so maybe you have a pool. But, you know.

Andrew Schorr:

I have an ocean.

Julia Olff:

Yeah, and an ocean. That’s a lot of – to go into an ocean and deal with the forces of the waves, etc. To me, that would be too exhausting. So, I’m sticking with walking. That’s . . .

Andrew Schorr:

Yeah. Let me make a comment about exercise, just because I’ve been doing it for many years. So, yeah, after the marathons and all that. Esther and I go to the gym every day. And we joined one of these ones that’s open day and night. And we go, whatever our schedule is, and I get on the elliptical, and I do what I can. I watch the news, which maybe is a good thing or a bad thing. But at any rate – and I don’t beat myself up about how I did compared to the day before, or the month before, or whatever. But I just do it. And then sometimes, we run, and then we work in biking. So, that’s what we do.

And I would really urge people, because Julia, wouldn’t you agree, there’s a whole psychological benefit to just exercising or getting out there too?

Julia Olff:

Absolutely. And I know Dr. Mesa will – I’ve heard him talk about this, and I certainly read about, try to keep up to date, just talking about the news, about health information sources that reiterate things like getting yourself out. There’s something about stepping outside, and if you have some sunshine, and feeling that that helps, even when I don’t feel well. So, I feel like I always want to get out and move a little bit. And I just try to pace myself. And Julie was saying earlier, and I was thinking about there’s the physical activity, and there’s the amount of time I stand. I love to cook, so for me, being in the kitchen at 4:00 in the afternoon and making a two-hour recipe is a lot of fun.

But it starts to wear on me. And so, standing is a kind of form of exercise that you forget about.

Andrew Schorr:

Do you have a recipe you think – you enjoy making, and it’s an affirmation of better health for you? Something that you feel –

Julia Olff:

Yes.

Andrew Schorr:

What’s that?

Julia Olff:

I think the roasting vegetables. So, every vegetable tastes better roasted, I think. And I roast just about everything. And it’s so easy, because you can flip the oven onto 400 and go about your business. Once you’ve mixed with vegetables, Brussels sprouts, broccoli, different kinds of earthy potatoes, sweet potatoes, and olive oil. Light on the salt, pepper, garlic. And it’s good stuff, and it’s easy.

Andrew Schorr:

Okay, Julie, I have some questions for you, because again, it’s in my daily life, maybe others.

And if you all out there in online video land have questions, please send them to MPN@patientpower.info, and our producer Jamie’s gonna forward some to me, and we’ll pose them before the end of the hour. So, Julie, we cook some things in a wok, and we cut up vegetables. And but my wife has started us using a little bit of something called ghee, which I think is clarified butter. So, how do you feel about that? Or should we be using some other oil instead?

Julie Lanford:

So, when it comes to fats, we like for people to have more of the unsaturated, sort of heart healthy fats, is what we think of, and less of the saturated animal fats. Less of doesn’t mean none. And so, there’s certainly room. I would say ghee and butter are similar in terms of their saturated fat content, as is coconut oil, which sort of has this health halo right now, but it’s still a saturated fat.

So, what I would tell you is it depends on the recipe. If it requires that you use a solid fat in order for the recipe to work, then I would use it. If you can use olive oil instead, or canola oil, or peanut oil, I would choose those. And so, as long as you’re getting a variety. But if you’re always using butter or coconut oil, or if you are somebody who heard coconut oil was healthy and switched from olive oil to coconut oil, we wouldn’t really recommend that. So, it’s really more about the balance, and also how much of it you use. Now, if people are using it so that they will eat vegetables, I think that it’s still an overall gain, because we want people to eat vegetables. And talking about roasted vegetables, nobody’s gonna eat something if it doesn’t taste good. I don’t care how healthy it is. So, we need for you to figure out ways that make healthy food taste good. And so, we try to balance that when we’re giving those recommendations, but you know.

Andrew Schorr:

Okay. I’m gonna skip back to exercise for a minute, related to sort of mindfulness as well. So, Julia, you told me that you were actually in a yoga study. Is that right?

Julia Olff:

Yes, one that Arizona State and Dr. Mesa’s team was running. I was in a control group, so I didn’t get to initially participate, but they were – and hopefully, Dr. Mesa will share the results, but they were looking at the benefits of yoga for people with MPNs.

Andrew Schorr:

Okay. What about it, Dr. Mesa?

Dr. Ruben Mesa:

So, yoga is something that has been found to be helpful in a variety of diseases. And in particular, it’s been primarily studied in breast cancer. So, we wanted to help to demonstrate really several things as an evolving arc with my colleague Jennifer Huberty that leads kind of this exercise research activity at Arizona State.

So, one, we wanted to prove that yoga can be helpful, that yoga has several components, both physical activity as well as a meditation component. And we wanted it to be something that people could utilize really at their homes. And much of the yoga research done in cancer patients or others has been a bit artificial, with people having to travel into the city to go to a center that wasn’t very feasible. So, we’ve completed two studies and seek funding from the National Cancer Institute for the third. The first study, we developed a series of yoga modules to be done at home, in partnership with an online yoga instruction company called Udaya. And what they do is they develop yoga modules to have people do yoga at home. Well, we taught them about MPNs over a couple day period of time. And they created some modified yoga specific for MPN patients.

So, the first study we had was a feasibility study, which we published in the medical literature, where we showed that in about 30 patients, we found that they could figure out how to use the modules, that they used them, that they could use them safely. But whether there was really feasibility – is it feasible? And in that small group, we were able to show that there was also some benefits. They felt better, they felt better, they slept better, they had improvements in fatigue, etc.

The second study was the study that she just mentioned, that was yoga versus a control, where people were on a waitlist, and then after the period of time, they then could use the modules.

And in that study period comparing the two, in addition to measuring the impact of the yoga, we also were measuring blood levels of different levels of inflammation-related proteins or cytokines in the blood to see what sort of impact, in addition to sleep, fatigue, symptoms was having on the biology of issues of inflammation. And we’ll be presenting next week at the American Society of Hematology some of those results. But what we found is, one, not surprisingly, we think yoga is helpful. And it helped with fatigue. It helped with issues of mood and depression. And I think consistent with what’s being seen in other areas, one of the major benefits of yoga might be enhanced sleep. It is one of those potential benefits of yoga. Two, there are, again, the two components. There’s really an activity part with the poses and things of that nature, and is that better or worse than doing an elliptical machine? I don’t think that’s been studied.

But there’s that part. But then there’s really also a meditative part that includes breathing, balance, etc. So, I think there’s a variety of parts, and we’re working to study these different parts. We’re looking to study, how do we take people who have really not been active before? How do you get started in yoga is a little different than having people that have already been fit in the past, and really look to better understand these things so that we can really move to a place where they can be a resource for MPN patients, but also so that physicians know how to recommend or utilize tools like yoga for appropriate patients.

Andrew Schorr:

Yeah, I can’t wait to hear more about it at the ASH conference that’s coming up. And we’ll be covering it, so we’ll look for that. So, we started getting some questions. This one’s from Susan. In recognizing that there will be some patients who will need a stem cell transplant with myelofibrosis, we might progress to that.

And certainly, I know people like that. Julia, you may too. So, two questions about that, Ruben. One is, is there some physical conditioning you should do if you know you’re gonna be headed for a transplant? And second of all, what about recovery? In other words, will you do better with a transplant if you’re in better shape, and how can exercise be used to help you recover from the transplant?

Dr. Ruben Mesa:

Both are very good questions. Without question, physical activity with transplant is important. And people that go into a transplant stronger are clearly better off. But that clearly needs to be balanced with their physicians. What we clearly wouldn’t want is someone kind of wearing themselves out or trying to tackle too much in terms of exercise before a transplant either. You really want to go in kind of the best shape that you can.

Second, most transplant programs now really do try to, even during the process of transplant, try to maintain people’s strength the best they can. That might include everything from activities that are there in the hospital room or at the hospital. I’ve seen everything from kind of modified elliptical machines that you do while sitting down to other things. Without question, there will be days during the transplant people just don’t feel well enough to do that, and that’s fine. But the more days that people are active, really probably the better off they are. And on the backend, without question, whenever you have a very significant health intervention – I don’t care whether it’s a surgery, clearly a bone marrow transplant, anything that’s very dramatic like that, the process of active recovery, it’s a real process that, again, you’re starting a bit from scratch because you’re set back a bit with clearly going through a process like that.

But active recovery is key. People sometimes think, well, I had this big surgery, and it could be breast cancer. It could be a bone marrow transplant. And they think at the tail end, when they’re done, that they’re just gonna kind of bounce back to be exactly the way they were before when they started. And unfortunately, that’s not the way the body walks. You really have to kind of build that level of fitness back up again.

Andrew Schorr:

Hm. Okay. We’re getting questions about being a vegetarian. Grant wrote in and wonders – and I’ll pose this to you, Dr. Mesa, and also to Julie – Grant wants to know, is there any benefit to being a vegan or vegetarian when you have PV?

Dr. Ruben Mesa:

So, it’s a good question. I’d say, in short, I don’t think that there’s any evidence to suggest that you’re better off being a vegan or a vegetarian versus having a good healthy diet.

Are you better off being a vegan or a vegetarian than kind of a general U.S. fatty, salty, fried diet? Oh, absolutely. But compared to a general diet that has appropriate meat, and fish, and eggs, and other things, I wouldn’t say that there’s necessarily a big difference. Now, with PV, there’s always the issue of iron. When we do phlebotomies, part of the reason phlebotomies help to keep the blood counts controlled, specifically the red blood cells, is by making an individual iron deficient. And medicine sometimes can alleviate that, but it’s making people iron deficient. So, if you eat a lot of iron in your diet, particularly iron supplements, you’re really working at cross-purposes. You’re taking iron out by phlebotomy, but then you’re giving iron back in by a supplement. Doesn’t make a lot of sense. The amount of iron in the normal or a healthy diet is modest enough that we have not recommended the individuals to specifically avoid meat or natural food-based sources of iron.

We’re not trying to build their iron levels up, but nor do they need to have draconian avoidance of meat or iron in their diet. But no iron supplements.

Andrew Schorr:

Okay. And just so we know, Julie, was it spinach? Or what are some of the foods people often eat when they’re trying to boost their iron?

Julie Lanford:

So, the typical foods that we think of as really high iron foods are going to be more animal-based. Clearly, liver is sort of one of the top sources. Not many people eat a lot of that. But even clams, mussels, oysters, cooked beef tend to be the things that people think of. When it comes to the plant sources of foods and iron, they’re just not absorbed as easily. And there’s usually other factors that sort of inhibit the absorption of iron.

So, cooked spinach is usually picked up on as well, because you know what happens when you take a lot of spinach and you cook it, and it’s like down to nothing. Well, you’re eating a lot of spinach when you eat it when it’s cooked. So, those are things that I wouldn’t be particularly concerned about, unless your doctor has said you need to pay attention to your iron sources. What I would say when it comes to vegetarian diets, vegetarians tend to have better health outcomes because of that eating pattern of having more vegetables and plant foods in their diet, which has a lot of great nutrients. I think you can eat a plant-based diet that still includes meat if you want to. You don’t have to. It’s a pretty wide range of what we would consider to be healthy eating. But you would want to make sure that you’re getting labs checked. Plus, the nice thing about going to the doctor all the time is that they do kind of stay on top of your labs, so you would pick up if you’re becoming deficient in something.

For vegans, we focus on B12. It takes a long time to become deficient, but that can also sort of play into anemias and things. So, you would just want to keep an eye on that. I don’t promote a vegan diet, but I think if somebody wants to follow a vegan diet, I’m perfectly happy for them to do that, as long as they’re monitoring their labs.

Andrew Schorr:

So, Dr. Mesa, and well, Julia, I’ll ask you first. Julia, did you make any changes when you were diagnosed with what became known as a cancer? Like in my case, Esther had us getting distilled water at the house. But I mean, did you do anything like that? She had me stop drinking coffee. I don’t mean to blame Esther. We lived in Seattle, where Starbucks came from, but we made challenges. Oh my god, does that have something to do with the cancer.

Julia Olff:

Right. I don’t remember then making any significant changes. I do feel like over time, and the more often I’m hospitalized, the more kind of militant I get about avoiding things that make me sicker, like cigarette smoke. Hate walking down the street and having to suck in someone else’s smoke. But dietarily, I just try to have organic vegetables. We have a filter – we do have a filtered water system in the house. Just try to avoid poisons or toxins as much as possible. You mentioned coffee, though, and I wondered what – there’s more research in general out there about the benefits of coffee. For me, coffee, I consider it to be part of my medication regimen. And I’m barely functional until I have that first cup. I literally come down and have a cup of coffee to shower. And I wonder if there’s – if others feel the same way.

Andrew Schorr:

So, Julie, what about caffeine? And also, could you say something about wine, too? Because beer – so many different things. Drink wine, don’t. Red wine, white wine. This leads to cancer. Who knows?

Julie Lanford:

Yeah. Everything, right? So, when you look at actual data – and I rely a lot on the American Institute for Cancer Research, who reviews every study that’s been done. And so, they come up with great recommendations and very commonsense, so I like that. They have tea. So, a lot of people have heard green tea is really good. So, yes, it is. But they also have coffee on their list. Now, the way you have the coffee – Andrew mentioned earlier, syrup in it – that’s why I tell people, if you go to Starbucks and you get four pumps of syrup in your whole milk with whipped cream on top mocha, that’s a dessert. But if you just brew coffee at home, and you put a little bit – I just use milk for mine – that’s perfectly healthy.

And it does have plant nutrients that are good for you. So, I consider it healthy. If you’re sensitive to caffeine and you know that it keeps you up, or whatever, you can get decaf. Or if you just don’t like coffee, drinking tea can give you great benefits as well. When it comes to alcohol, we do know that alcohol increases risk for cancer. I will say, that’s when you drink it regularly. So, that’s when we see people exceeding what we recommend as moderation. And so, if you don’t know the definition of moderation, I’ll teach you that. One drink a day for women, two drinks a day for men. I know, it seems not fair to us women. But that’s what we would say is moderation, and you don’t get to save those up for the weekend. Just because you’ve missed it all week, you don’t load up on the weekend and expect that to also meet the definition of moderation. But if you’re less than that, we consider it to be fine. Although when they said that red wine was good for the heart, they sort of backed away from that more recently.

 It’s the skin of the red grape that’s really good for you. So, it turns out, you can eat grapes. So, that’s my point on that.

Andrew Schorr:

Good advice. Dr. Mesa, we’ve gotten in a couple of questions I wanted to pose to you. One is from Dave and Karen. It says, does exercising affect blood test levels in any aspect? So, let’s say you were a runner, or biked, or went to the gym or something, on the day you were then gonna come to your clinic for a blood test, would the blood test be accurate or changed based on the exercise you just did?

Dr. Ruben Mesa:

It probably does impact it to a modest degree. Probably not to a significant degree. So, it might slightly increase the white cell count or the platelet count in kind of that immediate post-exercise period. And clearly, if someone were to be dehydrated, that will make the red blood cell count seem a little bit higher as well.

So, it can kind of both concentrate the blood a little bit, if you’re dehydrated, as well as if it’s really significant exercise and leads to any inflammation, might slightly boost up the white cell count or the platelet count. But again, talking modest levels. A 350 platelet count going to 400, not 350 going to 1.2 million. So, modest increases.

Andrew Schorr:

Right. And all the doctors have told me, you all look at the trends.

Dr. Ruben Mesa:

Correct. Correct. Absolutely. And for most regular spurts of going to the gym exercise, probably it’s not even noticeable. But if somebody again did an Iron Man triathlon, you’re gonna notice changes in the blood.

Andrew Schorr:

Okay. Well, here’s a guy who’s pretty busy. Mark writes in. He says, I do an hour and a half every morning, stretches, planks, yoga, and even sun salutations. Sometimes I feel slight strain in my large spleen, but it’s never severe and always goes away.

So, he says, on a one to ten scale, Dr. Mesa, how much am I endangering myself, if at all?

Dr. Ruben Mesa:

You know, probably a two out of ten, from what it sounds like. Again, it may be more muscle strain, and it probably really isn’t injury of the spleen. But again, this particular activity that really causes muscle strain in that area, I would probably just modify the activity. Again, a very enlarged spleen is different anatomy than even we were kind of built to have. It’s much larger than normal. It’s asymmetric, so accommodating your exercise for that is appropriate. I would probably look at modifying the stretches if the stretches are irritating that.

Andrew Schorr:

Mm-hmm. Okay. So, one of the things I’ll just point out to people – and you mentioned it earlier, Dr. Mesa – is have a conversation with your doctor about where you are, how you’re feeling, what medicines you’re taking, what you like to eat.

And there are people who can help – now, Julie, you have a website where people can send in questions to you. What’s that website?

Julie Lanford:

Yeah. It is cancerdietitian.com, and it’s part of our nonprofit, so there’s no fees or anything.

Andrew Schorr:

Okay. Now, that’s very helpful. So, Julia, do you recognize that we with an MPN are sort of a moving target? That whatever is normal or feels good to us may change over time. We have to accept that, but that’s part of our dialogue with our healthcare team as to exercise, diet, medication, what’s right for us at that, point? It’s not static.

Julie Olff:

Absolutely.

Andrew Schorr:

I feel that. And that’s where my dialogue is with my doctor. So, just one last thing. I want to make sure I heard you right, Ruben.

So, contact sports – so, should I worry about biking if my platelets have been lower? That I’m gonna have some accident and I’m gonna bleed to death on the road or something?

Dr. Ruben Mesa:

Well, I would say, with 40,000 platelets, I probably would not do kind of the off-road trail cycling with high likelihood of running into rocks or things like that in Arizona, where it can be a bit treacherous. But if you’re really thinking about more gentle cycling, road cycling, particularly if you – and appropriately – are wearing a helmet, it’s probably fine still at that range. At 40,000 platelets, most individuals, even with fairly significant trauma, will still have the same reasonable clotting as other individuals. One probably could have emergency surgery at that level, barring really extreme trauma.

Andrew Schorr:

Okay. And the reverse is, if you had really high platelets, and you’re worried about stroke and other things like that, you’re still not worried that somebody’s gonna run around the block, and that’s gonna put them over the edge?

Dr. Ruben Mesa:

I think that’s highly unlikely, without question. Again, whether they’re high and they need treatment or don’t need treatment, clearly it’s a discussion between the patient and their physician. But in general, appropriate exercise with adequate hydration, or clearly exercise that people have really evolved into, as opposed to a dramatic change in activity level, is usually quite safe.

Andrew Schorr:

Okay. Well, I’m gonna try to work yoga into what I do. My balance is terrible, but I’m gonna try to do – what is it, downward dog, if I can. And they do it my gym, so I’m gonna try that. And Julie, just as far as diet goes, people can write you.

And again, cancerdietitian.com, right?

Julie Landon:

Yup.

Andrew Schorr:

And I think, again, I mean, it sounds like a broken record, but we talk about the healthy diet, fruits, vegetables, some protein, some meat balance, and not crazy about supplements, right?

Julie Landon:

Right, yeah. Unless there’s a reason that you would need a supplement, I don’t think that the general person just needs to be on one. If you like the idea, a multivitamin that should not break your bank would be fine, and you could even do that every other day, and still, it’d be fine. But it’s not necessary, as far as I’m concerned.

Andrew Schorr:

Well, I want to thank both of you for being with us. So, Julia, as we wrap up, and you’ve been listening as a patient as well and living it, what do you take away from this?

Julia Olff:

I guess I’m thinking about it very personally, that I feel like I’m on the right track. I’m trying to do as much as I can to be well,  and to be well around a disease that we can’t control.

Andrew Schorr:

Right. Well, I have a great – I think, for all of us. I have a good medical team. People like Dr. Mesa, people that may be at your clinic, like Julie, who can help with diet. Social workers as well. And also, you said it earlier, Ruben – accept that normal for you changes, that we do have a condition. I mean, we even refer to people with extreme interventions like a transplant, that you’re in a recovery mode, and you do what you can. And but doing something is a benefit.

I want to thank you all. Dr. Ruben Mesa, I’m gonna see you at ASH coming up. And Ruben, thank you so much for joining us, once again.

Dr. Ruben Mesa:

A great pleasure to be here. Thank you. Great discussion.

Andrew Schorr:

Okay. And Ruben, thanks for your devotion to all of us and to research. We really appreciate it. Julie Lanford with Cancer Services in Winston-Salem, North Carolina, where I spent like 12 years of my life, in North Carolina, thank you so much for being with us, once again.

Julie Lanford:

Thank you for having me. It’s been great.

Andrew Schorr:

And Julia, I’ll see you back in New York City one of these days.

Julie Olff:

All right.

Andrew Schorr:

But I want to wish you all the best. And you and I are on a journey with myelofibrosis now. But every day is special. But we hope we have a lot of them. And enjoy your family and your grandchild. What is her name, Elaina?

Julie Olff:

Elaina. Yes, I’ll see her for the holidays.

Andrew Schorr:

I’m looking for grandchildren, so you can give me pointers. But all the best to you.

Julie Olff:

It’s fun.

Andrew Schorr:

Yeah. Thank you so much.

Julie Olff:

You get to give them back.

Andrew Schorr:

Yeah. Thank you so much for being with us. And I just want to mention to our audience, Dr. Mesa referred to it, the kind of World Series of blood-related conditions is the American Society of Hematology. And there’ll be 25,000-plus people there.

And we’ll be there with our team, getting the latest information and bringing it to you, even some live broadcasting. So, if you are not a member of patient power, go to patientpower.info, sign up for the ASH daily updates. And whatever there is about MPNs, we’re gonna bring it to you. And there will be a replay of this Patient Empowerment Network program coming soon that you can share and go over again. Thank you so much for joining us. We wish everybody the best of health. Go out there and do what exercise that you can. A little more is probably better. And think of yoga, and also that balanced diet. I’m Andrew Schorr in Carlsbad, California, feeling good about things. Remember, knowledge can be the best medicine of all.

Living Well with MPNs – What YOU Can Do to Advance MPN Research

What YOU Can Do to Advance MPN Research

Living Well With MPNs – What YOU Can Do to Advance MPN Research from Patient Empowerment Network on Vimeo.

An audience of MPN patients and their caregivers joined us online or on the phone as experts discussed what patients can do to advance research and to raise awareness for MPNs.


Transcript:

Beth:

It is Blood Cancer Awareness Month so our webinar is what YOU can do to advance MPN research. I’m Beth Probert. I am a polycythemia vera patient and advocate.

I was diagnosed with PV in April, 2016 and I had about 12 months of treatment which included a few phlebotomies and interferon, Pegasys. I reacted very well to Pegasys and I am now in remission. I get my care at the University of Southern California Norris Cancer Research Center in Los Angeles. I’m coming to you live from Oxnard, California, which is just north of Los Angeles on the central coast.

I would like to start off by thanking our Patient Empowerment Network for their support, and the MPN Research Foundation for their continued partnership.

I’d like to welcome our guests today. We’ll start off with Dr. Verstovsek, who is a renowned MPN expert from The University of Texas MD Anderson Cancer Center. Thank you for joining us today, Doctor.

Dr. Verstovsek:

It’s my pleasure. Thank you very much for having me on the program.

Beth:

And I’d also like to introduce you to Lindsey Whyte, from the MPN Research Foundation. Lindsey, thank you for taking the time to join us today.

Lindsey:

Thank you so much for having me. I look forward to enjoying this esteemed panel.

Beth:

Thank you. We have two patient panelists today joining us. Both have been in clinical trials and both run support groups in their area. Our first patient panelist is Nick, and he’s coming to us from central Florida. Thanks for joining us, Nick.

Nick:

Thank you very much, Beth. Appreciate it, glad to be here.

Beth:

Great. And I’d love to introduce Andrea, our other patient panelist. And she’s coming to us today from Dallas, Texas. Thanks for joining us, Andrea.

Andrea:

Hi everybody, it’s great to be here. Thank you.

Beth:

Great. I’d like to start off our program today just getting to know a little bit more about Nick and Andrea. Nick, I’m going to start off with you. You were diagnosed with myelofibrosis in February, 2016. Let’s talk about when you were first diagnosed. What was your first move after diagnosis?

Nick:

Definitely I was quite shocked. I was asymptomatic, and the doctor who presented me with the diagnosis really didn’t give me a whole lot of information; basically a Google printout that said I had one to three years to live. So, I traveled throughout the country, hooked up fortunately with Patient Power and MPN advocacy; went to a seminar in Stanford, outside of San Francisco with a wonderful group of doctors there to really learn about the disease.

Ultimately went to May Clinic, Dr. Tefari; Hutchinson Clinic, Dr. Mesa in Scottsdale, Arizona; and finally spent time with Dr. Pemmaraju who works with Dr. V. at MD Anderson. I felt it was important to try to learn as much as we can about the disease to try to help other people behind us, so I signed up for a trial with azacitidine and Jakafi at the MD Anderson hospital, which was phenomenal. They did a wonderful job but unfortunately my blasts had spiked up and I had to go to transplant, which I did a transplant on January 15 of this year.

Beth:

Wow, you have really been through quite a lot in such a short period of time. We’re definitely going to come back to you and talk about some of those details you gave us more specifically. Thank you.

Nick:

You’re welcome.

Beth:

Andrea, I’d like to go to you, now. You were initially diagnosed with essential thrombocythemia about 19 years ago, and then you were later diagnosed with myelofibrosis about nine years ago. So, you’ve certainly had quite the journey. I’d like to hear a little bit about how you reacted when you were first diagnosed.

Andrea:

Sure. My primary care doctor was really great in seeing that my platelets were rising. And while they weren’t that high, she still sent me to a hematologist just in case; a local person here. He did know about it but wasn’t too versed in the MPN world, and we worked together and I was on anagrelide and a couple of drugs and I was doing great, no problems. My platelets were good; everything was great for ten years. And then, things started to change. I started getting tired. And the first thing he said to me was, I think we ought to send you to MD Anderson.

When I had essential thrombocytosis, I felt fine. Emotionally I was fine because I had no symptoms. But when it started to convert, when things started to change and my lifestyle changed and I got much more tired and of course anemic, that was emotionally difficult. But then I went to see Dr. Kantarjian, and soon Dr. Verstovsek, who started me on different trials, I said I am not going to sit here and die. Because I got the same thing; five to seven years, not from any of the doctors at MD Anderson, let me clarify. But I knew that it was at that point kind of a death sentence, not to be dramatic about it.

But I was not going to sit back and let that happen. So I said, what can we do? And was told let’s start you on a trial. I’ve been on five. Three of them didn’t work. One emotionally almost killed me; it was not fun at all.

But the last two, I guess I could say I was in remission. I never heard the word from Dr. V, but I felt great. My life was going along fine. The last maybe six or eight months, the drug seems to not be working as well and we’re looking for something else, possibly stem cell transplant.

Beth:

You’ve had quite a journey over about 19 years, so I’m guessing you’re really a guru to a lot of us; myself, being newly diagnosed compared to you. And I know that both you and Nick run support groups. And if I can ask you, since we’re talking right now, can you tell me a little bit about your support group and then Nick, I’ll go to you in just a few minutes. Your support group is in the Dallas area. Can you give me a little feedback about it?

Andrea:

Sure. It was actually started by someone, Karen Stern, a good while ago; I don’t remember exactly when. Unfortunately, Karen got very sick very suddenly and is no longer with us.

She had asked when she was ill if I could take it over for her. I said absolutely, I’d be happy to do that. So, we meet quarterly. We have anywhere from 15 to maybe 30 people that come. We talk about what’s new with us, what’s new with our symptoms, what reading we’ve done, how we have learned, what we’ve seen in all the different conferences, and we share a lot of information. We eat, we have a glass of wine, and it’s great fun.

It’s wonderful to be hooked up because as much as I think I try to keep up with the diseases, I learn something from people at our support group. What’s hard is when people don’t come anymore for reasons that they’re sick or other reasons, and that’s tough on the group. But it’s all part of the process, I believe.

We have a lot of communication; we talk to each other. We use Facebook and we learn.

Beth:

Wow, and it sounds like you guys have a really personal group there and happy; that in-person connection sounds wonderful. Thank you. Nick, tell us a little bit about your support group in central Florida.

Nick:

It’s definitely a little looser organization. We have probably an email list of about 15 people. We keep adding just about one person every other month or so. Unfortunately for me, we got the group together and I started just doing the emails, sharing information with people, guiding them to Patient Power, guiding them to MPN. A lot of them are trying to find doctors in smaller towns in Florida where they don’t have access to people like Dr. V, and so trying to steer them to some of the better doctors in the area.

Unfortunately then I was going through a transplant so I was kind of out of pocket. So we’ve not had a chance to physically meet. We are kind of spread out; we have people in Jacksonville, Orlando, Tampa, Miami, and Naples.

So just with my regrouping here after the transplant, we’re hoping to probably in the next month or two have our first face-to-face meeting and get some folks together, probably in Orlando, and try to get the group together. But so far, it’s just been a matter of emails; folks emailing each other back and forth. We do have a lot of it seems like mostly PV patients, and they will share different techniques and just like Andre was sharing, some of the things she’s been through. I definitely feel that being around other people who are in the same boat is so much more powerful because it’s hard sometimes to talk to your family members or friends or people at work because they just don’t get it.

They don’t understand what you’re going through and how scary it is. They can’t really give advice. So we’ve found that the support group has really been – it helps me as much as being a part of it is feeling better about what’s going on. It is kind of sad, too, as Andrea said as you see some of the folks take a turn, and you’ve got to kind of rally everybody together because it is – unfortunately, this group, it’s folks who are sick and they’re all going to have their ups and downs and we have to kind of be there for each other. So, it is one of the tougher parts of being a part of a support group as well; I agree with Andrea.

Beth:

I can definitely imagine. Just hearing from both of you and my own experience being in a support group, whether it’s in person or whether it’s online or through email, they’re just all equally effective and really sometimes the best medicine for us; a certain part of our care. I’d like to shift gears a little bit, and Lindsey I’d like to talk to you a little bit with your expertise in the field. Patients are newly diagnosed and you know, how do you convey to them the importance of educating themselves and their family and their friends? What would your message be?

Lindsey:

The MPN Research Foundation has extensive information on our website, and also when somebody registers through our online system.

And I’m not talking about the registry; just contacts us initially, we send out packets with information and we will customize those packets according to a specific patient’s need. We also do or best to hook people up with local support groups or many times people come to us looking for a doctor or a specialist, and we’ll point them in the direction of online resources or others who may be able to help them locally. We have lots of resources available to patients through our organization, and also on our website and to the extent that we can help with a specific question, then we usually try and point someone in the direction of someone else who can.

Beth:

I have to say that that’s exactly what I did. I found your website when I was newly diagnosed and I registered. I got my packet. I was so excited, it had a lot of great information for me. I also got some wrist bands, and I just felt connected.

It was one of the first organizations I found and it just really gave me a sense of really being connected. So, Dr. Verstovsek, I would like to talk to you a little bit about how do you advise your new patients about identifying trustworthy info as far as… we could all go on the internet and go willy-nilly. I was convinced I was dying after two minutes on the internet. But you must get a lot of that. You must get patients asking you what do I do, how do I get information; how do you guide them?

Dr. Verstovsek:

Just towards my endorsement of what we have discussed so far in terms of education and the patients’ engagement, I have seen some of you in my own clinic and you know very well that to every new patient, because this is a chronic disease or diseases, the patients have to be engaged.

And I always endorse them to become a partner in what we are trying to do together to control the disease and eliminate the problems, and make people enjoy life fully for as long as possible with a good control in signs and symptoms. And therefore, engagement and partnership with your doctor and self education through support groups, through symposia, through pamphlets through web is increasingly important. Because the decision-maker is the patient, after all. The doctors are here to support.

And if they can partner together throughout their lives and become good friends, and I always seem to joke about it; we become good friends for the rest of the time. We actually do, and we engage together and we try to educate each other. I learn from the patients, patients learn from me and we go through life together. And so an educated patient is the one who is the best patient because we can participate together. And the sources are increasingly available to all of us.

What we are doing her today, Patient Power on the web, MPN Research Foundation through the web, through symposia, through pamphletsthrough educational material, participating in patient symposia through educational foundations; those are also available apart from MPN Foundation. And then going to the academic centers and their websites; MD Anderson, Mayo Clinic, University of New York City. There are a number of very well established academic centers that have very nice academically-driven websites for education of the patients.

It’s not necessarily to engage at the professional level where the doctors would go and educate themselves about these rare conditions, but also the patient side of the academic sites are very well informative for the patients. This is where you get up-to-date information from very well established professionals that are engaging in education of the patients.

Plus, what you have described, Nick and Andrea, engagement at the personal patient level; support groups aerospace increasingly important for the understanding of the complexities that we are facing and understanding the diseases, and understanding the therapies and the different outcomes. Look at yourselves in this panel. We have a patient, Beth, who is an example of an extraordinarily response to a therapy in complete remission.

Nick had a progressive disease, ended up having a transplant; and Andrea has lived so many years with the condition and went through the different therapies with different outcomes and is living now way more than what her first doctor said about myelofibrosis; nine years and going very well. So, people are different. Things are improving markedly and we need to work together, and education is the primary source of that effort.

Beth:

That is fabulous. I could really see how your really personal approach to caring and educating your patients really allays their fears. I wore those shoes where I was scared, and I really admire the way that you help your patients understand what is out there for them and to see the positive approach. Dr. Verstovsek, why do you feel an MPN specialist is so important when we have patients like Nick and Andrea and myself and others out there, as opposed to just kind of avoiding the specialists? What are the things that we should be really aware of and why we should go to an MPN specialist?

Dr. Verstovsek:

MPN diseases are rare diseases. And in many circles in academia, particularly essential thrombocythemia, polycythemia vera, ET, MPV are considered benign. Yet, we know that patients can change. Andrea has changed. There might be complications that can affect not just the quality of life, but the life duration as well.

Myelofibrosis is certainly much more aggressive and progressive, and can shorten life a lot but is the rarest of the free. So, myelofibrosis being so rare, people in a community setting, in smaller academic centers don’t have much experience. ET and PV, so-called benign conditions but not to me so benign, there is a need for education not just at the patient level but also at the level of physicians. There is much effort to educate professionals about the new developments in diagnosis, in therapy, and in prognosis of these conditions.

And therefore, a second opinion is always good to get. Wherever you are, even if you come to me as a first doctor, I encourage people, patients who come to me as a first doctor to seek a second opinion if it’s necessary to fulfill that educational potential that professionals can give so the patient is fully aware of what’s happening, and to live with that condition for the duration of time that there is.

The professional impact on the patient’s life is enormous because these are conditions that people live with. And therefore, proper indication and seeking a second opinion, and perhaps visiting an MPN specialist is highly encouraged

Beth:

Doctor, how do you coordinate care from afar? If it’s just not geographically… someone doesn’t have an MPN specialist near them, can you tell us a little bit about how you would coordinate that?

Dr. Verstovsek:

This is an excellent question because the specialists are around the United States and as you aid, not everybody can be local or come very often. And therefore, communication with the local doctor and education through the email or the phone is vital. We try to form a team. Patients at my center know that we are not here just to provide one-time opinion; it is continuous engagement with the local doctor.

And the patients are always encouraged to come back at the frequency that can be absorbed by their social and financial status; every six months, every 12 months if possible with more benign conditions. Or, with more aggressive conditions more often; engage in what they do, developing new medications or advising on the proper use of standard therapies. Because it is not easy even for a patient in a community setting to apply standard medications properly because of the rarity of these conditions, particularly myelofibrosis.

So, a team effort with the specialist, with the local doctor, and the third most important is the patient themselves; fully engaged in these three triangular here will provide the most benefit for the patient’s outcome overall. And that can be done as necessary. But one thing is that sometimes I should say expectations from the MPN specialist perhaps are overshadowing what actually the expert may do.

For example, myself, I am not able to monitor patients from a distance; it’s not advisable. Therefore, the local doctor must be part of the team with the interaction through the ways that I described for the best outcome of the patients. But not one doctor that can be supervising patients wherever they are.

Beth:

And that’s wonderful to know that this option is there for them. Because we do hear from patients who are in more remote areas and feel that perhaps are not getting the care for someone that’s really more renowned in their field. So it’s so wonderful to hear about those types of patient’s and how it can really benefit the patients. Thank you.

Lindsey, I’d like to ask you a few questions about the goal of raising awareness. Why is raising awareness essential to move forward, to really move research forward?

Lindsey:

That’s a great question. You know, as most people on the phone are probably already aware, the MPN Research Foundation is very involved in funding research and trying to help direct research for MPNs. One of the things that we really need to try and understand is the course of the disease and how we can help to affect the quickest results for the patients to help them to feel better. I don’t know if that answers your question, but that’s one of the things that we focus the most on, and that’s where our projects are directed.

Beth:

That’s great information. You know, I think people tend to forget that if we are such a rare group of diseases, the MPNs, and if we’re not raising awareness, we’re missing out. And we’re missing out in  moving that research forward.

Nick and Andrea, Andrea I’ll start with you; could you just give me some ideas, maybe? Has your support group or you, yourself personally, thought of different ways to get involved to raise awareness?

Andrea:

Well, one of the things we’re trying to do is invite speakers to the meeting. And my hematologist came once, and it was on a Sunday; I thought that was a very noble thing to do. People got great information. No holds barred, he answered questions and it was great. And hopefully we’re going to have someone from Cancer Care so that questions can arise, and then people can go and ask about them and check. How to raise awareness, I think it’s talking to people, I think it’s participating in maybe the LISTSERVs. It’s participating in things like this where they tune in and hear things and ask their questions.

I think it’s part of it on Facebook, encouraging people to go to meetings and to get more educated.

Beth:

Those are all great ideas. Nick, do you have a few ways or things that you’ve done either individually or through your support group that you try to raise awareness?

Nick:

Yes. I was kind of fortunate in that several years ago I was president of a company headquartered here in Tampa called Beef ‘O’ Brady’sWe had 270 sports pubs, kind of like a Buffalo Wild Wings. And then more recently I have a company called Little Greek, and we have 33 restaurants. We have five or six in Dallas and 17 here in Tampa. So fortunately the local media kind of got behind me and they did several articles about my disease, talking about myelofibrosis, trying to help us find – we signed up 700 Be the Match folks. Because I was trying to talk about the importance of getting people in this Be the Match database.

And then my wife did a blog going through the transplant process; she had over 10,000 hits and we actually set it up where it’s in book form where you can order it on Amazon and we’ve given it out to folks as well. So, we’ve definitely been pretty proactive here in the Tampa market with the Tampa Bay Times and Tampa Bay Business Journal and the Gulf Course Business Journal. They’ve been very nice about covering my experience and some of the ups and downs, and going into transplant when you don’t know if you’re going to make it, and how do you set up your business.

So we’ve been pretty fortunate. But it is such a rare disease, I have to explain myelofibrosis. They say what’s that, and I say it’s kind of like leukemia but red blood cells. I know my primary doctor said Nick, in 17 years you’re my only myelofibrosis patient and probably before I retire, you’ll still be my only myelofibrosis patient.

Fortunately, people like Dr. V. out there, his videos were so helpful for me early on, and I really do appreciate the senior physicians in this field. They’ve been so gracious with their time to get out there and help educate us. It really blew me away to have access to those types of materials because there’s so many questions.

I really appreciate him even being on here today; it’s so impressive.

Beth:

Great. Wow, Nick, that’s so encouraging to hear about how you and your wife got the community involved and really brought awareness to such a rare disease. Dr. Verstovsek, how broadly within the oncology community, how aware are they of MPNs? There seems to be other cancers and such that have a lot more attention.

Dr. Verstovsek:

Over the last ten years, much has been done on the awareness of these conditions for the physicians themselves. You may know that for example, one of the major meetings, the professional meetings in the United States is American Society of Hematology meeting that is always done at the beginning of December. And I tell you that ten years ago, there was no session on myeloproliferative neoplasms or MPN.

[00:49:00]                  

No educational sessions, no scientific sessions of significance of all; it was neglected completely. We changed the field completely from 2004 on by the discovery about what is problematic, the JAK-Stat pathway abnormalities, these biological abnormalities in all the patients and all the associated genetic abnormalities that leads to progressive disease. We changed the understanding of the disease. That led to development of new medications, developing new prognosis coding systems, improvements in our ability to manage patients. And now, I should be proud probably that it is not as fast as we would like, the MPN is at the same level as any other more serious conditions like acute myeloid leukemia. We have full fledged scientific sessions on MPN on its own, presentations, oral presentations.

I would say that people in the field, because this is relatively new, still, are hungry for information; the education sessions are full. Much more can be done on education of the physicians. So it is coming there, but it is a slow process, educational process on the patient side is in parallel being done to educational professionals.

Beth:

Wow, that is great. And it’s encouraging to know that the MPNs are getting the attention that they should be getting. Lindsey, I wanted to ask you, do you feel that focus on MPNs are being overlooked because of more prominent advocacy with these other conditions?

Lindsey:

I would say that it’s similar to what Dr. Verstovsek was saying. I’ve personally been at the American Society of Hematology meeting myself, and I’ve been at a lot of other – participated in some other meetings recently.

I’ve started to look more – obviously, given what I’m doing now with the registry project in the media, there’s definitely a lot more focus on MPNs than there probably once was. I also participate in some activities in Washington, D.C. having to do with the rare disease organizations there; there’s a few different rare disease organizations. So the MPN Research Foundation is trying to participate in activities like that to make sure there’s continued focus on MPNs there.

But you know, I think that we can never do enough, really, when it comes to a rare disease. We all have to play our part and keep it at the forefront of people’s radar because until there are better therapies out there, we can never stop.

Beth:

Wow, and that is great to know that the MPN Foundation is really getting more focus with the rare diseases and the work you’re doing in Washington. In fact now, I’d like to show a quick little video. There are a lot of people in the MPN community around the world that support MPN awareness and they’re doing great things. This short video will give you an idea of who those people are out there. So, I hope you enjoy this video for a few moments.

Beth:

Alright, so did you guys catch Nick in there? We’re hoping to hear from now we’re going to run out of slides because there are so many folks out in the community doing such great things, and that was real cool, Nick. Lindsey, I’m dying to ask you this question. myMPN Registry; we are all really super excited about this from the MPN Research Foundation. Can you talk a little bit and tell us what it is and what the goal is?

Lindsey:

Sure, I’d love to, thank you. So, as we’ve talked about on this webinar, there’s a lot of different experiences by each patient with an MPN.

Some people live with it for a long time, some people get a diagnosis that comes out of nowhere and it advances quickly. There’s lots of different paths that can be followed by an MPN patient. And one of the things that we’re most focused on, as I’ve stated previously, is to try and get some therapies that can help the patients regardless of where they are on that pathway. We said to ourselves, how can we better understand the pathway itself because each person’s experience is different.

People have different symptoms, they have… some of their symptoms are in their blood counts, some symptoms are more depression or they may have itching, they may have some other brain fogginess; different things. Everyone has different combinations.

So we wanted to understand that, and what we decided to do was put together what’s called myMPN. It’s a registry for patients to go in and share their experience. And in doing so, they can help to change the prognosis of all patients. Actually in the slides that you ran, there was a quote from Helen Keller and it talked about it’s not just one major mover or shaker; it’s actually everybody in the process along the way. That really encapsulates what is going on with myMPN.

We need patients each to go in and share their individual experience. We would love it if they would not do it just once but many times; keep coming back to the registry. So, the registry is structured so that we gather the information in a primary survey that has some history, background about an individual, their diagnosis, a little bit about their history and treatment, the drugs or therapies that they’re using.

But then there are additional surveys that we invite the patients to come back and fill out again and again, which collect information about what’s changing. So, there might be an event that has affected their health. Maybe they had some sort of a thrombosis, or a pregnancy, or it could be something related to their MPN or something unrelated. Then there’s another third survey called How Do You Feel Today, and that’s where we really want to understand the patient’s whole experience with the disease; how did they feel today versus how will they feel next week. Are they getting sleep, are they eating? Are they having a lot of fatigue, are they itching?

The idea is that for the many patients that we gather this information over a long period of time, then that will start to help us to understand the diseases better and over time, hopefully we can figure out if there are triggers to the disease advancing from one stage to another; trying to help to put together some of the pieces of the puzzle that currently aren’t available to researchers in the labs and in the hospitals.

We’re hoping to augment the research that’s already going on by helping to provide those researchers and doctors with day-to-day experiences of patients. So it’s a really great way to involve the patients directly in the direction that research is having.

Beth:

I think this is fabulous. Is this up and running now? Is it accessible?

Lindsey:

Yes. We launched actually earlier this month in connection with Blood Cancer Awareness Month. I’m humbled by the response; it’s just been fantastic to see how many people have really been involved and engaged and coming back to the registry.

Beth:

That is wonderful. How does someone get involved? How do they sign onto this?

Lindsey:

We have a dedicated website for the registry; it’s www.mympn.org. And on that web page they will see the link through to begin the registry process. The first thing that a user would do is set up their privacy settings. We liked the platform for this particular registry setup because it enables each patient to customize their privacy settings.

Some patients are very comfortable sharing the information about their health history and background, helping to contribute that information toward the scientific process. Some people just want to record it for their own future reference, and that’s perfectly fine.

Either way, we’re just glad that people are getting engaged. The system, myMPN system, actually does have that flexibility so the patients can determine what information, if any, they’d like to share with the researchers and the research process. That’s the first step; you set up your profile for your privacy settings, and then as I said, you start to go into the survey where you talk about your history with the disease. And then we encourage you to come back and fill out the other surveys on an ongoing basis.

Beth:

Great. Well, I signed up so I’m really excited that I can be a part. Dr. Verstovsek, I wanted to ask you, you’re on the steering committee of myMPN, one of the doctor’s registry.

What kind of impact do you think this is going to have for you and the way you practice medicine and make decisions and deal with patients over the next few years?

Dr. Verstovsek:

This is a very significant step forward. Look, what we know about the current conditions, like for example polycythemia vera. Let’s talk about polycythemia vera. You have in the literature assessment of the outcome of the patients that were referred to tertiary centers in the consultations. So they would come to Mayo Clinic, or to MD Anderson, or Moffitt or any other large academic centers. And there would be possibly let’s say 500 patients with polycythemia vera that were seen over the last 20 years.

Academicians would analyze them from the time they arrived and what happened with them with therapies, and you would come up with some knowledge. But that is such a small, small part of the larger community of polycythemia vera patients. There are possibly about 100-150,000 polycythemia vera patients living with the condition here in the United States.

And what does it mean to analyze the outcome of the 500 patients that were referred to you in academic centers? It means a lot, but not too much in the larger picture. So if we have a way of having a registry where multiple, multiple people, patients from – many patients from a larger group of patients, not just those that are seen in academic centers, can participate. And we can learn how they were diagnosed in a community setting; what did the local doctor do?

What symptoms did they acquire during their lives? What therapies did they receive, and why and what happened with those therapies? Any complications with the thrombosis? Any complications through the pregnancy? Those are the issues that are mentioned already. What led them to be referred to academic centers?

We can enlarge our knowledge, better our knowledge about the disease conditions; time to diagnosis, time to progression, management in community setting and the relevant new interventions and new ways of assessing needs of the patients, and understanding life with PV, or life with ET, or life with myelofibrosis on a larger scale and see where to intervene and how in the future.

Beth:

And in some ways, this really seems to overlap personalized medicine. We’re now not looking at the one scenario for PV or myelofibrosis or ET. We are looking at hopefully a huge group of MPN patients and putting those pieces in the puzzle, as we said Lindsey.

Dr. Verstovsek:

And let me add – this is really good. This is an excellent comment. Because we these days think a lot about the genetic complexity. There are patients with myelofibrosis or any other conditions that differ based on genetics, as I mentioned earlier on. But there are patients with myelofibrosis that present with anemia only, patients that prevent with very big spleen and poor quality of life.

There are different ways of people progressing or presenting with a condition not only based on genetics. What is the experience of patients that have only low blood cell count versus those that have a very big spleen; how did they fare? It’s clinical assessment and quality of life assessment and blood cell count assessment. We don’t really need to engage in extraordinary tools to learn. Genetic is one part of it, but it is much more we can learn from our on practice on the larger scale.

Beth:

Dr. Verstovsek, is there really a difference between this and an observational study?

Dr. Verstovsek:

There is some difference in that observational studies are usually much more focused in a shorter time period in a selective group of patients, in academic centers usually, with much more scrutiny of the detail. So, if you have an observational study in polycythemia vera, since we’re talking about polycythemia vera, there is such a study; it’s called the REVEAL study. There is also observational study for patients with essential thrombocythemia and early stage myelofibrosis called the MOSS Study.

So, a limited number of patients with very dedicated focus to see patients periodically, collect all the data of what happens to them all the time, because they are followed by clinicians and the researchers and nurses; this is a full fledged clinical study. Without intervention, just to see what happens with them; what symptoms develop, what complications they may have with other medical problems, what happens when they’re hospitalized and why, what the reasons are for intervention for their disease.

What is the effect on their work, ability to communicate with the family, engagement in social encounters. So it’s much more focused, perhaps more in detail and in a short period of time. But it does very well complement the registry, which is much broader and for a much longer period of time. So, I encourage patients to participate in both efforts.

There is complementation between the two, and certainly encouragement from the academic and local doctors to learn from these efforts.

Beth:

Doctor, what is the criteria to participate in an observational study?

Dr. Verstovsek:

Unlike the registry where really we are trying to include everybody who has the disease at different stages to see what is happening with them, registries are usually focused on the patients like the Moss Study; I mentioned it’s for patients who have essential thrombocythemia that requires therapy; and for patients with myelofibrosis that do not require therapy. So it’s a concerted effort to understand much better in detail particular groups of the patients. So there is eligibility criteria for participation in some of these observational studies, unlike the registry where we really like to have everybody.

Beth:

Alright. And of course now this leads me to clinical trial. We hear a lot about clinical trials. Could you briefly describe for us the difference between a clinical trial and an observational study?

Dr. Verstovsek:

Absolutely. And see, while I was giving an example of an historical analysis of patients in academic centers that leads to information how to manage patients and what to do about them. But these are the patients who are referred to academic centers, usually – most of the time – because they are not doing well and there is a need for intervention. And most of the time, we talk about treating patients that need to have something corrected.

They suffer from anemia, they suffer from a blood clot and this is where we intervene, and this is where most of the work in academia is focused on. This is where we do clinical studies. Clinical studies in MPN, most of the time and in the United States in particular, are focused on correcting something that is wrong; improving quality of life, decreasing the spleen, improving the anemia in ET or PV.

We would like to treat people for what they suffer from; high platelets, high red blood cell count, big spleen, symptoms. Intervention studies in myelofibrosis for example are needed as we try to prevent another clot in patients with ET and PV. So we are moving from interventional studies to prevention studies. And to get proper assessment of those patients in need, observational studies are needed to learn about the experiences.

A registry is needed to learn about a wide spectrum of patient experiences for us to identify groups that would, for example, benefit from prevention rather than waiting for them to suffer and then prescribe something to correct it. So prevention studies will be major developments, in my view, from observational studies to see where we need to intervene once we observe.

Beth:

Very interesting. I had not even heard of that. That is fabulous.

Both Nick and Andrea, you have both participated in trials. And Andrea, I would like to go to you first. You’ve been in several clinical trials. What was your journey, and what was beneficial in participating in those?

Andrea:

Well, frankly the whole point of my participation was not only to feel better and maybe arrest the disease to an extent, but I felt since it was such a rare disease I had an obligation to try to advance research by using me as a live guinea pig. Instead of donating my body to science later; let’s try to do something now. Of course I had selfish reasons, as well. What happened with the early studies which were done nine years ago or so, several of them just were very toxic for me, and for different reasons.

But different things happened; a couple landed me in the hospital. But I knew there was something out there, working with Dr. Verstovsek, working with my local hematologist; I knew that if I didn’t try and didn’t do things, that I certainly wasn’t going to get any better. So, when we hit on CYT387, which I bugged Dr. Verstovsek about because I read about it, and I said it sounds right for me; he said yeah, I’m gonna get it, I’m gonna get it.

He finally did. It worked for five years. The company was bought out by another company. I have a similar drug; it doesn’t seemed to have worked as well but for five years I’ve been transfusion independent, which is huge.

While my anemia has not been anywhere near normal, it’s certainly functional and I’ve been great. Now we’re looking for something else. I’m a perseverant person, and the first couple of trials didn’t work but I didn’t die, and I didn’t get any worse. And the fourth and fifth trial did work, so I think I have to encourage people to not give up. We’re all different, and we talk about that in our support group. Everybody is different. We are so individualistic in this disease that we can listen to other people, but we have to really listen to our bodies and ourselves.

So now, it’s that period of kind of treading water; what do we do next? There are some things that Dr. V has mentioned, there are some things that I’ve been reading about that I’m going to quiz on him when I see him next. And so it’s a little discomforting right now because something has to happen.

 But I’m confident and positive that there will be something out there, but if I don’t try, we’ll never know and a patient behind me – we have people in our group who are 20 years old and 30 years old. They’re panic-stricken. So hopefully I can help them, maybe; if I don’t someone else does.

Beth:

You know, Andrea, you’re very inspiring. Me kind of being new to the game, too, it’s very inspirational to hear about your perseverance and your attitude. I love the idea that you’re also there for the younger people in your group to show that this is the journey but it’s working, and there’s hope on the horizon. Nick, if you could tell us a few things, a few thoughts about your journey through your clinical trial and if there was a benefit?

Nick:

Yeah, sure. It’s kind of interesting for me initially when I was diagnosed, the local doctor said well, you’re so lucky; you have Moffitt right here in your backyard. So I went to Moffitt Cancer Center, and they’re very good but the hematologist said basically the same thing that the initial doctor who did the diagnosis; well, you’re a good candidate for transplant, just wait a year, watch and wait a year and then go to transplant and so be it. But you do the research, and transplant is a pretty tough deal.

When I went to Moffitt, basically that’s what the doctor said, is we’ll see you once a month or every other month and sometime next year you’ll go to transplant. I said doctor, I can’t just sit around and wait and just sit back and placidly have this ticking time bomb hanging over me without trying to do something. And like Andrea, I also felt I owed it to the other patients that maybe being part of a trial that we’ll learn something.

I was hoping – my goal was to try to postpone my transplant for several years. But I said being part of the trial, maybe they’ll learn something good or bad that will help other patients as well. And that’s where I was very fortunate to land at MD Anderson with Dr. Pemmaraju.

They set me up on azacitidine and Jakafi. Moffit’s pharmacy doesn’t even carry Jakafi. So, the No. 1 tool in the toolbox for MPN patients, they don’t even have it there. That’s where we did the trial, and I think with the trial the one thing that people need to know, you’re under a much higher level of scrutiny. Dr. Pemmaraju at Moffitt, they’re having me come in every 30 days for blood work, 60 days to visit with the doctor. Pemmaraju, he’s seeing my stuff every week; they’re looking at my numbers. I go fly out there once a month to meet with them.

And so you have an extra layer of coverage. And ultimately, it was Dr. Pemmaraju who said hey, Nick – by the way, CAL-R, JAK2 was my mutation, which also people need to know who’s doing what. But in October, Dr. Pemmaraju noticed my BLAST had spiked from 1 to 5. He said Nick, you’ve got to go for transplant because if it turns into AML, your prognosis really gets a lot worse.

And I’ll always remember the look on his face. He just looked at me and said, time to go. That’s why I think his higher level of watching me gave me that sense because there is some controversy out there as to when to go to transplant. When do you go? Do you wait? Is there a certain number you have to hit?

I felt that his advice, based on all the doctors I had met with, was very right on point and I appreciated their – there’s a great group of folks there, and I certainly think that my success – and I don’t know if Dr. V. agrees, but me being on Jakafi, actually they kept me on it through the transplant; I think that helped me because I’ve had a fairly good transition through the transplant process. And I think it was based on the work that Dr. Pemmaraju did.

Beth:

Great. Nick, you’re very encouraging. Dr. V, since Nick brought that up, how do you feel about that, that he was kept on Jakafi?

Dr. Verstovsek:

I would say that both Andrea and Nick have amazing stories to say and to tell us their experience and to learn, and really inspiring stories. I’m glad that there was a time period to enjoy some good quality of life and control of the disease for Nick. But in this tough disease, myelofibrosis, it can be controlled for a long period of time but it does change as the medications really don’t work forever. And sometimes it is necessary to go to transplant and we treat patients up to the transplant with Jakafi to maintain the benefit that might still be there.

After the transplant it’s not necessary anymore, of course. But that is one of the experiences that people need to understand that there is a potential for medications to control the disease, either through clinical studies and the first option may not work, the second may not work and there are always – and we try to have those here – multiple other options through conventional medications or through investigation medications to help patients. And if the transplant is necessary, we will do it when the time comes and it is a personal decision most of the time.

It’s not really one number; it has to be between the physician and the patient.

Beth:

Absolutely, absolutely. Lindsey, I’d like to ask you the last question, and we do have a few questions from our viewers. We’re talking so much about clinical trials and raising awareness, how do we do that, and how does raising awareness affect the clinical trials? I know like barely anything about clinical trials.

Lindsey:

Sure, that’s a great question. In fact, one of the things that we try to do at the MPN Research Foundation is to let people know about clinical trials that are going on so that to the extent that someone is looking for something better, kind of like Andrea was or has been. Maybe they haven’t been made aware by their own doctor of an ongoing clinical trial.

And by using our social media and our website, etc., we can make people aware of that. I think that’s – it’s a great way for people who are patients but also I think that it’s important for patients to understand the message that Andrea delivered that I think was so eloquent. Which is unfortunately, drugs don’t come onto the market without brave patients like Andrea and Nick who are willing to put themselves out there and take something that is yet to be approved by the FDA. Because the FDA has very specific standards and they scrutinize the trials very carefully. But at the end of the day, we need patients to volunteer for these trials.

I think it’s wonderful when patients do that, and it’s even better when the results are great, obviously. But I think from an educational standpoint, we as an organization and I know others try and help people to understand what their options are, what the process of a trial is. We’ve actually in the past put together graphics to help people understand how trials progress. We actually have been involved ourselves in discussions with the FDA on how trials can be more focused on the patient experience.

So I think that things are definitely going to improve, and hopefully we’ll see more drugs that are available for patients that will provide more relief very soon.

Beth:

That’s very encouraging. I absolutely agree with both of you how people like Nick and Andrea, and could be myself as well one day in the future; we can’t move forward. We don’t want to be stuck and not be able to have those results. I’m going to shift gears a little bit. We’re ready to take a question. Dr. Verstovsek, this question I believe is geared for you, and I’m going to go ahead and read it. Dolf from Holland is watching.

How is research internationally organized? Dolf goes on to say lots of trials with MPN hematologist around the world, and we can find them on clinicaltrials.gov. But is there also some specific research in some countries that’s not registered at that site? Is that something you can address?

Dr. Verstovsek:

That’s a very good question. There is an attempt by clinicaltrials.gov, which is actually the federal site, to collect all the clinical trials that are being conducted not just in MPN, obviously, but in any other condition. And the effort is really significant with the prospect of utilizing that for patients as well to identify the sources, if not only for the physicians. It is really the professional side but the patients can search that as well. Perhaps it’s too cumbersome sometimes to find information, but underlying the attempt is very well received at least in the professional circles.

If there are any other studies in other countries that are not registered, of course it’s a possibility this is the Federal Government of the United States. I am not aware, didn’t really look into that, whether other governments in Europe – and I would say some they do, maintain something similar for their own countries like in Germany or France.

This is, after all, one of the best sources of information, clinicaltrials.gov, for clinical studies.

Beth:

Great, thank you so much. We’re going to take one more question; unfortunately we’re almost out of time. But we have another event coming up October 7, and we will definitely answer many of these questions that have come through tonight. And in fact, Dr. Verstovsek will be on that panel as well, on the upcoming one. I do have another question for you, Dr. V. It’s from Julie. Do you have any tips for patients to educate their primary care provider about MPNs? And she said more specifically, PV.

Dr. Verstovsek:

The information that is available to the patients through the MPN Educational Foundation or through the information that can be gathered from the academic websites for the patients typically is organized very well for anybody to understand it.

I have patients that are engaged with us together, as we said, in that educational effort for all participants to be at the same level. That means not just us in a referral center or patients, but also referring doctors. So the best information to a primary care doctor, and I assume that was what the question was about, the local oncologist; that is delivered by us as experts in MPN and by the patients.

By bringing that information to the attention to a local doctor is valuable. There is rarely any doctor that would not appreciate so much the involvement of the patients on the part of education, and bringing the new information to the doctor. Look, the local hematologists and oncologists, that’s a hero for me.

That doctor, a female or a male, has to take care of not just the PV; it has to take care of patients in brain cancer and kidney cancer and lung cancer; both of the perspective of life and professional commitment in front of you for that particular doctor. That is the doctor that is doing all of this at the same time, and has to catch up. So we have to also realize that it’s really difficult to follow all the updates and all new developments in the field for PV or any other MPN. So, I know that doctors appreciate when the patient is engaged and brings information to them.

Beth:

Excellent advice. Julie, when you asked about their primary care providers as well, I’m sure Dr. V. feels the same way; we can take a look at Andrew Schorr and his wife Esther who created and head up Patient Power. Esther is very vocal about being a very educated care provider.

And through everything we’ve talked about today with myMPN registry or the MPN Research Foundation, or all the things that Dr. Verstovsek brought up about how he educates his patients, the primary care providers definitely should be in that conversation. Those things are all welcome.

Well, we are just about to wrap up. We’ve had a really great discussion here today, and I would like to get some final thoughts before we say goodbye. We are a little pressed for time. Nick, if you can give us a few quick, final thoughts and we’ll just go around after that.

Nick:

Well first, Beth, great job on the hosting. It was very impressive, and glad to be able to participate. And certainly want to thank all the panelists to try to keep moving folks forward. And hopefully some day the people behind us won’t have to worry about the same issues we’re dealing with today. And appreciate Dr. V. taking the time especially, and all the great work that his team is doing, too. So, wish everybody the very best, and thanks, and great job, Beth.

Beth:

Thank you, Nick, and right back at you; it’s been a pleasure having you. Andrea, some final thoughts from you?

Andrea:

Yes, thank you everyone for participating, it’s been great. It’s my first time. I would like to say that one thing I found successful was to print some pamphlets up and to distribute to my doctor and leave them out so people are aware of our meetings. And also, to really encourage people to look very seriously into clinical trials and going to an institution like MD Anderson that specializes in their disease so that they can get the best care and educate themselves the best.

Beth:

Thank you, Andrea. Those are great words of wisdom and we appreciate all of your feedback, having been in this journey for almost 20 years. Lindsey, can you give us a few final thoughts?

Lindsey:

Sure. Thank you very much for including me in this conversation; it’s been wonderful to join Dr. Verstovsek and Andrea and Nick.

I encourage anyone who has not yet visited myMPN to please visit us at www.mympn.org. If you have any concerns or questions, please don’t hesitate to reach out to me. I encourage everyone, like Andrea said, to try and get involved in your care, whether that’s through myMPN, through joining a clinical trial, and certainly just being an advocate for your own health and going to go visit those doctors armed with the information that you can.

Beth:

Thank you. Great words of wisdom. And again, we are very excited about the myMPN registry, so thank you for sharing that today. Dr. Verstovsek, we appreciate you being here. Some final words that you can give to our audience?

Dr. Verstovsek:

I really appreciate you having me on the panel; it was a wonderful experience.

And certainly what we have achieved together, I’m sure for many patients is to engage, engage and be educated, learn about what you have, learn about the abilities to help you if you are not already. Be an active participant because these conditions are there to stay with you; we don’t have a cure yet. We are working toward it. But life can be good, life can be controlled well. We have means and we are trying to do our best. So be an active participant with the local doctor, with expert. Make the most out of it and if you need a second opinion, search for it. Basically, do not give up. Be your own advocate, if you like.

Beth:

Wonderful, and I couldn’t agree with you more. It’s just very inspirational and those words will resonate with many of our viewers, I know.

Thank you, I’ve enjoyed speaking with such experts on this panel today, and thank you for the words of wisdom and best of good luck and health to all of our viewers, and Nick and Andrea. Thank you.

Living Well with MPNs – Are There New or Emerging Treatments That Could Be Right For Me?

Understanding Treatments for MPNs: Are There New or Emerging Treatments That Could Be Right For Me?

Understanding Treatments for MPNs: Are There New or Emerging Treatments That Could Be Right For Me? from Patient Empowerment Network on Vimeo.

What new treatments are in development for myeloproliferative neoplasms (MPNs)? What are the considerations when choosing a treatment plan? In this LIVE webinar, Dr. Bart Scott from Seattle Cancer Care Alliance and Dr. David Snyder from City of Hope will help viewers to understand the various treatment options for those living with polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF).


Transcript:

Beth Probert:

Hello and welcome to our Patient Power webinar today. Our topic is “Understanding Treatments for MPNs; are there new or emerging treatments that could be right for me?”

I’m Beth Probert, and I’m coming to you from Oxnard, California which is just northwest of Los Angeles. I am a polycythemia vera patient and patient advocate. I was diagnosed in April, 2016 by my specialist at the University of Southern California Norris Cancer Center. I was treated with Pegasys, which is pegylated interferon and a few phlebotomies for about 12 months. And I am happy to say that I am in remission.

But like many of our patients and caregivers in the Patient Power community, I am very concerned about the future of my condition and very interested to hear today about some of these new and emerging treatments and clinical trials that will give us hope for our future and for all of is in the MPN community.

Before I introduce our panel today, I do want to remind everyone that you can submit your questions and we will try to address every question in today’s show. If we don’t get to it, we certainly will address those questions in future webinars. You can submit those questions to MPN@Patientpower.info.

All right, I’d like to introduce our panel today. Joining us today from Seattle we have Dr. Bart Scott. Dr. Scott is a medical oncologist at the Seattle Cancer Care Alliance and a research associate in the Clinical Research Division at Fred Hutchinson Cancer Research Center. Thank you so much for joining us today, Dr. Scott.

Dr. Scott:

Thank you for having me. Hello, everyone.

Beth Probert:

Great. And I’d like to introduce our other doctor on the panel today, Dr. David Snyder. He is joining us from Duarte, California which is in Los Angeles County. Dr. Snyder is an Associate Chair in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope. Dr. Snyder, I hope I said that correctly. Welcome.

Dr. Snyder:

Thank you, I’m happy to be here.

Beth Probert:

Thank you. Now I’d like to introduce you to our patient panelist. Today we have James from Lubbock, Texas and James was diagnosed quite a few nears ago with the central thrombocythemia. James, welcome to our show today.

James:

Hello and thank you.

Beth Probert:

James, I’d like to start with you. How long ago were you diagnosed with ET?

James:

In October of 1994, I was 47 years old. I had a heart attack. If it had not been Monday morning and I was in the hospital visiting my mother, I would be dead. I had a blockage right at the aorta. But they pulled me out of it.

I’ve been active all my life. Even back then, I was running more than I do now. It just happened to me, and so eventually we got around to essential thrombocythemia, whatever that meant.

Beth Probert:

Well James, that’s such an interesting story because you’ve been dealing with this for several years. And in 1994, if I’m correct, we didn’t really have too much internet access. How did you and your family deal with this? How did you get information and educate yourself?

James:

Well, just so you know, I’m 545 miles from Houston, 325 miles from Dallas, in a town of 250,000. But luckily, we have a medical school. And so I went to the library at the medical school and I befriended one of the librarians whose husband was an oncologist, or is, and she was very helpful in trying to guide me. But back then, there really was very little information.

It wasn’t current. It was from the polycythemia vera study group, and that’s real old data and things like that. But when the internet came on, I started playing around on Yahoo, came across MPN – or back then it was MPD – Digest, and read that franticly every night.

Beth Probert:

I can certainly imagine what a revelation that was to all of a sudden have information at your fingertips. If I’m not mistaken, when we were speaking earlier you mentioned that you also through the years have attended conferences. Can you speak a little bit about that?

James:

Yes, it’s literally empowering to go – and my first one was in 1999, but to go into a room and find other people who are dealing with some kind of MPN. I was like wow; I really am not quite so alone. And over the years the quality of the information has increased tremendously, as it has in the whole field.

It’s still empowering. I have friends I’ve made by going to the Scottsdale conferences; you just learn a lot. It’s just good.

Beth Probert:

That’s very inspirational. I kind of want to shift gears a little bit here and ask you a couple questions. Do you see a specialist?

James:

I see a hematologist/oncologist in Lubbock and I have right from the start. He started me on hydrea and soon to be 23 years, I’m still on it. I’ve varied my dosages from time to time, but I’ve seen no need to see what you would consider an MPN specialist. While hydrea is working, I’m goin to stick with it and when it doesn’t, I’ll start looking around and doing other things. There’s no one I would consider an MPN specialist in Lubbock. I’ve talked to some oncologists and I had to alert them about anagrelide. I would say they don’t quite understand Pegasys versus the normal interferon and things like that.

But that’s really kind of been immaterial to me so far because hydrea is working.

Beth Probert:

And you do have that challenge of being a little bit more remote, and I can certainly see how that makes a difference. I want to ask you one last question. You’ve been on hydrea a very long time. Do you have any side effects?

James:

None really. My wife says I’m just not quite as wired as I used to be. But the things I read about, the possibilities that could be occurring, I don’t have to. I don’t know why; I just don’t.

Beth Probert:

That is fabulous news.

James:

As a matter of fact, the doctors don’t know why either. They’d like to know; I would too.

Beth Probert:

Sometimes there’s just no explanation. James, I really appreciate getting to understand your story and we’re certainly going to come back to you and learn a little bit more about your journey. I’d like to go over to our doctor panel now.

I’m going to start off with Dr. Scott. We’ve heard a little bit about James’ story, and for our viewers could you explain a bit about ET; just help us understand really what it is and more importantly, what are we treating it with and what are the goals of treatment for ET?

Dr. Scott:

ET stands for central thrombocytosis or essential thrombocythemia, so it’s been called both of those names but the principle issue is overproduction of platelets. When you see the blood counts of the patient with essential thrombocytosis, their platelet counts are elevated. There can be a wide range of how elevated we’re talking about; it could be anywhere from 650 to even greater than 2 million.

When you have a platelet count that’s really high, like above a million, paradoxically there’s an increased risk of bleeding. That’s because the platelets have, on their cell surface, what’s called a von Willebrand factor cleaning protein. It actually cleans a portion of the blood that helps in clotting. So even though they have all of these platelets, and we associate platelets with preventing bleeding and bruising; when the platelets are extremely high like that, patients can have bleeding like nose bleeding, gum bleeding.

But the real problem with essential thrombocytosis is clotting. The No. 1 cause of death in people with ET is due to blood clots. And so James was just saying, he presented with this basically heart attack that he probably wouldn’t have survived if he hadn’t been in the hospital already. That can be a common presentation that you see with essential thrombocytosis blood clots.

So the reason to treat patients with essential thrombocytosis when they are treated is to lower their risk for blood clots; to lower the risk for thrombosis. The standard therapy for ET would be aspirin, a baby aspirin a day, and then you look at different types of risk factors to determine whether or not they need cytoreductive therapy. Cytoreductive therapy is basically given to lower the blood counts.

The risk factors that we would look at age, would be history of prior thrombosis, also white count is another risk factor that’s come out recently that can predispose people for risk of blood counts. But there is a prediction model; it’s called an IPSET prediction model and it’s an international prognostic model to determine the risk of thrombosis in patients with ET. You can look at that and you can see what risk factors this patient has.

Interestingly, JAK2 mutations, so having ET with a JAK2 mutation is another risk factor for thrombosis. But if they are high risk for thrombosis, either due to age or history of thrombosis, other risk factors like cardiovascular risk factors or due to the IPSET model, these are patients that are treated with cytoreductive therapy. There are many choices for cytoreductive therapy and two of them have already – actually, three of them have already mentioned.

That would be hydroxyurea, which is a common agenda that is used; another choice would be pegylated interferon or Pegasys; and then another choice would be anagrelide. There have been two randomized trials that I’m aware of comparing hydroxyurea to anagrelide. One showed a benefit with hydroxyurea over anagrelide; the other one was basically equivalent. But for me, my preference is hydrea unless they are a younger patient.

And in those patients I typically prefer Pegasys. I think there’s more data that’s needed to determine whether hydroxyurea or Pegasys would be the best first choice. There is a randomized trial that either has completed accrual or will soon complete accrual where they compared hydroxyurea to pegylated interferon; it’s frontline cytoreductive therapy for people with PV and ET. That will help us to answer the question which is better between hydroxyurea or pegylated interferon. But both of those would be choices for initial cytoreductive therapy.

Recently one of the big things that we’ve learned about with all myleoproliferative neoplasms is the underlying driver mutations. All of the myeloproliferative neoplasms share in common up regulation of the JAK-STAT pathway. And the same thing of course is true with ET.

And so there are three common mutations seen in ET: JAK2V617F would be the most common, and then calreticulin and then what’s called the MPL mutation. So you would test your patients for those mutations if you suspect a myeloproliferative neoplasm. They’re helpful not only from the standpoint of diagnosis but also prognosis. In regards to what’s coming out in the future, there’s a lot of understanding of other things that determine risks.

So as James was mentioning, he’s done well for such a long period of time. And then there are other patients who have more rapid progression to myelofibrosis, for instance, with a diagnosis of ET. We are looking at that and we’re starting to understand more about why that is the case. One of the things that have come out is what’s called secondary mutation that can develop in patients that potentially increases their risk of going into leukemia or myelofibrosis.

Beth Probert:

Wow, that’s been really helpful to understand. When you hear James has done so well for 23 years, the same medication, some fluctuation in his dosing, do you see that often? Do you have in your patient group; have you seen people have that same success as James? He kind of joked like nobody knows why I’m not having so many side effects and I’m doing well; what’s your take on that? Is that an anomaly or do you see that?

Dr. Scott:

We do see it, for sure and I will admit I’m what we call a tertiary referral center, which means I tend to be referred cases that are more recalcitrant that have failed other types of therapies. Among the patients that I see, I do have somewhat of a swayed pool of patients that typically have more severe presentations, more severe problems, that don’t respond as well to initial treatments and have more of a prolonged course with side effects and things like that.

But that just has to do with the nature of my referral base. But certainly among MPNs itself, there are many patients who do quite well with hydrea for many years.

Beth Probert:

Great feedback; thank you, thank you. Dr. Snyder, I want to talk to you a little bit about myelofibrosis. As I mentioned earlier, I have polycythemia vera and I do from time to time get a little concerned about progression. We’ll talk a little bit more about progression in a bit, but could you talk to us about myelofibrosis and give our viewers a summary of it, and also address the treatments and the goals of the treatments through the different therapies?

Dr. Snyder:

Sure. So we’re talking about the family of myeloproliferative neoplasms, and we started with ET; P vera of course is the other.

The third type is myelofibrosis. What we call primary myelofibrosis is patients who are diagnosed right from the beginning with myelofibrosis. But we know that both P vera and ET have the potential to transform over time to what we would call secondary myelofibrosis, meaning that they started with one condition and over time it transformed into myelofibrosis.

We see certain changes when that happens. As the name implies, there’s increased scarring, scar tissue in the bone marrow; that’s what myelofibrosis means. We tend to see decrease in some of the blood counts, particularly the hemoglobin with anemia and often the platelet count. And at the same time, often the white count is normal or it can be very elevated.

One of the clues for a patient with P vera for example, is say a patient was requiring a certain frequency of phlebotomies to maintain control of hematocrit or a certain dose of hydroxyurea and after awhile the doctor notices gee, we haven’t done phlebotomy in about five, six months and still the hematocrit hasn’t gone up.

Or, we’ve been on a certain dose of hydrea for a long time and everything has been stable, but now it looks like the hemoglobin is starting to drop. That’s the kind of clue that maybe it’s beginning to transform towards myelofibrosis and the bone marrow no longer is over producing red cells, but instead there’s a decreased production of red cells.

So along with that comes a number of other features. The spleen often enlarges around that same time and people may become aware of that enlarging organ in their abdomen. It may impact their ability to eat. There are also a variety of systemic symptoms that can occur. Sometimes we see this in patients with P vera and less so with ET/, but most commonly in patients with myelofibrosis.

Those are things like fevers, weight loss, night seats, fatigue, itching, and others. That’s kind of the clinical picture that you see when a patient either starts right off at the beginning or is progressing. So in terms of goals of therapy, there are a few issues. One, just like with the discussion about ET, patients with myelofibrosis are at increased risk for blood clotting and sometimes bleeding, as well. But our main focus is to help prevent blood clots from occurring. And so the same kind of baby aspirin is needed, is used.

In addition, there is a treatment called ruxolitinib or Jakafi is another name, that is FDA approved for treatment of patients with myelofibrosis. I’ll say that’s the only drug currently that is approved by the FDA for myelofibrosis, despite the fact that there have been many clinical trials that we may talk about with other drugs. But ruxolitinib was approved based on two main endpoints. One was a significant reduction in the size of the spleen for patients whose spleen is enlarged, with relief of symptoms from that big spleen. And second was control of some of these systemic symptoms that I mentioned. Those are the two main benefits that people can achieve.

There may be some other benefits such as gain in weight for people who have maybe lost weight. There may be some prolongation in survival; that’s a little bit of a soft call but some patients may benefit that way.

So that’s the main treatment that we think about for patients with myelofibrosis.

Beth Probert:

It sounds like from what you’ve described and of course what Dr. Scott described is the symptom burden is a big driver in how you’re going to treat patients and the symptoms are also a big indication of if it’s progressing, if it’s doing what it should be doing. You’ve both mentioned a little bit about some of the mutation. In previous programming, you’ve both talked about genetic testing. My next question is when someone is diagnosed, and I know when I was diagnosed with polycythemia vera, one of the first things that was done is that I was sent to the lab to get some genetic testing.

How important is genetic testing in both of your views? I’ll hop over to Dr. Scott real quickly. At what point are you suggesting genetic testing? Is it something you regularly do?

Dr. Scott:

Thanks for asking. So, it is part of the recommend workup now for myeloproliferative neoplasms; that all patients have this testing done. It’s important to realize that we’re talking about acquired mutations that occur in the vast majority of people. When the word “genetic testing” is thrown out, there’s this automatic misunderstanding that it means that it’s something that was inherited.

The reason why that’s important is because we don’t necessarily want to convey the false message that having a diagnosis of MPN means that your kids are going to get it, because that’s not what we’re talking about with this genetic testing.

These are acquired abnormalities in the vast majority of patients with MPN. There are very rare inherited cases of MPN that have been recorded, and in the vast majority it’s something that you acquire; it’s not something that you were born with. These mutations up regulate expression of a particular pathway in your body that’s called the JAK-STAT pathway.

There are three defied mutations to date, and they are JAK2. There are two different types; there’s the exon VC617F mutation, which most people with PV have, most people with MF have and most people with ET have. But there’s another mutation called the JAK2 exon 12, which is primarily only seen in PV.

That accounts for the small proportion of PV patients that don’t have the JAK2V617F. Those are the two mutations in JAK2. And then there’s an MPL mutation which can be seen in myelofibrosis, and in ET. Then the third mutation is what’s called the Calreticulin mutation, which is the newest one that’s been described. That’s seen in about a quarter of ET patients and about a quarter of myelofibrosis patients. Those are the three driver mutations that people acquire that’s been associated with myeloproliferative neoplasms. It is now part of the diagnostic workup for these diseases according to the revised World Health Organization criteria.

So that’s part of what we mean when we say genetic testing. That’s actually not the whole picture, because there are new types of mutations that have been described that I was talking about earlier that we believe are secondary events.

They have been associated with worst prognosis, higher risk of going into leukemia, and higher risk of going into myelofibrosis. One of those that has a negative prognosis connotation is what’s called the ASXL1 mutation. If you have that mutation, there’s data showing that these patients are at higher risk of complication like progression of myelofibrosis and like progression to leukemia.

So, I think that all patients should have mutational testing, what I’ll call mutational testing instead of genetic testing. And I think it’s important not only from the perspective of making the diagnosis but also in regards to prognosis. And honestly, it also helps a little bit with therapeutic decision-making. Because we know that ASXL1 mutations have a very bad prognosis, and that might be a patient that you would consider more aggressive interventions in, like stem cell transplant, for instance.

Beth Probert:

Thank you. Dr. Snyder, PV; we’ve talked about ET, we’ve talked about myelofibrosis and kind of flipping back to PV, when you find out that someone is positive and has a mutation, and let’s backtrack just a little bit. I realize I really didn’t delve into what PV is. Could you give our viewers a little background on PV, and then we’ll talk a little further about how the mutation plays a role with that and what we look for in that.

Dr. Snyder:

PV is polycythemia vera. It’s an over production of red blood cells. It shares the properties with its cousins, ET and myelofibrosis, the JAK-STAT pathway is over activated, usually because of the JAK2V617F mutation. So the cells in the bone marrow produce red blood cells become autonomous, if you will; they’re always turned on.

Normally the body regulates very well how many red cells are produced by the bone marrow. If the tissues in the body sense that there’s not enough oxygen coming and the message gets sent through a hormone called erythropoietin goes back to the bone marrow, stimulates more red cell production. More red cells bring more hemoglobin, brings more oxygen to the tissues and then erythropoietin production is turned off.

In P vera, that production of red blood cells becomes independent of the erythropoietin signal so those precursors are always churning out red blood cells, even though the body doesn’t need them. So the hemoglobin hematocrit can go very high, and that gets people into problems with risk of thrombosis as the main issue. Also, there are systemic symptoms that we talked about in myelofibrosis can also be seen in polycythemia vera.

So the treatment goals there are to again control the risk of thrombosis by keeping the hematocrit at a safe level, and there have been some well designed trials now showing that keeping the hematocrit under 45 percent is the desired goal. Some hematologists would even be a little more blasé about it and say well, it’s under 50 percent; that’s okay. But there are now clear data to show that you’re doing a disservice to your patient by allowing hematocrits to get over 45 percent. And frankly for women, it may even be better to shoot for 42 percent as the target.

And so the question is how do you get there, and phlebotomy is certainly the most direct mechanical way, if you will, of doing that. But cytoreduction with interferon is one option; hydroxyurea is probably the most common drug used in that setting.

 And now for the last few years, ruxolitinib is also FDA approved as a treatment for patients with polycythemia vera who have become intolerant to hydroxyurea or resistant to it.

Beth Probert:

Great. A couple of questions here, Dr. Snyder; how do you decide who gets what? For polycythemia vera, and I myself have seen this; I’m a member on so many different focus groups and such, and I see that there are people, one is getting Pegasys, one’s getting ruxolitinib, one’s getting hydrea; how do you decide who gets what?

Dr. Snyder:

The first question is does the patient need any of those drugs? We stratify patients with P vera into risk groups depending on age and the presence of other traditional cardiovascular risk factors or history of stroke.

But for a young person, say someone under 60 without risk factors, they can be maintained with baby aspirin and an occasional phlebotomy from time to time to maintain hematocrit under 45 percent. And they could go potentially for many years with that approach very comfortably.

The times that we say the cytoreduction is needed, there are a few things. One if it’s a higher risk patient, say over 60 with history of a stroke, other cardiovascular risk factors for example, or a patient who has other change sin their blood, not just the high hemoglobin but now maybe the white blood cells and the platelets are going higher, and also maybe the spleen is starting to get big. Phlebotomy is not going to help those features. That’s the time where you would start considering cytoreductive therapy.

We mentioned interferon, and Pegasys is the form of it that we now use. I do consider that more in younger patients because it’s a drug that may be harder for older patients to tolerate, so that’s the starting population. As Dr. Scott mentioned, there are trials going on to kind of compare head to head hydrea and interferon to see is one maybe better than the other. There are some suggestions that interferon may accomplish more than hydrea could in terms of some of the disease parameters. That’s not clear yet from the studies.

So that’s an option in a younger person. Hydrea really still is the main go-to drug for most patients who need cytoreduction. And then ruxolitinib, as I mentioned, it’s only FDA approved or indicated for patients who have already been on hydrea and have been either resistant to it or intolerant to that drug. So you can’t use ruxolitinib as frontline therapy.

The insurance companies won’t pay for it, and as we all know it’s a very expensive drug.

Beth Probert:

That’s a very, very common thing that we do here. We talked a few minutes ago about the mutations and doing some testing. Dr. Scott, I want to go back to you. How often do you suggest that patients have the initial genetic testing? I have found out that I’m a little unique compared to some of the other people I’ve been talking to about the frequency of genetic testing. So, how often do you suggest your patients get the genetic testing, Dr. Scott?

Dr. Scott:

I’m going to be honest with you; that’s a very difficult question to answer in a definitive way, because there’s really a lack of data to address the question that you ask.

And so, I think it’s a personal decision that I assist my patients in making in conversations with them. There are a lot of different factors that go into answering that question. So, first I’ll say that everyone should have it at diagnosis, and I think most people would agree everybody should have an extensive panel sent at diagnosis to not only include the three driver mutations, but also the associated mutational changes that can be seen like ASXL1 and EVH2.

Almost all patients now are having that done at diagnosis. In regards to how frequently, it depends on a lot of factors. One of the biggest ones would be what’s the underlying health of the patient? So, would there be a utility in knowing are things changing? One of the reasons why you would want to know that, for instance, would be maybe their disease is bad enough at this time to say okay, a transplant is warranted, but you’re going to follow the patient closely

 And if there’s new mutational changes or there are other signs or symptoms, then you might consider transplant at a later time. So when those patients are candidates for stem cell transplant, then I think one could argue that more frequent monitoring would be warranted. And so I might monitor those patients every six months to a year with mutational profiles.

I do think it should be done if there’s a change in symptomatology; if it looks like the disease is changing. So let’s say for instance you have an ET patient who’s been doing well on treatment for a long period of time, but they come in and they have low blood count now. And for the first time, they maybe need a red cell transfusion or maybe even a platelet transfusion. You’ve decreased their hydrea doses and their spleen has started to increase. You see immature cells in their blood smear. All of these are signs that maybe they’re going into myelofibrosis.

[01:09:00]                  

So if that were happening, that would be another reason that I would say okay, maybe we should do this mutational testing. So, I think it’s hard to be definitive; I think it’s an individual decision made after a consultation with the patient. And I think there’s a lack of data that we have to address your question, and that’s why you’re going to hear a lot of different opinions about when they should be done.

Beth Probert:

Absolutely. And James, I just want to go back to you for a few moments. Have you had genetic testing?

James:

I think we all had it just to be sure about the Philadelphia chromosome. And I’m JAK2 positive, but other than that, no. I would like to interject sometimes the conversation has been once we find the right treatment; you’re going to stay on it. But if you get around a lot of patients, you’ll find that this drug works great for me for three years and now, for whatever reason I’m transforming; it isn’t working. Maybe I’m not transforming but it doesn’t work. But that’s the only thing I’ve had done.

Clinical trials and CALR and MPL I’m not sure right now what I’d change about my treatment. I haven’t gotten excited about that yet. But I’m aware of them through the conferences and through the Listserv.

Beth Probert:

Very, very interesting. You’re very connected and I know that when you and I talked before and we got to know each other, that you are very connected to what is out there and still kind of figuring out what do I need; things are going well. But James, you brought up a very good point. I’d like to ask Dr. Snyder; resistance. We hear the word so often, but could you talk to our viewers a little bit about what is drug resistance and what happens at that point?

Dr. Snyder:

Usually if you’re talking about resistance, say to hydroxyurea, a patient with P vera resistant to ruxolitinib, it usually implies – often implies that there is something new that’s occurred within those abnormal cells. We were talking about mutations, and that’s probably the main mechanism for the development of resistance; that a patient had a certain profile, let’s say they had the JAK2 mutation but no other secondary mutations.

Sometimes another mutation will develop in the course of the disease, and now even though for example with ruxolitinib, you may be inhibiting the JAK2 pathway pretty effectively; if a mutation has occurred that activates another pathway inside the cell, it may be able to bypass that blockade that the ruxolitinib was establishing and now the patient clinically becomes resistant. So it’s a time to wonder what’s happening at the molecular level and should we be looking at that.

Beth Probert:

If this fits into resistance and the whole issue, and we heard earlier from Dr. Scott talking about stem cell transplantation and I know that’s something that’s your area of focus. When you see resistance happening and you’re not finding another therapy that’s working, is that when stem cell transplantation is a viable option?

Dr. Snyder:

That’s a very good question, and not an easy one to answer.

Beth Probert:

I’m on a roll!

Dr. Snyder:

That’s the biggest question, really; well there are two. Who is the right candidate for stem cell translation, and when; when is the right time? We don’t want to compromise or jeopardize good quality of life that a patient may be experiencing with their current situation.

Stem cell transplantation, yes on the one hand it is a curative treatment potentially; that’s the goal of therapy with stem cell transplantation. But on the other hand, it’s a high risk approach as well, and there are risks of early death after transplant and if not death, then significant morbidity of complications that may affect the quality of life. So we certainly don’t want to rush into that approach. That’s the nuance of when is that right time.

I’ll just step back for a minute. We haven’t talked about DIPS or DIPS Plus, which I’m sure people are familiar with. That’s the Dynamic International Prognostic Scoring System for myelofibrosis that stratifies patients into low, intermediate one, intermediate two, and high risk. It helps to predict expected survival or average survival for a large group of patients with that category.

Generally speaking, once you get to intermediate two, the average predicted survival is under five years. That is to me sort of the minimum criteria to say we should be thinking about a transplant. But it’s not sufficient, because many people may be in intermediate two or even high risk and still have good quality of life. So I look for additional factors. One would be that a patient starts increasingly requiring red cell transfusion because of severe anemia; that’s one trigger. Because that would indicate that survival may be shorter.

The other is to look at the blasts in the blood. Patients may have none, or they may have a low number, say 1 to 3 or 4 percent; that hovers in that range. And then over time, something happens and now it’s 8 to 10 or 8 to 12 percent. Again, it may be one of those mutations that’s come along.

That gives you a sense that the patient is on the way towards transformation, so that’s another trigger to say this is the time to think about a transplant.

Beth Probert:

So definitely not a decision that is taken lightly; it is sort of a last sort of therapy, so to speak, a strategy to take because of the serious effects it could have on the quality of life, if I understand you correctly?

Dr. Snyder:

Again, in a sense it is. I like to say that I don’t like to take patients too early, nor too late to transplant. Because we want patients who are potentially going to benefit from it to have that chance. So too early means that a patient is doing well in their current therapy, they have a good quality of life, they’re doing the things that they need to do, that they want to do; we don’t want to interfere. Too late, that’s a relevant term because it’s hard to say that it’s ever absolutely too late.

But someone who’s transformed to leukemia, that’s a much more difficult situation. It’s not that we can’t transplant a patient in that situation; you need to go through treatments first to get the leukemia back into the more chronic stage. It complicates the whole picture; outcomes are not quite as good.

The other besides leukemia is the general organ function of patients as they get older and they have other issues. Their heart function, their kidneys, their liver, their lungs; those need to be in pretty good shape to be able to withstand the impact of a transplant.

Beth Probert:

So it’s a very intricate decision making process and highly specific, is what I hear you’re saying.

Dr. Snyder:

It is. I’d just like to get back a minute to what we’ve been talking about mutations.

As we’re learning more about what secondary mutations can be found and what their clinical impact is, they’re being incorporated into prognostic scoring systems so not just DIPSS, but there are things like MIPSS, molecular scoring.

So, incorporating those data along with the clinical parameters. We’re not ready yet, but there may be a time where we can define a patient’s risk through the genetic profile and allow us to say okay, this patient, even though clinically they’re doing well, we know that their risk for not doing well in the short term is X or it’s a much shorter timeframe, and we better not wait – or it would be better not to wait – to move to transplant since we had said that this patient is a candidate and they have a donor.

So we’re not going to wait and risk the chance that they would lose the benefit. We’re not there yet, but I think that’s the direction we’re hoping to head to in the coming years.

Beth Probert:

That’s great to hear about where we’re going with this; what we can expect in the coming years. It sounds like it’s going to get highly specific and very useful. Now I’d like to take the time to talk about some clinical trials. Dr. Scott, I’d like to have you start off with us. What’s new and promising? If you could talk about a few clinical trials that maybe are going on at SCCA, or that you’d like to share with us and then Dr. Snyder, we’ll go back to you and you can give us your feedback. So Dr. Scott, can you lead us into that subject?

Dr. Scott:

Sure. We have a trial with a drug called imetelstat for patients with myelofibrosis. The accrual is currently on hold. A single center phase II result was published in the New England Journal of Medicine showing there were some patients who were able to retain a remissionof their myelofibrosis with treatment with imetelstat.

This includes both molecular remission and morphologic remission. Molecular remission would mean that their abnormal mutations went away and it responded, and morphologic remission would mean that visually the fibrosis had improved significantly. The phase II trial is currently on hold and they’re evaluating data. I’m helpful that the drug will continue to be explored in clinical settings. It does have a novel mechanism of action; it’s what’s called a telomerase inhibitor.

As I said, the drug is known as imetelstat. There are many centers that were participating in that phase II study. We just opened a trial with pactritinib. Pactritinib is also a JAK inhibitor, and actually I think it’s probably better to call these drugs JAK-STAT pathway inhibitors, because not all of them actually work directly on the JAK receptor, so I think that’s important to know.

These basically inhibit the JAK-STAT signally cascade. This drug, pactritinib, is in clinical testing. It is not yet FDA approved. It’s somewhat similar to ruxolitinib but it does appear to cause less cytopenias, so less toxicities with lowering of the blood count. It could be potentially useful in patients with low platelets. That’s one of the chief toxicities that can be seen with ruxolitinib are Jakafi is lowering of the platelet counts.

So, I’m hopefully that this drug will be approved in the near future. It was put on hold for the FDA for a brief period of time, but as I said the drug is now being studied again in a phase II trial, looking at different dosings. There are many centers participating in that study.

And then we also have a transplant study that’s looking at giving JAK inhibitors before transplant in an effort to improve the overall condition of patients before they go into transplant.

This is specifically for myelofibrosis patients. Patients with myelofibrosis can have a higher treatment-related mortality with transplantation because of other things that are going on with their body like malnutrition, the fact that they have a very big spleen, and other factors such as organ involvement with fibrosis can lead to a higher treatment-related mortality. They also have a slightly higher risk of graft failure in comparison to patients with other types of myeloid malignancies.

So, we’re hopeful that giving a JAK inhibitor before transplant can help improve the post transplant outcomes. So those are the three major trials that we currently have open. Of course there are other centers with really exciting drugs in development, as well.

Beth Probert:

Wow, that sounds very exciting. I know that I can say just hearing that there’s such a focus with MPNs and these trials.

And Dr. Snyder, what is going on in your neck of the woods at City of Hope and other trials that you’d like to tell us about?

Dr. Snyder:

Yes, we have a number of trials. We have the pacritinib and the imetelstat trial as well. We have two other trials that are for patients who have failed or progressed on ruxolitinib that have totally different mechanisms of action sort of outside of the pathways we’re talking about. One is called SL401, Stem Line 401. It’s an interesting sort of an immuno toxin; it’s a dual functional molecule that has an IL3, interleukin 3 portion that’s linked to a diphtheria toxin. It’s somewhat like a Trojan horse type of thing.

The cells in myelofibrosis and other hematological malignancies have an interleukin 3 receptor on their surface, and this IL3 molecule will bind to that interleukin receptor. That complex is taken inside the cells and then the diphtheria toxin is released and is able to kill the cell from the inside. So that’s one mechanism.

There’s another approach; there’s a molecule called CD47 which has been referred to as the “don’t eat me” signal. So, macrophages which are big cells in the body and in the blood and tissues, their name means big eaters. They like to eat foreign cells, tumor cells, bacteria, etc.

But some of the tumor cells or the malignancies become very clever and they have this protein called CD47 on their surface that sends a signal to the macrophage: don’t eat me, stay away and helps the cells to survive. So there is an antibody against the CD47 that binds to the CD47 and interrupts that pathway and then allows the macrophages to do their jobs, which is to eat these abnormal cells.

So that’s another approach that’s being tested not just in myelofibrosis but in other conditions as well. There is some data, sort of preclinical, that this approach may actually reverse fibrosis in some models, so it’s kind of intriguing particularly for patients with myelofibrosis.

The thing I will mention, we know that ruxolitinib is the only FDA approved drug so far; there have been several others unfortunately that have gotten just so far and then because of toxicities have been taken off of the table. But to me, I think another approach is combination therapy that is taking ruxolitinib as the base and then combining it with the second drug that has a totally different mechanism of action, and the two of them then perhaps can synergize and kill off the cells.

Those are trials, a quite a few of them going on around the country and I think those have a lot of promise.

Beth Probert:

And when you mention combination therapy, you both have mentioned it; are we looking at more of a personalized medicine? What’s your feeling on that, Dr. Snyder? Is it at that point we’re getting more personalized and we’re looking at that one person and saying this is going to work more specifically for you?

Dr. Snyder:

I think that’s a very good point, and I think as we learn more about mechanisms of action of some of these drugs and we talk about targeted therapy, it is something that can be very individualized potentially.

We talked about the genetic profile of what mutation someone might have. And so there may be a second drug beyond ruxolitinib that targets one of these secondary mutations that a patient might have. And so for that person with that particular combination of mutations, ruxolitinib plus this second targeted therapy may be just the right thing for them.

Even a drug like imetelstat, at least on data based on small numbers from Dr. Tefferi’s work suggested that there may be a mutational profile that defines the best responder type of patient, and conversely, patients who are unlikely to respond at all to that drug. That would be terrific to be able to say okay, don’t waste your time with this drug for this patient, but go in this direction because this is much more likely to be effective.

Beth Probert:

It could be life saving; it could get to the result much quicker than going through another therapy that just is not going to do it.

Dr. Snyder:

For sure.

Beth Probert:

Very interesting. So, quick question for you James, before we move one. We’ve talked about a little bit about clinical trials. James, have you considered a clinical trial? Or you’ve been stable; would you consider one in the future if your condition changed?

James:

Very definitely. But you know one thing we haven’t touched on and what drives the doctors crazy, probably, is the psychology of the diagnosis. We as patients quite often tend to think if I just took thing X or had therapy Y, I would be okay. And as these doctors know, it’s not that simple. But yeah, if I thought I would benefit from it and I needed to, of course.

Beth Probert:

You bring up an excellence point, James, because it is the psychology behind really how we… you’ve been doing this for 23 years and you obviously have educated yourself which helps you to understand what’s going on, which balances everything out. I know that I, as I mentioned, I’m in some support groups and I see people doing combination therapy. And it’s the old adage: he’s doing two things and I’m doing one, and I’m sure doctors don’t want to hear that.

James:

There are other patients; the last thing they want to know is anything about the technical side. Just: I’ll go to the doctor and the doctor says this, and I do that.

Beth Probert:

There is, indeed.

James:

I think even I’m on one extreme and they’re on the other.

Beth Probert:

Definitely. We have a little bit of time, and Dr. Scott, I’d like to go to you.

We have a question from Pauline, and she asks: is there any way to determine declining blood counts such as anemia and thrombocytopenias are due to drug side effects or the disease process? And she goes on to say: my husband has been on Jakafi for just over a year, and these declining cell counts began a couple of months ago. So let me know if you need to repeat that. Could you comment?

Dr. Scott:

No, I’ve got it. There are things that are helpful to distinguish between drug toxicity and to these progressions, and one is timing. The cytopenias that are experienced with ruxolitinib, as long as the dose has remained the same are usually early side effects. So, most of the cytopenias are during the first eight weeks of therapy. So if you see early cytopenias, it’s more likely to be a drug effect. If you see later cytopenias, it makes you more concerned about disease progression. And to know definitively of course, you could repeat a marrow aspirate or a biopsy and that can be helpful.

[01:30:00]

And then other co-associated symptoms or size like increasing spleen size, or return of puritis can all be signs that the ruxolitinib is no longer working. But as I said, the side effects of drug-related are usually early events within the first eight weeks when treated with ruxolitinib.

Beth Probert:

Great. I think that’s going to be some good feedback for Pauline and some talking points that she can bring back to her specialist. We are coming to a close, and what I’d like to do now is ask each of our panelists just for some final thoughts or comments. You know, I’m feeling very optimistic from this discussion this evening to know that there’s just constant thought on these rare diseases, and there are clinical trials and research. But Dr. Snyder, let me start with you and if you could just give us some thoughts you’d like to share with us that you think would be meaningful?

Dr. Scott:

Sure. These are obviously difficult diseases because they’re hard to cure. But I will focus first on the role of stem cell transplantation as the only current only curative approach. We are trying to improve both the efficacy and the safety of that approach, and Dr. Scott mentioned studying the role of JAK2 inhibitors in the peritransplant time, for example, as one. It turns out that ruxolitinib also is an effective drug to treat one of the main complications, which is graft versus host disease. We have a trial actually looking at it as a prophylactic way to prevent graft versus host disease.

So just to say that there’s a lot of work being done on that front to try to improve outcome for patients with the transplant approach. But of course we’d all love to have – we all think about CML, that was mentioned; the Philadelphia chromosome. The Gleevec story is kind of the model that we wish we could duplicate with many of the diseases that we treat, recognizing at the same time that it’s very unlikely.

Because in a way, patients and doctors were lucky with CML because it’s a very simple biology. And if you come up with a drug like Gleevec that targets really the definitive driver of that disease, you can have dramatic clinical benefit.

Not quite the case with the myeloproliferative neoplasms; more complicated. Ruxolitinib, we all hoped this is going to target the JAK-STAT pathway; it’s going to shut it down and restore normal hematopoiesisIt’s not quite that simple.

But we certainly have hope and optimism that with many of these trials that are going on, particularly as I said clinical trials with combination therapy, that that is going to get us closer to that point. I’m a transplanter but I would love to be put out of business because we have drugs or a drug that is so effective, transplant is just a thing of the past. Hopefully, one day that will be the case.

Beth Probert:

Wow, and that is very powerful. I will always remember those words; that’s really great. Dr. Scott, can you give us some final thoughts on just anything to let us know again what we should be looking for, what’s in the future, some optimism; whatever you feel is meaningful?

Dr. Scott:

I think there is a lot of hope. When you compare what we know about myeloproliferative neoplasms now with what we knew about them six years ago, it is really remarkable. It was in 2005 that the first publications were published about JAK2, and we began our understanding of the underlying mechanisms of myeloproliferative neoplasms.

And over those 11 years there have been a lot of advances. So, I’m very encouraged by not only the clinical trial work that has been done, but also the basic science and the expansion of our understanding of these diseases. So when you compare what we have now with what we had ten years ago, it is really remarkable. I also do transplants but I do non transplant as well and I hope to be driven out of business. I would be okay with that.

Beth Probert:

That’s wonderful to hear; again very optimistic. James, you and I were chatting a little bit before our show started. James was commenting how even from 2014 to 2017, that there have been so many changes in progression and therapies. And James, I’ve got to say you’re like an MPN warrior.

You’ve been dealing with this for 23 years, you’ve been not only optimistic; you’ve been so resourceful, you are a born researcher. I would love to turn the stage over to you right now. And if you could give us some of your thoughts, some things you’d like us to know and help us feel more optimistic as we go forward.

James:

Well, I’m very optimistic; I mean it’s just amazing compared to 1994. Actually, I was one of the data points in some of those 2005 studies. But there’s the MPN Research Foundation – let me throw in a plug for them, patients; they have funded some really specific studies. If you can’t go to conferences nearby or Scottsdale or New York – Dr. Silver runs one in New York; I know they’re in Seattle and all over now, get involved in a focus group. I drive to Dallas just to be around a focus group of those people. It’s tremendously empowering to talk to other people. Because your friends are like, you don’t really have a problem; you don’t look sick or anything, you know?

Beth Probert:

That is something that MPN patients hear quite a lot. But go ahead, James.

James:

I’m just excited. When I have to get more knowledgeable and detailed about these things, I will but I’m not there yet. My goal is like the physicians here; I intend to die of something else. It didn’t get me the first time; I’m planning on no second time.

Beth Probert:

I think that is wonderful. You know, I would like to say that optimism is what is going to get us through this condition. I don’t tell too many people because I’m very optimistic, but I do agree with you James; I really connect well with people in focus groups. I drive sometimes about two hours each way into Los Angeles to see my specialist because that’s of value to me. If I ever could give advice, it would be make sure you’re connecting well with your specialist.

And that they are, like Dr. Scott and Dr. Snyder, very well versed in their field and in their clinical trials and things like that. So, wrapping up, a big thank you to our panel; I really believe that this webinar this evening gave us a great deal of information. Dr. Scott, Dr. Snyder, you both have very busy schedules so appreciate it. And James, you too took time out tonight so thank you all.

We have an upcoming webinar I’d just like to talk about really quickly on September 20th, and it’s what you can do to advance MPN research so I hope everyone will join us then. We will also be showing this video again and again. So thank you for our panel and thank you all for taking the time to watch Patient Power. Good night.

Living Well with MPNs – What You Should Know About Genetic Mutations

What You Should Know About Genetic Mutations

Living Well With MPNs: What You Should Know About Genetic Mutations from Patient Empowerment Network on Vimeo.

Should you get a genetic test? JAK2, MPL, CALR, ASXL1: Mutations associated with myeloproliferative neoplasms (MPNs) can bring up lots of questions. What do they mean, and how do they impact your disease? The goal of this webinar, featuring Dr. Alison Moliterno from Johns Hopkins School of Medicine and Dr. Stephen Oh from Washington University School of Medicine, is to help patients understand genetic mutations.


Transcript:

Andrew Schorr: Hello and welcome to this Patient Empowerment Network program, produced by Patient Power. I’m Andrew Schorr joining you from Carlsbad, California. Over the next hour we’re going to talk about something that’s very personal to me and probably to you, and that is the whole idea of genetics related to living with an MPN. What does it mean? Does it change over time? What is your version of an MPN? What does it mean for prognosis? What does it mean for treatment? What does it mean for clinical trials opportunities? So we’re going to be discussing all of that.

I want to thank our sponsor, Incyte Corporation for supporting this educational activity. We’re going to cover the country and we invite your questions as we go along. Send them to MPN@patientpower.info. Many of you have. And remember if you have to bow out at some point, the replay will be available and we’ll have video clips. So we’ll reach literally a few thousand people living with MPN worldwide, and we’re happy to do that.

Let’s get started. First I want to introduce you to one of our medical experts who’s joining us. He’s been on programs before. He joins us from Washington University and the Siteman Cancer Center in St. Louis; that’s Dr. Stephen Oh, who is an MPN expert there. Dr. Oh, thank you so much for joining us.

Dr. Stephen Oh: Hi, Andrew. Thanks for having me.

Andrew Schorr: Thank you, Stephen. Okay, let’s go from St. Louis to Baltimore, Maryland and the Johns Hopkins University Medical Center and another expert in MPNs who’s been with us before, and that is Dr. Alison Moliterno. Dr. Moliterno, thank you so much for being with us today.

Dr. Alison Moliterno: Thank you, Andrew. Thank you for having me.

Andrew Schorr: Sure, pleasure. We’ve got a lot to cover. And then also I want to welcome back one of the members of our community, someone who was diagnosed many years ago, a couple of decades ago with ET, and then a year ago it became myelofibrosis. She’s a preschool teacher in Peoria, Illinois. She’s been with us on our programs before; Marsha Krone. Marsha, thank you for being with us once again.

Marsha: Thank you. Hi, Andrew.

Andrew Schorr: Marsha, let’s visit for a minute. I was diagnosed in 2011 and then eventually had a genetic test which came up with a bunch of results. One of them for me, if I get it right, JAK2V617F.

I had no idea what that was, and then a couple of other genes that to me seemed kind of like alphabet soup. And I had one of the peers of these experts here, Katrina Jamison. We went over it and she said I think it’s the JAK that’s kind of driving things. We’re going to talk about what are the driver genes, and what may not be, or what do we know at this point. Marsha, you had a genetic test, too. What did it say?

Marsha: My genetic test came out as Calreticulin type 2.

Andrew Schorr: Okay, so we’re going to figure out what that means. Dr. Oh, let’s start this way. People think genetics. I know genetics maybe had something to do with being bald, and I see you have a similar hairline; or dark hair, or brown eyes, or whatever. Hereditary genes; are we talking about that or are we talking about something different?

Dr. Stephen Oh: That’s a basic question that comes up with almost every new patient that I see.

The short answer is that when we’re talking about genetics with relation to the MPNs, we’re not talking about those kind of things that you’re born with that may affect your hairline and whatnot. These are genetic mutations that are acquired over time that you’re not born with; they’re not passed down to your children or your relatives, etc. So that is a very important distinction that I try to make clear with every new patient that I see.

Andrew Schorr: Okay, and one follow up question to you. People say okay, Doc, what gave me this genetic injury, if you will, to lead to these illnesses? Do we know?

Dr. Stephen Oh: That’s another question I cover with almost every new patient; that I think for that one I guess the answer is a little less satisfying. My answer is that for the most part it’s random chance.

What I mean by that is that we know particularly from research that’s come out n the last five or so years that all of us acquire mutations randomly over time as we age. But fortunately for most individuals, those mutations land in spots where they really have little to no consequence. But for those that, for instance, acquire the JAK2V617F mutation or acquire a Calreticulin mutation, that really becomes most likely the main driver for what ultimately becomes an MPN.

Patients of course ask did I do something wrong, was I exposed to something? And while we can’t necessarily exclude that those are factors, I think for the most part it’s that just kind of randomly these mutations landed in the wrong place.

Andrew Schorr: Dr. Moliterno, we’ve mentioned a couple of these onco genes I think you call them – cancer genes, the JAK2 gene and Calreticulin type 2, I didn’t even know about that.

Can you first of all rattle off some of them just so we know the landscape of what are genes that seem to be associated with MPNs today, knowing that this will probably expand?

Dr. Alison Moliterno: I always like to tell patients a little bit about the history when these were first diagnosed because we talk about them now as if they’re common knowledge, but they are really quite recent in our understanding. We’ve known about the myeloproliferative diseases for more than 100 years, but it wasn’t until 2005 until the driver of many of the diseases was understood to be JAK2V617F. So that discovery occurred in 2005. Before the JAK2 discovery, we didn’t understand really if it was acquired mutations and what genes were involved. JAK2 is the most common of these.

If you look at 100 patients with the classical MPN, meaning PD, ET, and myelofibrosis, 75 percent overall of those individuals will have the JAK2V617F mutation. Not long after the JAK2V617F mutation there was a discovery in mutations in M-P-L or MPL. That accounts for about 5 percent of those 100 individuals with either ET or myelofibrosis and then in 2013, that was the discovery of the calreticulin mutations that comprise about 20 percent of individuals who have ET or myelofibrosis. So 2013, that’s fairly recent and those are the three drivers.

I like to say that if you could put the same mutation, the JAK2V617F or Cal or MPL mutations that we see in our patients, if you could put those, say, in a mouse; they would drive a similar disease in the mouse so that you get polycythemia vera in a mouse if you make the mouse have the V617F mutation. That’s how we’ve kind of come to understand that they drive the disease. They may not drive all aspects of it but they drive the basic process.

Andrew Schorr: I know there’s another gene that people have seen too; ASXL1. What is that one?

Dr. Alison Moliterno: In addition to these drivers we’ve also discovered a lot of genes that seem to modify the MPN or associate with certain subtypes of MPN. So for instance I said usually JAK2 MPL or CALR can all drive platelet count high and give a disease like ET. Then what happens when patients develop myelofibrosis? We find that perhaps other lesions are acquired.

Those are genes that don’t drive myeloproliferation so much but they seem to drive the way that the chromatin or the nucleus is managed; they seem to maybe set up the other aspects of MPN that associate with myelofibrosis. And ASXL1 is probably the most common additional genetic lesion or acquired mutation that occurs in individuals with myelofibrosis.

Andrew Schorr: Okay. Dr. Oh, people may be tested and we’re going to talk about who should be tested and when. How do you know what’s the driver gene? And it sounds like this continuation of identifying genes just keeps going, too.

Dr. Stephen Oh:Certainly Dr. Moliterno gave a nice circle overview of when the three primary driver mutations were discovered.

We’re sort of lucky now that in today’s day and age we kind of look at this now as standard testing. So JAK2, MPL and calreticulin so much so that many physicians including myself, we kind of go about this in an algorithmic fashion. So for instance if I have a patient with newly diagnosed myelofibrosis, I’ll start by screening for the JAK2 mutation; if that’s negative, go to Calreticulin and if that’s negative go to MPL.

And so with those three genes, the majority of patients with any of the three main MPN subtypes, whether that’s QV, ET, or myelofibrosis; they’ll be positive for one of those three. There’s a subset that’s at least on the order of 10 to 15 percent of patients with ET and myelofibrosis who will be negative for all three of those mutations, what we’re now calling the triple negative category. But the vast majority of MPN patients will have one of these three mutations which we consider the main driver of mutations.

So, in some sense again we’re sort of fortunate that it’s become almost straightforward in terms of at least the top level genetic testing for these diseases.

Andrew Schorr: So that was my question to you, Dr. Moliterno. Some people have maybe had fights with their insurance company or their doctor as related to testing. How do you view this now and how could it be positioned on how it’s really not elected, if you will, but essential to get a clear picture of an individual patient’s situation?

Dr. Alison Moliterno: This comes up in my practice and I’m sure Dr. Oh’s practice all the time, in that in the olden days before our understanding of what causes these diseases, and again the cause was these acquired mutations and in the olden days we would use histology, looking under the microscope, looking at blood counts and sort of put a name to this polycythemia vera and myelofibrosis.

But within that was such a vast variability of what the disease actually was, that that name really did not tell us too much. Now, we’ve really come to understand that what you have is defined by these molecular lesions. They’re not just of academic interest; they actually really tell us quite a bit about what you’ve got, what your prognosis is, and where it’s going. So physicians, we really can’t function and counsel patients appropriately without this knowledge. So there’s no longer elective or of interest; it’s really critical in defining what you’ve got.

Andrew Schorr: Okay, everybody. You heard it, so this is what you’re advocating for with your MPN specialists, which hopefully you have like the two with us. This is standard operating procedure; there shouldn’t be nay question with an insurance company or anybody to help you and your doctor know what you’re dealing with

But then the next question is, Dr. Oh, where are we now even in research, where things are headed so there will be treatments that line up with the different genetic situation?

Dr. Stephen Oh: I’ll start my answer to that question by going back to when the field began to develop inhibitors of JAK2 for the treatment of patients with MPNs and extrapolating from other diseases, I think there was an assumption that the patients that would respond best or if at all to JAK2 inhibitors would be those that carry the JAK2V617F mutation. What we now know quite clearly is that even those patients that do not carry the JAK2 mutation, they also tend to respond to JAK2 inhibition. So again in the case of myelofibrosis, patients who are calreticulin mutants, they also respond to JAK2 inhibitors as well.

So that’s an example where I think in a good way the use of those kinds of treatments is not limited or defined or restricted mutational profile. But otherwise in terms of the research front, identifying or defining treatments specific to different mutations, we haven’t made a lot of headway there. For instance, you can imagine now we have identified the calreticulin mutation in many patients with MPNs; can we devise a treatment specific for that? So while again on the one hand like I mentioned, it’s a good thing that those patients do respond to JAK 2 inhibitors; can we come up with something very specific to calreticulin with the patients there?

There are certainly a number of research groups that are working on that kind of question, but we currently do not have anything specific in that regard.

Andrew Schorr: Dr. Moliterno, I want to get a question from you about that because I’m sure you’re asked. Somebody says well – Marsha could come to you and say well, I’m CALR so what do you have for me? And/or you also mentioned triple negative, and I think often I’ve heard that term in breast cancer; women who were triple negative there, and say what do you have for me in that situation? So talk to us a little bit about those situations, and does it vary now with treatment approaches yet?

Dr. Alison Moliterno: I think another aspect of this is we may not today have the specifically targeted treatment but as Dr. Oh mentioned, what we’ve learned is that these three main lesions, CALR, MPL, and JAK2 all seem to over signal or work their effects through this JAK pathway.

So even though you may not have the JAK2 mutation but you have the CALR, it seems like the end result of over signaling is in the same pathway and therefore JAK inhibitors would be beneficial in individuals who have that over signaling pathway. So that’s one thing we’ve taken away; that while even though we don’t have – and that’s a good thing because that tells us that inhibiting this pathway overall will benefit the majority of individuals with these lesions, whether they’re JAK2 or CALR or MPL.

The other thing about the profiling is how much of the mutation you have. So another I think we’ve learned is that we can measure the amount of these mutations, and that’s a variable across patients and gives us quite a bit of information about – again – the type of lesion, disease you have and gives us  better information about the prognosis and why you might have a little more fibrosis than someone else.

So again, the type of lesion you have and the amount; we’re now learning to use that information. I think another thing we’ve learned is these terms triple negative, which is a term that we understand okay, that means you don’t have any of the three drivers that we know of.

But as we’re learning more about extended mutation paneling or doing different tests to look at the entire genes, we’re finding that most of those individuals really do have lesions in the JAK2 gene, or the CALR gene or MPL that maybe aren’t in the specific areas that the test was sent for. So that’s another benefit of this revolution in being able to define these lesions personally so that your disease really can be diagnosed.

Andrew Schorr: Okay Marsha, you’ve been sitting there quietly and I wonder, is this making sense to you? You’re my co-host with this; is it making sense?

Marsha: It does make sense. When I first was diagnosed, they just said you simply have ET because you have it. Then they discovered more mutations. I like to know everything about how my body is working, so I wonder how valuable it is to have additional genetic testing to see if you have other mutations that may affect prognosis?

Andrew Schorr: Right. So Stephen, and also like serial testing at some other time? She went from ET to MF over many years, so when do you test again or how does this change?

Dr. Stephen Oh: Speaking sort of broadly at first, the more extensive genetic testing which is available through numerous laboratories now, which can test for any – quite often these panels went through 20 or 40 genes; some of them hundreds or more.

The use of those in the clinic has evolved pretty rapidly over the past three, four, five years. In my own practice five years ago I was certainly not routinely recommending that kind of testing. But today, particularly with patients with myelofibrosis, I am doing it much more frequently and the question of course is as you raised; what utility does it have in terms of prognosis.

And there especially I think in myelofibrosis, is where more and more literature has come out giving us a better handle on what effect these different mutations might have on prognosis. That’s why more and more I’m beginning to recommend this kind of testing for my patients with MF.

In the case of QV and ET, it’s a little bit further behind in terms of data to indicate what these different mutations might mean, but we have also seen more literature come out, not as often but do consider that kind of testing for those patients as well. In every case it’s kind of an individualized discussion with the patient. I always start out with how much do you want to know. Marsha said I want to know everything, so that’s the kind of patient where you say alright, well, maybe let’s do this.

Others say well, I don’t really necessarily know I’m going to interpret this; it’s alphabet soup. Do I necessarily want to know what the statistics say to expect in 20 years, etc.? Again, it’s an individualized decision with every patient.

Andrew Schorr: Dr. Moliterno, there was another patient who was going to join us who couldn’t make it because she’s being scheduled for a transplant. She’s getting her life in order for that; someone with I think myelofibrosis in the Seattle area.

But she did have three mutations identified, so let’s see if this makes sense: ALX1, if I get it right, TP53 and SFB1, if those are other ones? So the fact that she has this sort of alphabet soup, does that mean that that meant you’re headed for transplant because that shows up? You know, one knows is more – more weighty, if you will.

Dr. Alison Moliterno: This is knowledge that we’re kind of pulling in as we speak, and that the meaning of more than one mutation, different types of mutations do seem to have prognostic significance.

So as we’ve learned that generally the more mutations you have, more individuals at a certain point of time generally is concerning. It means that there’s a lot going on in that stem cell and that maybe there’s some instability to allow these mutations to occur. And then it does matter which type. Some mutations seem to have more independent prognostic than others. ASXL1 tends to be one that is seemingly more associated with developing myelofibrosis. SF3B1, one of those she has, may be a less negative prognostic indicator.

But again, these are important and having three at once is a concern, and it sounds like a reasonable plan to move forward with transplant because we understand that we don’t really have a medicine that can address all of those lesions and that this is more high risk disease.

Andrew Schorr: I want to remind our audience a couple of things. One is you’re hearing how sophisticated the testing is, and then you can imagine the interpretation.

We have two noted experts. The typical hematologist is not going to see this very often. So whether you go to Washington University, I go to UC San Diego, Marsha goes to the Lurie Cancer Center, Dr. Moliterno is at Johns Hopkins. You know some of the others where you go; you want to consult with an MPN specialist. As the data comes back, what does it mean for me now or on your journey in the future.

The other point I wanted to make is of course we want to take your questions. So send them to MPN@patientpower.info and our wonderful MPN community manager, Jamie, is standing by and she’ll be forwarding these to me. Obviously, a lot of you ask very personal questions; what should I do, Dr. Moliterno, Dr. Oh; I’ve got XYZ. And that’s not fair to do that here, so that’s our disclaimer. You want to go back to your MPN specialist – it could be one of them – to discuss it.

We did get some questions in earlier. Dr. Oh, Tammy wrote in and she said can you provide more information on being PV JAK2 negative? She says I know we’re limited in number compared to other patients. It would be nice to know the basics. How much more different are we and is our treatment any different? So, JAK negative PV.

Dr. Stephen Oh: That’s a great question and it’s a challenging question. I would say that in part because we know that in the case of PV, at least 95 percent or greater of patients with bonafide PV carry the JAK2V617F mutation and it’s at least 95 percent; it may be higher than that. And even those that are negative to the JAK2V617F mutation, there’s another small group, probably less than 1 percent, who carry an alternative JAK2 mutation, an exon 12.

 So between those two, patients with PV, again the vast majority do have a mutation in JAK2. That does leave a small sliver that you could call JAK2 negative PV, and there – it’s sort of being a skeptic – the first thing I say when I’m asked to evaluate a potential case like that is am I convinced that is the correct diagnosis? Do they truly have PV versus a potentially secondary cause of erythrocytosis?

And so there, sort of again you have to rely on the old school diagnostic criteria; do they otherwise have the features of the disease? Does the bone marrow, is it consistent with the diagnosis? Are they like a classic patient in that they have a low epo level, etc. But to get to more specifically to the question, if you’re convinced that that’s the correct diagnosis, essentially I treat the patient the same way I would treat a JAK2 positive PV patient.

In other words, I would use the same kind of treatment calls in terms of a hematocrit less than 45, treat them with cytoreductive therapy and the appropriate circumstance if they’re considered high risk, if they have had a prior history of thrombosis; aspirin considered standard therapy for these patients. Again, if I do believe that is the correct diagnosis, I essentially treat them similarly to patients with JAK2 positive PV.

Andrew Schorr: Okay, and Alison, do you concur in that?

Dr. Alison Moliterno: I do. I think we have a name for the disease, polycythemia vera, where you make too many cells due to an inherent stimulus of the bone marrow. I think now in this age, we are really coming to redefine PV as the disease that has mutations in the JAK2 gene. I’m always concerned when someone has been diagnosed with JAK2 negative PV because as Dr. Oh says, maybe they have something else.

A couple circumstances that I’ve observed is that sometimes the diagnostic testing, when it was done and it was done with JAK2V617F testing that was not sensitive enough. So again we have this issue of how much of this do you have? And some PV patients can have very low levels of the JAK2 mutation that if you use an assay in a laboratory that wasn’t very sensitive and you only detected levels of 10 or 20 percent, they would be read out as negative. That’s happened in my practice a few times where patients went high and low all over the place trying to get a diagnosis; JAK2 negative. Finally when a more sophisticated or sensitive test was done, they’re positive.

The other issue is that there are other mutations aside from V617F in the JAK2 as Dr. Oh said; there’s exon 12 and then there are some others in various parts.

So when we do some of this more expanded molecular profiling, the laboratories are able to look not just at the V617F site, which is where most tests – they only tell you yes or no at that site; but they’ll look at the entire part of the coding region of the JAK2 gene. You’ll find patients who have an unusual mutation down the way that’s like – And I think it’s important because there are some people who really don’t have a myeloproliferative neoplasm; they have something else and they’ve been told for 25 years that they have PV.

And it is nice to either make that diagnosis or not. And so I think Stephen has been in that situation also, where maybe they were labeled because that was the best information we had at the time, but they really should be reevaluated.

Andrew Schorr: And I think that’s the point for our audiences. You with the best testing, with the best specialists you can get to, you want to know what you’re dealing with; what is your situation.

Here’s a question we got so Marsh, just for you. You mentioned at the beginning, Marsha, that you have CALR type 2. Can you describe that? So let’s make sense of that. There was a support group leader, Kim, who wrote in. Kim wanted to know how do CALR types 1 and 2 manifest and progress? Dr. Oh, what’s the difference between CALR1 and CALR2? What does it mean?

Dr. Stephen Oh: There are a variety of different types of mutations in the calreticulin gene, but the so-called type 1 mutations are the most common and the type 2 are the second most common; slightly different. Functionally they may have slightly different effects, although I think as a class, these calreticulin patients have more similarities than they do differences.

But there has been some literature to suggest that overall, calreticulin mutations are felt to be associated with a more favorable prognosis, at least compared to patients whoa re JAK2 mutant or perhaps triple negative. But specifically those that have the type 1 calreticulin mutation, the data is strongest that they have the most favorable prognosis. So based on that, you could say – the simplest thing is to say if you’re calreticulin mutant, you have a more favorable prognosis.

But perhaps the more nuanced is that that is particularly so for those that have the type 1 calreticulin mutation. In Marsha’s case it’s interesting, and to me a little bit of a paradox in that type 2 calreticulin mutations are, relatively speaking, more common in ET than they are in myelofibrosis.

So in that sense it’s perhaps not surprising that she has the type 2 calreticulin mutation. But overall, of course, ET has a more favorable prognosis than MF so it’s a little, in that way, a bit of a paradox. And the other way to look at this, and this has certainly happened for myself and I’m sure it happens with Dr. Moliterno is these patients with ET or myelofibrosis who were diagnosed many years prior, before calreticulin testing became available, you then tested for the mutation and confirm they were calreticulin once that test became available.

It’s one of those sort of: well, I just confirmed what I already knew which is that they had a more indirect course over these many years.

Andrew Schorr: It’s just amazing. Fortunately we can talk about this, and hopefully the word better prognosis sounds ] great.

So I, with primary myelofibrosis diagnosed with the JAK2V617F gene, Dr. Moliterno. But when you talk about prognosis, now you’re introducing medicines that we haven’t had that long; like for me. I’ve been on ruxolitinib now four and a half years and it’s been working. So how do we – when you talk about prognosis related to genes, though, that relates to what treatments you have, right?

Dr. Alison Moliterno: Right. We have a lot of work because these genes do have meaning; what version you have, and they’re going to have meanings in terms of prognosis but hopefully also we’ll start to gain information about really how you respond to therapy. So far, it seems that it doesn’t matter too much whether you have JAK2 or CALR mutation in response for  ruxolitinib.

But I think as we extend or molecular profiling, maybe we will learn that some lesions are less responsive or less favorably responsive to have some of these agents, and might be more responsive to agents that we have in the future. So I think we have to use this information both diagnostically, prognostically, and also just kind of monitoring our treatment expectations to some of these new agents.

Andrew Schorr: Right, it’s a moving target and I know you have a few things in trials. So just to tie the knot on testing, Dr. Oh; somebody wrote in and said: look, my doctor doesn’t require genetic tests. Where do I start and how do I ask for it? Because we’re hearing the two of you saying it’s pretty standard for you to get a clear picture of what the situation is. So is, how shall I say it, self advocacy related to testing today for an MPN patient important?

Dr. Stephen Oh: I think it definitely is. These diseases, while they’re not super rare, they’re not as common as hypertension or whatnot. When you go to a hematologist or oncologist who does not see very many of these types of patients, they might not be TransDigm on the testing that’s available. And so from that standpoint, I think certainly self advocacy is important. This has been emphasized already but getting to an MPN specialist is important.

If we’re talking about in the workup stage, it’s just sort of imagine different scenarios. There certainly could be a situation where the physician, whether they’re an MPN specialist or a more general hematologist or oncologist; they may not feel there’s a testing and that could certainly be the case.

[00:54:02]

But if there is a strong suspicion of a possible MPN, then I think there’s no question this kind of testing should be done. Even in the situation I’ve encountered with some patients where the insurance may require preauthorization, if you go through that it’s almost never rejected.

Andrew Schorr: Dr. Moliterno, here’s a question we got in from Jane. Jane writes: my understanding is that JAK2 is an acquired genetic mutation, and you both spoke about that; not inherited so we’re clear on that. Is it known what variables cause this mutation? I got the impression from what Steve said, no. But then she asks; can this gene expression be reversed?

Dr. Alison Moliterno: Right. First, why did this happen. I always joke with my patients; I tend to think MPN patients tend to be the most highly educated, intelligent, beautiful and have healthy lifestyles; why would they get this? MPN or not, disease is a lifestyle or other processes that we can sort of point to. I think in terms of if we just focus on JAK2V617F, that’s an acquired mutation in the bone marrow stem cell, but we’ve come to learn that this is a fairly common mistake, acquiring this mutation.

So if you look at my bone marrow stem cells, you can find evidence that this occurs frequently as a mistake; almost like a typing error that we all make on our keyboards, and that this happens at a fairly high rate. Most of the time as Dr. Oh mentioned, it is deleted or it’s in a cell that doesn’t have a long lived lifespan so it really doesn’t propagate in the bone marrow.

 Some fascinating studies looking at the cause of this; what are the factors? So, this Danish study looked at 43,000 individuals that participated in a healthy Danish lifestyle activity. They said they had stored DNA samples from blood. These were well people; they did not have myleoproliferative disease. But they found that they could detect the JAK2 mutation, V617F in a reasonable percentage of these well individuals, and that this was more prevalent the older they got. So that over 80, I think it was .2 percent of individuals actually tested positive for this. They were able to look back and show that yes, most of these people didn’t have an MPN, although some of them did have higher blood counts.

When they followed them, some of them did go on to develop MPN. But the point of that is wow, this is a common, natural occurrence and it most strongly associated with aging. Most MPN patients are in their mid 50s when they’re diagnosed; some very young and some are much older. So again, while gee, 50 isn’t that old, 50’s not that old. So again, there must be other factors that allow that to occur. And these large population studies, I think smoking has been an association; again maybe helps accelerate that mutation growing.

There’s host factors, and that maybe we have reasons that we will make that mistake more often; s genes that we have perhaps that we’ve inherited that influence how well we have integrity in our DNA. So that just gets a little to why did this occur.

Andrew Schorr: What about turning it back, though?

Dr. Alison Moliterno: Right, turning it back and I think this is another thing that is important. Again, when we think about surveillance, we do know there are some therapies that can specifically turn down or squash that clone and I think many of us have heard or even experienced patients who are on interferon, or pegasys, pegylated interferon. And we can see that if JAK2 disease can go into a hematologic remission and even molecular remission that the JAK2 clonal burden reduces and may even go to zero.

This has also been shown with CALR mutation positive individuals in small studies that perhaps we can suppress that. So we hope someday to – it’s still a little frustrating; not all patients have that benefit. It’s not clear which patients will go into these molecular remissions of turning it down.

But I think we will get there and we hope that JAK2 inhibitors would have that effect. I think the data still there are not pointing in that direction, but I think we will ultimately be able to actually target that clone and control how it expands and turn it back.

Andrew Schorr: So Stephen, take us into your labs and into the research that’s going on around the world. How fast is this changing now? Alison talked about 2005 with JAK2 discovery and you had CALR and some of these others. What’s the rate of change now?

Dr. Stephen Oh: I think there’s different perspectives you can look at this. For those of us that are doing laboratory research, we feel in the field that things have progressed quite rapidly.

To go from 2005 discovery of the JAK2 mutation to small molecule inhibitors going into patients I think within two years or less to this one drug being FDA approved a few days later; that pace of discovery and development has been quite rapid. The identification of the calreticulin mutation in addition to MPL, those are really landmark discoveries in this field.

For patients, I think the perspective might be that wow, I wish it could move faster and we kind of know as a class in general what JAK inhibitors do; can we move onto the next level, or next phase, or next class of treatments? And I think there is where my long term outlook is very optimistic, but in the short term we don’t really have that  kind of next candidate clearly identified as to what to do next after the JAK inhibitors.

Andrew Schorr: Dr. Moliterno, we always talk about clinical trials. This relates to the progress you all are trying to make. We’re your partners in that. As you do the testing and you say oh, now we see this gene, and we see this one and this one and we’re trying to figure out who’s the bad guy, or is this new one a factor that we’ve identified? So what would you say to us as we lived hopefully long term with these conditions about considering being in a clinical trial to help you make these discoveries?

Dr. Alison Moliterno: We have had great support from our patients, not only in participating but also helping design these trials or partnering with us. As Stephen said, these are rare diseases so we don’t have 50,000 individuals to test whether aspirin works or not like you can in a cardiology trial, and get that answer in a year and make a difference for individuals.

I would say that the trials now are going to be a lot more molecularly based. So instead of just disease, MF yes or now; these trials are now going to have the molecular profiling and response to therapy as part of their design. I think that will give us a lot more information overall than we’ve had in the past. So there’s many benefits to this molecular revolution.

One is understanding the cause of the disease, the other is monitoring it over time, and then response to trials which individuals respond to; which therapies. I think we’ve all seen the television ads about Keytruda and patients, as you mentioned early on with different solid tumors and particularly lung cancer, and how really the profile of that tumor needs to specific targeted therapy, and that’s what we want for MPN.

 Then now we’re even learning that it really doesn’t matter where a cancer may have started; if it’s in the kidney or in the lung, that again the molecular – the drivers of that indicate that you may respond regardless of what organ it started in; it’s really the lesion that you’ve got. And I think we will be bringing that to MPN patient trials.

Andrew Schorr: I’m involved in an initiative called Precision Medicine for Me, and it started in lung cancer but it is about this testing to see is there either existing therapies or investigation ones that line up. Or F dot now and as you know one of the major cancer medical societies called ASCO, American Society of Clinical Oncology.

The whole mission of the new president, a guy named Bruce Johnson from Dana Farber in Boston, a lung cancer specialist, is that these precision medicine approaches of each patient and their doctor knowing what are they dealing with at the molecular level to push that out throughout oncology; certainly in the U.S. if not worldwide. So I think we’re all in this together. Marsha, you’ve been listening patiently.

Now you’ve had this transition from ET many years, which Stephen was talking about we know often a very good prognosis. But then it changed, and a little scarier. I’ve already started that point, myelofibrosis. But when you hear this, how do you feel, just listening?

Marsha: I think when I was first diagnosed I was scared to death. But I think through education, I’ve learned to calm down and I just try to tell myself that this isn’t a sprint in my case, hopefully it’s going to be a marathon.

And until then, I’m just going to learn what I can do to help myself. I’m very curious about additional mutations; however my doctor said that really would not affect the treatment I would be currently undergoing. And the big thing, insurance, has come about. He’s very concerned about whether or not insurance would cover the cost and the value of it.

Andrew Schorr: Right. Stephen, is this – it sounds like maybe we’re making progress with insurance companies; that they want us to get a clearer picture with our doctor? What’s your take on that now?

Dr. Stephen Oh: The driver mutations, the JAK2, MPL< calreticulin testing, I think it should be and almost always is covered by insurance.

But when you get into the more extensive genetic testing, that’s where the insurance companies will often balk at covering it. Then it becomes somewhat problematic as to is this really worthwhile. Obviously that the costs for it and for any particular patient can vary in terms of what insurance will cover, what the copay is, and what they can reasonably afford. In general, while I do believe that there’s much utility to this kind of testing these days, if the cost is prohibitive I do not push it and I certainly do not think it’s mandatory.

Andrew Schorr: Dr. Moliterno, and I’ll mention to our audience we have a few more minutes; if you have a question and we haven’t covered it, please send in your question to MPN@patientpower.info, MPN@patientpower.info.

Dr. Moliterno, so we have the JAK inhibitor now, ruxolitinib. There are others that are being tested in various trials. As you look not just at the genes but at the treatments, are you fairly encouraged there that you will have a broader array to line up with people’s different situations, and also what the side effects of treatment, if somebody gets anemic or whatever their profile is?

Dr. Alison Moliterno: Yes, I am very optimistic. I think many of us, again if you look back at where we were five years ago in terms of the options that we have and where we assume we’re going to be in five years, hence I think there’s lots of room for application of these therapies, for combination therapies to use therapies together, even the ones that we have. So I’m very optimistic.

And I think I would say it is very anxiety-provoking to hear you need molecular profiling, and yet your doctor is saying we don’t really need that, or we’re concerned about the cost, which is certainly a concern. One thing I always say is that’s fine; the molecular profiling isn’t going to go away as an option, and the cost will come down in the next few years. We are now able to do things that we couldn’t even imagine we could do clinically in terms of looking at all aspects of genes, and this cost will come down.

So I would say to, for instance Marsha, yes we may not need it today but we can always get it in two years when things are different in terms of the availability of it and the interpretation of it. So again, I think it is reasonable to say your treatment is this, you’re responding well; happily we don’t need this at the moment.

I would agree with that, but I’m also certain that in three or four years, we won’t be having this discussion so much about the cost of this testing.

Andrew Schorr: Dr. Oh, here’s a question we got in. you’ve got to decipher this one for us. We have some really smart people out there, like PhDs. Is a germ line ASXL1 mutation a high risk or detrimental factor in the same way as a somatic mutation? So what’s germ line, what’s somatic, and is this germline ASLX1 mutation bad news, basically?

Dr. Stephen Oh: That’s a great question, and I think it also connects to a broader question. But to first answer you, talking about our acquired mutations which is the same thing as somatics; somatic means acquired.

If you’re talking about a germline mutation, in this case ASX01, it’s not the same thing as an acquired or somatic ASX01 mutation, which is what we’re generally referring to when we talk about that gene and its affect on prognosis. That also connects to the more broader point which is that the devil’s in the details.

Whether it’s ASX01 or another gene, the exact mutation may matter a lot in terms of what the significance you attribute to that. In many of the labs that do this type of testing, they will have a column for each mutation where they’ll make a call as to what they think it’s significance is, and they’ll say yes, pathogenic or it will say no pathogenic, or it will say uncertain. Part of that interpretation depends on whether it’s the germline or somatic AKA acquired mutation.

Oftentimes they can’t say for sure because the only way to determine that conclusively is to test tissue that’s not from the MPN. So, sometimes it’s uncertain as to even whether it is germline or somatic/acquired. So again, just to be clear on this particular question; if it’s thought to be a germline ASX01 mutation, it’s unlikely to be relevant or have a prognostic impact on that particular patient.

Andrew Schorr: So Dr. Moliterno, the other question you must get from people is do I have to worry about a family member? Because when they start talking about genes, you’re talking about what your hair color is, or hairline as I was joking with Stephen, or whatever characteristics herein are hereditary.

But then we’d say gee, is there a hereditary factor to an MPN?

Dr. Alison Moliterno: That is a very important question, and long before the JAK2 discovery, we realized that about 10 percent of individuals with an MPN will have a first or second degree relative with either an MPN or another cancer. So there does seem to be heritable factors at play here. Some of the interesting – and again, it’s not because you inherited – in your individual case you inherited the JAK2 mutation from the germline directly from Mom, but you inherited a risk of acquiring it.

We’re trying to understand that and again, what does it relate to; does it relate to germline variation in genes that allow this to occur, that allow you to get mutations in blood stem cells or in other tissues?

So yes, we are still working on that. It does seem to be a component of that. And that’s not unlike CLL, chronic lymphocytic leukemia also has sort of a familial –

Andrew Schorr: And I have that, too. I’ve got them both. I understand. So I think about that all the time. Marsha, you have children, don’t you?

Marsha: Yes, I have two children. But I think even more importantly, I have a cousin who has CML and another cousin who had stem cell transplant for AML. So I think that’s interesting.

Andrew Schorr: This is all in the hematology world, so Dr. Moliterno, do we have, Marcia or me, with two blood cancers? And I have three kids; what about this and is there a testing they should have, or how do we go forward?

Marsha: We don’t have – I would to recommend that they need a JAK2 test or specific MPN testing. If they have normal blood counts and they’re well, they don’t need to be evaluated for disease at the moment. The question is are there family genes that need to be elucidated, and if you have a lot of cancer in the family, so for instance families that have a lot of breast cancer, we often will send them for genetic counseling to understand what their particular risk is. And in breast cancer and some other cancers, we do understand some genes to test that can give us that information; familial genes. So far in the MPN, we don’t really have the knowledge of which genes are at play. 

Andrew Schorr: Dr. Oh, any comment on that because I’m sure you get the same questions. People say oh, my God, should I worry about family members?

Dr. Stephen Oh: Absolutely. It comes up pretty routinely and just to echo Dr. Moliterno, I generally do not recommend any special screening for family members, of those who have an MPN. I would also point out that even if there is, certainly it’s established that there is a slight increased risk for family members of patients with an MPN. Even if the risk was, let’s say, four fold higher for a first degree relative, the overall risk of developing MPN is so low that that overall risk for a family member is so unlikely that they’re going to develop an MPN.

Andrew Schorr:  Really? That gives some comfort; maybe you too, Marsha.

Marsha: Certainly.

Andrew Schorr: We’ve covered a lot of ground over the last hour, and I think on a very important topic now as mirroring the progress related to some treatments either approved or developing is, understanding our slice of an MPN, and the working with you on monitoring that and how does that relate to care. We have two noted experts with us who are helping propel this forward. So we’re your partners in helping that. Dr. Stephen Oh from Washington University and the Siteman Cancer Center, thanks for being with us once again and giving us of your time; I really appreciate it.

Dr. Stephen Oh: My pleasure.

Andrew Schorr: Okay, and Dr. Alison Moliterno, being back with us again from Johns Hopkins in Baltimore; thank you. Thanks for both of you; your very clear explanations, and Marsha Krone, we learned a lot, didn’t we Marsha?

Marsha: We sure did.

Andrew Schorr: Okay. Marsha’s my partner here; she’s done it twice and we’ll have you back sometime, Marsha.

Also, we should tell you Marsha is a very active preschool teacher so she has these little rug rats running around all the time, and thank God you have the energy to do that and I’m really glad you do, Marsha.

Marsha: Me, too.

Andrew Schorr: All the best to you. Well, this has been a wonderful program. We want to thank the Patient Empowerment Network for leading the way in this series, and Incyte Corporation for its support of this educational activity, and Patient Power our wonderful team Alan and Jamie who make it happen behind the scenes. We’ll be having more throughout the y ear. We welcome your questions; always send them to MPN@PatientPower.info.

And all of us moving forward living with an MPN, we’re going to live well and we have wonderful physician partners to help us do that as they understand the genetics and all those people working with them to develop therapies to help us live a long and strong life. Thanks for being with us in Carlsbad, California near San Diego.

I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.

Living Well with MPNs – Tips and Strategies for Managing Symptoms and Side Effects of MPNs

Tips and Strategies for Managing Symptoms and Side Effects of MPNs

As part of our Living Well with MPNs webinar series a panel of MPN experts and patients discussed managing life with an MPN. The panel shared advice on managing fatigue, itching, night sweats, enlarged spleen and other symptoms. The experts explained why symptoms occur and stressed the importance of communication with your healthcare team. Tune in to learn more.

Living Well with MPNs – Strategies for Getting the Best Care

Managing Life with an MPN: Strategies for Getting the Best Care

In this “Living Well With MPNs” webinar, our expert panel featuring Dr. Laura Michaelis from the Medical College of Wisconsin, nurse Erin Blackwell from Levine Cancer Institute, as well as patient advocate Beth Probert, discussed managing life with a myeloproliferative neoplasm (MPN). The panel shared advice for finding a specialist, making informed decisions about treatment and monitoring progress of the disease through testing and check-ups. Tune-in now to hear tips for living well from the perspective of patients and healthcare providers.


Transcript:

Andrew:                                  

Hello and welcome to this program, “Managing Life with an MPN; Strategies for Getting the Best Care.” I’m Andrew Schorr in Carlsbad, California and living with an MPN, myelofibrosis. The Living Well series is a Patient Empowerment [Network] program produced by Patient Power, and we thank Incyte Corporation for their support for this series. We’ll be doing several programs during the year so be sure to be signed up with our alerts and you’ll always know as we continue.

We have some great people with us today around the country. I’m in Southern California, northern San Diego County. Now let’s go to Milwaukee, and I want to connect with our friend Dr. Laura Michaelis, who is at the Medical College of Wisconsin. Laura, thank you for being with us on Patient Power and our Patient Empowerment program today.

Dr. Michaelis:       

Absolutely, I’m pleased to be here. I wish our weather was as good as yours must be.

Andrew:     

Yeah, it is nice. And also I should mention Dr. Michaelis is dealing with a cold, so if she sounds a little stuffy, doctors get sick, too. But thank you for being with us. Now let’s skip down to Charlotte, North Carolina and the Levine Cancer Institute and that is Erin Blackwell. Erin works with Dr. Michael Grunwald who we know well there. Erin, thank you so much for being with us in Charlotte today.

Erin:   

Thank you for having me.

Andrew:                                  

Erin of course deals with Dr. Grunwald with leukemia patients and myeloproliferative condition patients all the time, and won an MPN Heroes Award this past year at the American Society of Hematology meeting for her dedication. Okay, let’s go back to California. Beth Probert is with us from Oxnard, California. Beth is a PV patient and she is just north of LA in Oxnard. Beth, thank you for joining us.

Beth:   

Thank you so much for inviting me to the panel.

Andrew:    

Beth, let’s talk about your story just for a minute. And that is you’ve been living with PV for what, about a year or so, now and you’re 55?

Beth:     

That’s right; just about a year.

Andrew:     

Okay, how did that diagnosis happen?

Beth:  

Well, it was a little crazy. It was during a very challenging time of my life.

I was dealing with my daughter’s mystery illness and sort of forgot about myself, and finally went to have a CBC with a new primary physician. Somehow, a gynecologist – I was visiting a day before I was to get the results from my physician – had those results, and he saw them and freaked out, and pretty much told me to get my affairs in order.

Andrew:        

That is scary for you. So who told you that you had this fairly rare condition, polycythemia vera; where did that come from?

Beth:                                         

Well, the gynecologist hinted at it and of course I fled his office and got my primary care physician on the phone. She called me down a little bit, told me to come in the next day and she suspected that it was that diagnoses but then arranged for me to meet with a specialist, which happened a few days later. So I had those few days of just pure panic.

Andrew:                                  

Now, you subsequently connected with Dr. Ilene Weitz at University of Southern California, the Norris Cancer Center in LA. That’s worked out for you.

Beth:                                         

It’s been fabulous. I went there; it was a fairly long drive and I was telling myself I’ll get a second opinion and a third opinion until I find the right doctor, and I was lucky to find the right doctor.

Andrew:

We’re going to come back to how you communicate with your doctor and a little bit about the treatment you receive and how it’s working. But the thing is, you’re doing well now with the right healthcare team. You’re at peace, I guess, with your diagnosis; you’re going on with your life.

Beth:                                         

That’s absolutely correct, Andrew.

Andrew:                                  

Okay, so Dr. Michaelis, that’s where we want to get everybody to is connect with the right team and doing well with modern medicine. So first of all, she mentioned about connecting with a specialist. You’re a specialist.

There are not that many doctors who see MPNs. Is seeing a specialist, at least having a consultation, knowing what you know about the field today, is that important? You’re muted, Laura. Hit the mute. There you go.

Dr. Michaelis:                      

Sorry about that. I would absolutely say yes, at some point early on seeing a specialist is important. One of the things is Beth’s story isn’t that unusual. The findings in a CBC of something that seems very off, whether or not it’s a very high platelet count, a very high hemoglobin or hematocrit can be pretty unusual for some doctors to see and know how to deal with. Sometimes they respond relatively drastically when that’s not necessary.

I think one of the best parts about a specialist is you’re seeing somebody who’s seen multiple patients with your presentation, with your symptoms, who knows when to be alarmed and when not to be alarmed. So Beth did exactly the right thing, which was make sure she then grounded herself with her primary care doctor, and I’ll say most of the patients that get referred to me are either referred to me by a primary care doctor, or sometimes by a specialist who might be a hematologist/oncologist.

But this is a rare condition even among people who see heme and oncology, so sometimes a hematologist/oncologist will want them to see me because I see this very routinely, and have seen patients at all edges of the spectrum.

Andrew:                                  

Of course then as we talk about MPN, so everybody’s straight on this and some people may be new to it; talking about ET, essential thrombocythemia, polycythemia vera, which is Beth’s situation; and myelofibrosis, which has been my diagnosis since 2011.

In this program, we’re not going to really get into treatments and genomics and all of that. We’re really going to talk about how do you live well and get the best care. And it’s not just your relationship with the doctor. So, Erin, let’s talk about that. You work hand in hand with Dr. Grunwald. You’re part of the leukemia doctors there and the doctors dealing with blood cancer. The nurse plays a key role, and that’s part of the dialogue, right? And you’re specialized.

Erin:

I think so. I think it’s a very different role than the provider, but we are healthcare providers also so we get to nurture the patients in a little bit different way. We’re not diagnosing but I think we’ve spoken about this before; patients usually have a very good relationship with their provider but they tend to open up to the nurse or the person that they get close to, which oftentimes will be in the office setting, the nurse.

So I think I’m able to glean information that the provider didn’t about symptoms that they’re having, that maybe they didn’t share with the provider; medication issues that didn’t come up.

So I think our relationship – and I’m the bridge, is sort of how I phrase it to patients. They can always go through me to get to the provider. If they’re not sure they need to contact the provider; I’m sort of the middle man.

Andrew:

Let’s start at the beginning. Beth, when you’re OB/GYN was freaking out if you will; did you see those blood test results and see how abnormal they were?

Beth:                                         

I absolutely did, and I was joking with you earlier that not only did I see some highs on there; I saw “critical” written next to several of those results. So that was extremely alarming.

Andrew:                                  

Dr. Michaelis, most of us with any of these conditions see Hs and Ls and critical that she saw; notations from the lab. What does that mean to you?

Because we start freaking out until we learn more.

Dr. Michaelis:                      

Of course it’s important to remember that when somebody comes up with what is normal, it’s done by having let’s say 1,000 people go to the hospital, have their blood drawn, and then a bell curve is written as this is what the normal hemoglobin is. What’s important is not so much if somebody is one or two points outside of the edges of that; it’s important; what it is relative to Beth. So for example, if Beth starts at a given level and then over time, her disease gets under control, she may still be slightly high or slightly low in some zones.

But relative to her, the disease is getting better. So we don’t really pay attention to the highs or lows very much; that’s against a huge, general population. What I’m really interested in is what do Beth’s labs look like compared to where they should be, or what it would mean if her disease was well controlled.

Andrew:                                  

So you deal with that, too, Erin, is people have a test and they’re alarmed. You often have to, as I say, bring people back down to earth, right?

Erin:                                           

Yes, and unfortunately when we print labs for patients, it actually will print out “high, low, critical” so patients do become frightened. We have a really neat tool on our computer system where we can graph counts over time. So I can show you from last year where you’ve started and where you’ve come to, so you can see the improvement, hopefully, and at times not improvement. That seems to calm nerves.

Andrew:                                  

That does it for me. So okay, Beth, you started seeing a specialist and then you had a certain rhythm of visits now that you’ve had over the last year. How often do you go see Dr. Weitz?

Beth:                                         

I see Dr. Weitz now about every six weeks. At the [00:20:00] onset it was every two weeks and four weeks. But because I am doing much better, it’s now six weeks.

Andrew:                                  

Right, and we should mention in your case, your one of the folks with PV who is on an interferon. The dose has been adjusted but it’s working well for you.

Beth:                                         

It’s working very well.

Andrew:                                  

Okay, so Dr. Michaelis, let’s talk about how you establish a treatment plan. So we come in, you confirm the diagnosis, we have some tests. So, how does that dialogue go about not specific treatments but how do you establish a plan?

Dr. Michaelis:                      

That’s something I’ve learned as I’ve matured as a doctor, and I feel it’s something I’m getting – I hope to get better at. I start everybody by talking about what is the cause or what do we think the causes of the disease are. I think it’s helpful for people to understand the way the disease develops, what are the underlying levers and changes in the bone marrow.

And then we talk about 1) have we truly confirmed the diagnosis? Do we have all the tests we need? Once we get through step one, which is confirming the diagnosis, we then go through something called risk stratification. Risk stratification means that we look at what does the disease look like, what are the characteristics of the disease. Are there high risk characteristics or low risk characteristics?

We then look at the patient’s own medical history; their age, their other health issues, their what we call comorbidities; the other things they may be struggling with. And the combination of those two help me determine what’s the likelihood of something bad happening because of the disease, or how the disease interacts with the patient. Once we have that risk stratification, then I like to talk about goals. What are this patient’s goals? Some people want to do everything they can to eradicate a disease.

Some people, their important values are their quality of life or being at home with their families. I try and listen to their values and what’s important to them, and then with that, we think about this is the risk the disease poses. These are the goals that you have; what is our panel of options out here? What kind of arrows do we have in our quiver, and how should we choose that treatment based on what we can accomplish, what you want to accomplish, and what we ought to accomplish.

That ‘s the kind of dialogue, and I find that that conversation, not the one where you’re first diagnosed, but that conversation of the first discussion of should we start treatment, that’s one of my longest conversations. So I prep patients; this might be a conversation where you want to bring family members. This might be an appointment we’re going to make as a double length because it’s going to be a little bit longer. Sometimes we’ll have patients bring their iPhone or something so they can have other family members conference in.

But that decision about starting treatment and which treatment to go for and why is an important one. And finally, we end it all by what should we see if it’s working. So how are we going to measure that this treatment is working for you? What are the types of things we’re going to see, and when? And when will we know when it’s not working?

So I like to lay it out with saying have we gotten the diagnosis, do we have appropriate risk stratification, have we identified your goals, and what kind of treatments are out there that could accomplish your goals.

Andrew:                                  

I was living in Charlotte for awhile so I went to Erin’s clinic and to see Erin and Dr. Grunwald. We would talk at each visit based on what Dr. Michaelis was just saying: how am I doing, how’s it going; bout a frequency visit. Sometimes I’ve had doctors say to me, when do you want to come back? Then I’d say doctor, when do you think?

Well, I think you should come back in three months. Sounds good to me, or should I come back sooner? Erin, you’ve been part of those conversations about frequency of visits. How do you as a team determine that with the patient?

Erin:                                           

I think it’s really; again as Dr. Michaelis was referring to, it’s a conversation had by the physician, the provider; what they’re comfortable with versus what the patient is comfortable with. At times, it’s that the patient would like to be seen more frequently than they really need to be for their comfort and their peace of mind. And the physicians usually are okay with that.

Then there are times when they want to go six months without follow up, and obviously with a lot of our patients, unless they’re just doing very, very well, that’s not feasible or responsible. So it’s always a conversation and I’m the one to make their follow up appointments and to give that to them when they’ll leave. So I’ll be the last line if they have an issue with it; they let me know.

Andrew:                                  

Beth, how often do you go? How often do you see Dr. Weitz?

Beth:                                         

Now I’m seeing Dr. Weitz every six weeks, and I really took to heart what Dr. Michaelis and Erin just spoke about because it’s the process I went through. What makes it very comfortable for me now to go every six weeks, I know whenever I have a question I can reach out to Dr. Weitz through the portal email. And it’s amazing; she gets right back to me. So it helps bridge that time going from two weeks, then to four weeks, and now it’s six weeks. I don’t feel alone. I don’t feel like it’s too long because I know I could reach out to her and her support team, as well.

Andrew:                                  

Okay, let’s talk about phone calls and emails. Dr. Michaelis, are patients able to call you? Do you communicate either directly via email sometimes or through the portal that maybe your institution has – many have it; I have it at UCSD here – about visits or connection, if you will, or questions with you or your team when you’re not physically there; when the patient is not physically there?

Dr. Michaelis:                      

Absolutely. One of the technologies that is possible now because of these electronic medical records allows what we call asynchronous communication. So you wake up in the morning and you’re much itchier than you’re used to, or you have a rash, you email me. You don’t have to reach me at that exact moment in time, but I will see it. My nurse sometimes screens it, and if it’s something she thinks is more urgent she’ll walk it over to my office or she’ll page me.

If it’s something that can wait, there’s a given period in the day when I take a look at the messages that have come in, that I’ve set aside and I’ll respond to them. Sometimes a patient wants to talk by phone, which is great. And that, I always ask them leave me a time that’s a good time to talk to you; best for me after 4, before 6. And that’s a time when I tend to be able to communicate with patients. I think one of the key elements is to remember, these are not for something urgent.

If you have chest pain, if you have severe shortness of breath, if your leg gets suddenly swollen; don’t expect these emails through the electronic medical record to be that timely because it’s often something that’s done as a routine part of the day but not urgently. Those should be done by a page, and everybody should have a way to page your doctor or their nurse through a triage system. Or, if it’s a real emergency, of course go to the ER or call 9-1-1.

One of the other things I do is I give my patients a stack of cards. Because if they’re being seen in an emergency room or somewhere, I want them to give my card to that doctor and ay: this is my hematologist, I have a rare blood condition; please page her. That’s because sometimes folks live far away from me, and so if they’re up in the upper peninsula of Michigan or skiing somewhere and they have an emergency; their bleeding risks, their clotting risks are unique.

I want people who aren’t familiar with this kind of blood condition to be able to call me any time and I can say this person has PV, they’re on a low dose of hydroxyurea; these are the things you need to watch out for. If the person needs to go to surgery emergently, this is what needs to happen afterwards. So I always have my patients carry a stack of cards to distribute. And I say don’t assume any physician knows about this condition; please have them contact me.

Andrew:   

That’s a very cool idea. I hadn’t thought about that and they hadn’t told me that at UC San Diego where I go. So, now we’re going into travel season, Erin. So people may go far afield. Esther and I are actually going on a business trip to Europe; hopefully everything will be just peachy fine. So talk to me about travel.

People have anxiety with illness when we travel, and if we have a wonderful relationship with you or Dr. Michaelis, or Beth has with Dr Weitz in Los Angeles, when we get away from that tether it can be a little anxiety-producing. What do you say to people about travel, particularly as we’re looking at the travel summer season?

Erin:                                           

It’s usually a conversation at the appointment. If our patients are going to go out of town for any reason, there’s a risk of interrupting treatment or they need labs while they’re away; that’s something we can help them set up. We have a patient currently that travels to Florida every other week and is on treatment. So we worked with an institute in Florida to sort of split care. So it’s a conversation that needs to be have. And I think fortunately, our patients have direct access to us almost 24/7.

We have an Access Center that takes calls 24/7, and during the day will reach a nurse; at night a physician covers. They always have my email address, my direct phone number at my desk. So, we try to make ourselves very reachable, so if something does come up –

But as Dr. Michaelis was saying, if anything urgent and life threatening comes up; call us later and go to the ER first, that sort of thing. We reiterate those messages.

Andrew:

I’m going to come back to you in a second, Beth. Well, Beth, let me ask you this while I’m thinking about it. From the patient point of view, like I don’t know what your travel plans are. You’re giving yourself interferon shots. Do you worry about travel at all because of PV? How do you plan your life? Because you have your doctor visits, you’re giving yourself shots. How do you plan your life, and do you worry about disrupting that plan at all?

Beth:

You know, on the onset I absolutely did. When everything is running your mind, and at the time I was traveling more. So my doctor actually talked to me about if I do need to take it with me, that the airlines, you know, what they require. And she urged me to check the airlines that I typically travel to get the instructions; does it need to be refrigerated, what are the security risks?

So, I sorted that out when I first went on the medication. I was doing a little traveling for business. And of course now that I’m on an every other week dose, it does make it quite easier. But I do urge PV patients to figure that out in advance, even if it’s just a slight – Maybe it might happen, maybe it might not but to be prepared in advance is something so important. So I did check that all out.

Andrew:

Laura, you were talking about eventualities that come up for patients and the communication among doctors. For instance, I have minor surgery that I’m trying to have happen. And so in my case as a myelofibrosis patient, I have lower platelets. And so I’ve got the surgeons talking to my hematologist/oncologist and they’re going to be prepared with platelets for the surgery so I can have the surgery; they feel it’s safe.

But they planned for it and they’re all talking, and that’s the kind of thing we need to ensure is happening, right?

Dr. Michaelis:

Oh my gosh, yes. I think communication between physicians is absolutely essential in this, especially when a procedure is elective. That means there’s time. Elective is a term we use when something can be done and planned in advance instead of emergently. We do know that when patients with PV, for example, go to surgery and their hemoglobin is very high, their risk of clots after the surgery or even problems within the surgery with the anesthesia can be higher.

So you want to make sure you’re going in – to the best of your ability, you’re going in with your blood counts well controlled and under optimal management. Same with platelet counts, which elevated platelet counts after surgery, can sometimes be a problem.

The other thing is that when your doctors communicate, it means that there’s a transfer of information, there’s a transfer of knowledge. And so that surgeon, when they go to see you and does his post-operation visit, it’s going to remind him: oh yeah, this patient has that rare condition; maybe I should call that doctor and just update them, for example.

So starting that communication early and that transfer o f knowledge is not only good for you, but makes sure that there’s a sort of routine – there’s a routine collaboration on a complicated patient.

Andrew:

So Erin, what do you tell your patients so that they get everybody working together? You try to do it within the hematology area, but somebody might have diabetes, somebody might have heart issues, somebody might have whatever surgery, procedures coming up. So how do you counsel people so that you know what this condition is, that we’re living with this hematologic condition is understood and proper communication happens?

Erin:

Similarly to Dr. Michaelis, Dr. Grunwald and Dr. Gerber both give out their cards to every patient that comes to the door. They hold onto it and they know if they see another provider and there are ever questions, that they can give them the card or give them their information. Something we don’t think about all the time when we’re treating these patients with either acute leukemia or myeloproliferative neoplasms in this case, they oftentimes have comorbidities or other things going on that we have to also address and make sure they’re staying – if they do have databases, we’re monitoring their A1C and their sugars are controlled.

And just because they have this diagnosis in myelofibrosis, that they’re not forgetting to take care of the other parts of their bodies. We need all parts to work, so I think it’s really important when I see patients – I look over their labs and their vital signs and make sure we’re addressing the things that sometimes we accidentally tuck away, like if a patient’s blood pressure has been continually high and we’re not addressing, or if their sugars have been high and we haven’t checked an A1C.

I think the best thing we can do is educate patients to know those sorts of things and to know what to look for so they can be advocates for themselves. But I think it’s also important that we all are mindful of the different parts of the patient because most of our patients are pretty complicated. There’s not just one thing going on.

Andrew:

Right. I have a question for you, Dr. Michaelis. So frequency visits, just to go back to that, if you want to see me more often does that mean things are not going well and I should start – my blood pressure should go up and – you know?

Dr. Michaelis:

Not always. Certainly if I get worried about a patient, my solution to that is to pay more attention. So sometimes if I’m worried that somebody’s disease is progressing, I will see them more frequently. But more often, when I see somebody more frequently it’s because we’ve had a turn in the road.

It might be a change from hydrea to interferon. We might have changed the dose of interferon a little bit. I might be worried about –. Maybe it’s the time of year, for example flu season. A lot of patients in the fall, we have a lot more hospitalizations with all leukemia patients and also some MPN patients. So sometimes it’s just that – I usually, like Beth’s experience and Erin’s experience, the frequency of visits is often a conversation. I’m not somebody who can go to long without seeing my patients. I want to keep them close so that I monitor them.

But if somebody is getting labs, they live in the upper peninsula of Michigan, they’re getting labs every six weeks and seeing me every 12; that’s fine and just keep up with that.

Andrew:

Right. I want to mention to our audience, so we have time for your questions so send them to MPN@PatientPower.info. We’ll get to the ones we can today, and we’ll be doing a whole series of these programs and so we’ll just keep making sure that we cover what’s important to you. I want to mention in my case as a myelofibrosis patient, that Dr. Jamieson down here in San Diego, she has me go to one of their clinics within the UCSD system and get monthly labs. And then if there’s something she’s concerned about, they let me know. But otherwise, I’m on a three- or four-month schedule, whatever it may be.

Okay, let’s move on to some other things. We talked about the treatment plan, Dr. Michaelis; you talked about that. One of the things that can come up in treatment planning now today is hopefully we have a situation that continues to involve in MPNs, is clinical trials.

So you’re a researcher as well as an in the clinic clinician. So where does that fit in in the discussion, in your opinion, related to what clinical trials are happening, what might be coming, what should we put on the table for our ongoing discussion?

Dr. Michaelis:

Great question. I think there’s this false idea that clinical trials are something that are used as a last resort, and it turns out that that’s really not the case, not in MPNs and not in other conditions as well. So, clinical trials are where there’s a hope to either improve or change the standard of care. When a patient is newly diagnosed, there is oftentimes opportunities to be in a trial that might be providing the standard of care with something else, or might be testing some new agent against the standard of care.

In myeloprolifative neoplasms are one of the most novel agents; there’s a medicine called ruxolitinib which is the brand name Jakafi, and that was only approved because people participated in clinical trials and found that it was effective at the goals that were set out in the treatment of high risk or intermediate to risk myelofibrosis.

So when I talk to patients about clinical trials, I frame it again in terms of the risk stratification, what are our goals, what can we reasonably hope to change, and when should we try and do that; and I put that in the panel of options. So option No. 1 might be standard of care, option No. 2 might be a wait/watching approach; let’s just observe for awhile.

Option No. 3 might be participating in a clinical trial. Clinical trials become more important, I think, when the standard of care options haven’t worked, So in a patient that may have progressed through several lines of therapy. so in a patient that may have progressed through several lines of therapy.

Then looking even farther afield for clinical trials, newer agents, agents that are brand-new out of the lab are often tested only in a handful of spots around the country. And for people with the desire and the wherewithal to look for those novel agents, again far afield; if that’s something logistically possible. And if it’s part of your value system to be involved in something very experimental where there’s no guarantee of success, then looking into clinical trials might be helpful.

Some people don’t want to be in an experimental situation, but some people find value in being part of the process to discover new drugs. And that’s something that’s an important thing to explore with your doctor.

Andrew:

I’m just going to make my pitch. I also have another blood-related condition, chronic lymphocytic leukemia. I was in a phase II trial for that.

I got the combination therapy ten years before it was approved by the FDA as a combination. So I think that helped with my longevity. I’m on ruxolitinib, the drug you mentioned. I was not in the trial but I got it early after it was approved, and I’m very grateful, very grateful. I met even who I think was patient No. 1, Mike down at MD Anderson, and I’m very grateful; I’ve given him a big hug, you know? And so I think it’s something to consider.

Your interferon is working for you, Beth, but there are other interferons in trials and other medicines in trials should you need it. What’s your take on trials? Because I know you’ve been going, looking at all our programs and learning about it. What’s your thought about it now?

Beth:

Let me preface this by saying when I was first diagnosed, I knew I had to remain open-minded. There’s no black or white; there’s a lot of grey.

So I gave myself the commitment that I would listen to everything that’s out there that’s pertinent to me. And somewhat what Dr. Michaelis had said a few moments ago is let me identify your value system. So taking all that information in, I would absolutely consider being part of a clinical trial if it was going to benefit me or have the opportunity. And I agree again with Dr. Michaelis that it probably would depend upon where am I at. It might be working well for me today, but maybe six months, a year, two years –

The other thing I realized right away is that in as much as we all do have very rare diseases we’re speaking about today, things change. The ongoing research, what might be happening today, six months from now might be very, very different.

So taking all of that into consideration, and I do have a very strong goal for patient advocacy and hoping that my journey through this medical challenge is meaningful and could provide hope and care for others in the future.

Having said all of that, I would definitely remain open and just take the situation as it comes along.

Andrew:

Right. What a great attitude. So Erin, that comes up in your discussion. You have Drs. Grunwald and Gerber who specialize in this. I would just make a comment, so your doctors there, Dr. Michaelis in Wisconsin, other doctors we’ve mentioned along the way; these are specialists in these conditions. If you think about companies that are sponsoring trials, they’re going to go to these doctors and say would you be interested in doing this trial. So if you want to particularly have access to trials in MPNs, you want to be connected with the specialists in our conditions, right, Erin?

Because you have research going on there, right?

Erin:

We do. We have several clinical trials open at the moment that are pertinent to this particular set of patients. We don’t have every trial that’s open, but they’re also familiar with what institutions do. So, if we have to make a referral outside because of patients interested in a trial that we don’t offer, and that’s something that we routinely do.

And I just want to point out; you mentioned travel and being prepared. Because of an experience that happened recently, make sure if you travel that you take your Jakafi with you if you happen to be on it, because suddenly stopping Jakafi is not a good thing, as we educate our patients.

Andrew:

And don’t put it in your checked luggage

Erin:

Right, right.

Andrew:

Keep it right with you. I keep it so close to my heart, Erin, I understand. Jakafi, I know, it’s not something you want to stop.

Erin:

Yes, especially suddenly. It should be tapered if it’s going to be stopped or else there are withdrawals.

Andrew:

No, I’m very careful about that. Okay. So Beth, you’re living with this diagnoses that you’ve had for a year or so. So, how have you gotten your head on straight about it to go on with your life?

Beth:

Well, I knew right away that if I looked at my diagnosis as somewhat of a gift, and I mean that by I was running around, I had so many other priorities, I had no clue that anything was really wrong with me. And I shudder to think what might have happened had I not gone for that CBC. You know, I really had a very serious medical condition at the time.

And so I took the attitude that I need to be gracious I was diagnosed, because looking at the alternative, it could have had terrible consequences. And I realized – you know, it took me a couple of months to get my feet back on the ground, so to speak, to just be calmer.

And I really had to start doing some things that people had always said. Oh, you have to have balance in your life. Or you should exercise more; you need to take time out for yourself, or you need to meditate. And I just realized that I need to really be more balanced, mind, body and soul if I was going to go through this medical journey.

So I started doing some different things that worked for me. I wasn’t so good sitting there meditating, but I learned to meditate and walk. I started embarking on yoga. I really embraced myself in a plant-based diet for various reasons. It was working well for my daughter for her autoimmune and I thought there was a lot of merit for helping me. And with that came learning how to cook again; with cooking came more peace and time to think.

I know that’s sort of a long-winded answer but I had to do things differently to be able to understand that I want to live life to the fullest. And if I’m running around always worried, freaking out about this new diagnosis and my medical challenge, I wasn’t going to make it. I really had to be balanced mind, body and soul.

Andrew:

Well said; I think that’s true. So Dr. Michaelis, you have people come in. Whether you make the diagnosis or confirm a diagnosis, they’ve come from somewhere else and they’re pretty alarmed. The family members are alarmed as well. Yet, all of us want to take back control. We feel out of control; this disease we have never heard of. How do you help people? How do you counsel them so they can go on with their lives?

Dr. Michaelis:

One of the things I do is tell people that I’m paid to worry; you’re not.

My job is the worrying job; your job is the living job and so let me do the worrying. You know, I’m used to worrying about these things; I know what to worry about and that’s my job. So my job isn’t cure; I try and heal but I’m not a curer. I try to heal the best I can. If something is curable, I’ll do that. But I am good at worrying. So, that’s what I tell people to leave in the office.

The second thing is that most people have gone through episodes of their lives before where they’ve felt out of control, and things get you through that. Either your family, or the people you love that are around you, sometimes exercise or meditation. Sometimes it’s venturing back into positive habits like good eating like Beth was talking about, or being outside in nature. Some people are grounded in faith. Something that makes you feel bigger than yourself; those same strategies are helpful when you face the grief of a diagnosis like this.

And it is a grief. You’re leaving behind a perception of your body that’s not true anymore because you’ve been diagnosed with some crazy disease that you’ve never heard of. So it is a process. I would say Beth, three months is a great time to be able to have gotten grounded again, and I think the strategies that you used in sort of learning from your daughter is incredibly positive.

But you’re right; this is a new chapter for people. Like, you thought you were traveling along in one country and then the road took a turn and you’re in a different country. So you just have to sort of say well, I want to drive safely but I also have to enjoy the landscape here. So, that just means you have to adjust.

Andrew:

I’m just going to make a comment as someone now living with myelofibrosis four and a half years. So, it was terrifying and my spleen is somewhat enlarged so it’s a reminder that it’s there.

I have my medicine right next to my toothbrush morning and night so I’m reminded then. But the rest of the time, I just go about my business. And I think, and Beth you can probably relate to this, and I’ve said this a number of time. In our lives we have people say can you go on a hike with us, or can you come over for dinner, or can you take ten minutes and let’s get coffee? And often the answer is no because you’re so busy.

I’ve routinely tried to make my answer yes. And Beth, I don’t know if you, too, maybe you could say stop and smell the roses but it’s take time out to enjoy.

Beth:

I could not agree with you more, Andrew. I realized that I was just going a mile a minute all the time, and putting things off and people off.

And you do, you really do reflect on who that inner circle is that you want around you, and making time for them and enjoying that time. So yes, I absolutely agree with what you just said.

Andrew:

Erin, I’m sure you’ve had patients who’ve seen Dr. Grunwald or Dr. Gerber maybe for the initial diagnosis. They’re really troubled. And then over time, how have you counseled people to help them really just go about their lives, enjoy their families, enjoy their work, travel, whatever is important to them?

Erin:

I think that’s the key is finding out what is important to them, and then you can really help them understand that although this is a diagnosis that affects how they live the rest of their lives, and in no way should we minimize that. But we also want them to be able to do what you do, where you take your medication and you go about your day the way that you would like to. I think a large part of the reason our patients don’t always do that is how they feel.

A lot of times they suffer from fatigue, either from anemia or secondarily or just from the disease itself.

It’s hard for them to feel up to doing those sorts of things so I think it’s really important to find to what kind of lifestyle they lead, how we could maybe improve upon that, and then involve any members of the interdisciplinary team that we need to. Sometimes patients need social support, sometimes they need – we have a social worker on campus that’s able to help patients especially with that first visit it they’re having trouble coping.

We have resources available that can help these patients. But I think the key to it is understanding what life looks like to them, what they enjoy about it, what’s important to them, and how we can get them back to doing those things.

Andrew:

Amen. So Dr. Michaelis, let’s talk about communication, not just the emails and the web portals and phone calls, but sort of transparency in communication, if you will. So, that’s on a number of levels. You mentioned fatigue, Erin, and fatigue, I’m fortunate I think I really haven’t been affected by it in any big way.

Beth, I’m not sure about you but there are things sometimes that we don’t confront, or don’t make positive adjustments to. How do you help people first of all communicate about what’s really going on? You mentioned a phone call about itching awhile ago. But whatever the symptom may be and where you all put your heads together to say how can we help you live well, deal with this, improve it if we can, and if we can, what adjustments can we make? Let’s talk about that open communication.

Beth:

Absolutely. One of the things is Erin is absolutely right; this cluster of diseases has a lot of symptoms. And it used to be that policies looked at the blood numbers and said ah, they’re not that bad; you’re fine.

It’s the work of Dr. Mesa who really brought this idea of symptom management and identifying and quantifying the symptoms that patients have, that has led us to be able to say the people with myelofibrosis and myeloproliferative neoplasms are more tired, they have more difficulty; we’ve heard about the itching and the bone pain. There’s also more difficulty sleeping, more chances to depressions, sometimes difficulty fulfilling work obligations. So, truly there are some symptoms.

Now, some of those get much better. They get better sometimes with medications, for example. They can get better if the anemia is well controlled. We do think that probably exercise is helpful, although there are still clinical trials going on with that. But your doctor is never going to know if you don’t tell them. And if the doctor doesn’t ask on a routine basis, and have you really used some metrics to quantify it?

So some of us use surveys. Every time a patient comes in, they might do a certain survey that says: in the last week, how often have you been in pain? For the last week, have you noticed depression? Or for the last month, have you found more difficulty sleeping?

Those kind of things, and we can compare just like you charted your CBC over time; you can also look at your symptoms over time and it’s something quantifiable. It also gives you a hard number to measure; is my treatment working? Look, you say you don’t feel differently but look what you were saying your pain was before, and look what it is over the last three visits. So that helps to really bring people back to the fact that while things aren’t perfect, maybe we’ve made some improvements.

But I absolutely think that not only keeping a diary of your symptoms at home, so if you just keep a little three-ring binder or something that says I notice that my migraines are happening at once a week versus twice a week as before; making sure you arrive at that doctor’s office with data in hand can be really helpful at grounding them back to the fact that this is a symptom-based disease, a lot. And if you don’t treat the symptoms, you’re missing a key part of helping that patient thrive.

Andrew:

Erin, you’re nodding your head. And I know when you walk into the Levine Cancer Institute, you give us a clipboard.

There’s stuff to answer, and they do that in San Diego. Maybe you have that, Beth, at USC in Los Angeles, as well. So that, really being honest, the patient, and maybe the family member saying – if they’re with you – hey, you really haven’t been sleeping well. You really have been avoiding taking a shower because you said you’re having itching. That’s important, right?

Erin:

Yes, sir. And it’s sort of funny. These are constitutional symptoms that the patients feel. We give them an assessment every time they come to see us; one on their initial consultation that’s slightly different, and then subsequent follow up they’ll fill one out that is the square of 100, based on their symptoms. The max score, if they had every symptom at its worst would be 100; and if they had no symptoms, it would be a zero.

So we are able to track the progress. But it always tickles me that a lot of times the caregiver will fill it out on the patient’s behalf. Sometimes we might get more accurate information that way because the patients don’t want to complain, per se.

So the caregiver knows they’ve complained to them, whereas they don’t want to complain to us so it is interesting to see.

Andrew:

Okay, let’s go on and take some questions. And if you have a question, send it to MPN@PatientPower.info. Laura, this one’s for you. This is from Sandra. Sandra writes in: 2012 through a number of blood tests, I was diagnosed with an unclassified MPN. I see a hematologist once per year for blood work. My chart currently says MPN disease stable, and I’ve never been on any medication. Is it possible to be unclassified or are my doctors just waiting for the disease to progress?

Dr. Michaelis:

There is definitely a condition called MPN-NOS. That tends to be something called – it often is an MDS/MPN overlap.

I will tell you the World Health Organization recently redid their numeric – the way they sub-classify these. So one thing you might want to ask the next time you see your physician is, is my disease still classified as MPN-NOS? Or does the new WHO diagnosis, the new WHO classification give me a more precise definition? I will tell you also that sometimes repeated bone marrow biopsies, or at least a second bone marrow biopsy might be necessary to see what’s happening at this time.

Diseases evolve over time, so if it’s been five years since your last bone marrow biopsy, and if somebody is considering treating you, then I would certainly get a repeat bone marrow biopsy to get an accurate picture of your diagnosis.

Andrew:

Okay, here’s another question probably for you as the provider, here. I believe the name is Maria; could be Maria but I think it’s Maria. Or, we’ll call her Mari.

Does a B2 vitamin supplement, 1 milligram tablet a day orally, do any harm for a patient with PV? And then she also asks about other supplements such as valerian root or melatonin.

Dr. Michaelis:

About the B vitamins, I don’t know that it would do any harm. We do tend to avoid too many vitamin supplements in the early phases of these diseases because these diseases are where the bone marrow is growing on its own. It’s kind of like it stopped listening to the body’s controlling signals and the stem cells, which are the interior parts of the bone marrow, are growing without control and that’s why people’s hemoglobin or platelets are high.

So you don’t want to feed that. I don’t think it’s dangerous to take the B2 vitamin, but I also don’t know what help it would have.

With regard to a supplement like valerian root, that’s not really – I don’t know anything about that. What we have here, for example, is a specialist – is somebody who deals with alternative – she’s a pharmacist. She knows a lot about alternative medicines. And what I ask people who are interested in taking a lot of supplements is to have an appointment with her and verify that nothing is going to get in the way of the therapies that I provide. Because I’m responsible for the toxicities of any therapy that I administer. And so what I really want to make sure is that no supplements are going to hurt in that way.

Melatonin is a relatively common supplement. It’s excellent for sleeplessness that happens to be about circadian rhythm so your light exposure. I think it’s especially helpful in the northern part of U.S. I’m here in Wisconsin, and I’ll tell you it’s hard to readjust your sleep when you’re going from a 14-hour night to a 4-hour night based on where you live. It can be helpful and I don’t think that there’s much danger that’s been reported to melatonin when used as directed.

Andrew:

Erin, I know you have a pharmacist – I’ve met him – there at the Levine Cancer Institute. So checking in with the pharmacist about prescription medicines and supplements; that’s not a bad idea, is it?

Erin:

We actually have four dedicated pharmacists to our clinic, but it’s not just us; it’s lymphoma, myeloma and leukemia clinic. But yes, we use them frequently. They’ll consult with patients and at routine visits, they’ll check in. they actually have the ability to make patients – they’re essentially really nice medication lists that tell them when to take their medications at the scheduled time. It’s a printout for them that helps them organize when to take their medications.

So the pharmacists are very involved, and if I ever have a question about a cold medication; will it interfere with the medication they’re on, or supplements, then I will start with the pharmacist and go from there.

Andrew:

Okay, let’s go on.

Here’s a question we got from Judy. Judy asks: I’m finding it difficult to coordinate care among my doctors. Do you have tips on accomplishing that? She say: not all of my doctors are interested in being part of these communications. So Dr. Michaelis, you passed out the cards but how do we make it happen when we, the patient, and maybe you helping us with a serious condition, know it’s really important?

Dr. Michaelis:

It’s hard to change other people’s behavior. I think you offer. I think another thing to do is when you go to your hematologist, ask if a copy of the note, the consultation note, can be also sent to you so you can keep at least copies of some of the written communication that’s happening.

You can’t fix bedside manner. You can find doctors who have good bedside manner, and don’t be afraid to shop around. Nobody gets offended; you’re not offending anybody.

If you find a doctor that doesn’t want to listen to the other people taking care of you, then that’s a concern. People should be collegial. You’re the only person in the room that matters so treat it like that.

Andrew:

Amen. Actually, we have an email from Charlyn that’s related to that. She has this question: What if your hem/onc doctor does not want to give you a referral, such as to a subspecialist like you? She’s saying we’re close enough to be seen by a specialist at Stanford, so in northern California, but need the referral to have it covered by our insurance. So the more general oncology maybe doesn’t want to let go, and you have to go based on insurance. Any thoughts about that?

Dr. Michaelis:

It’s not something that I encounter that much because I’m on the receiving end of that. I guess I would, like every human interaction, I would explore about why.

Why do you not think I should go up and see? If it’s about – I just want at least one consultation to make sure I’m keeping up with things – I’m not sure. It may be that the physician doesn’t think that your disease is serious enough to be seen by – that you need to be seen at an advanced or a tertiary care center. And then maybe there’s a limitation in the number of referrals you get and they want to wait until you actually need to be seen for something where things are going in the wrong direction.

But I would just treat your doctor like a human and ask them why not; let me know. And sometimes you even have to set up an appointment just for a conversation. Just say I’d like to set up an appointment to come in, have a 20 minute conversation where you just say this is what I want to explore with you; that kind of thing. When in doubt, just ask why.

Andrew:

Right. I think be a consumer, Beth, right? You’ve got to advocate for yourself.

Beth:

That’s absolutely true. And you know, it’s important to educate yourself and as Dr. Michaelis said earlier, we’ve lost control when we are affected by these types of diseases. Sometimes that might be within the conversation, too, with your oncology/hematologist to say I believe I would have more control if I also explored having a consultation or working with an additional specialist. And it’s reminding your physician that it is about you gaining control and empowering yourself to be educated. And part of that educating might be expanding your team of care.

Andrew:

Okay, I’m going to do one more question and then remember, we have a whole series of these programs.

This came in from Ina: Dr. Michaelis, my mom was recently diagnosed with ET this week; she had a bone marrow biopsy. Maybe you’ve had one, Beth; I’ve had a bunch of them. And please advise why the bone marrow biopsy is needed and what we should expect to take place when we meet with the hem/onc next week to review the results.

Dr. Michaelis:

That’s an excellent question. Essential thrombocythemia can often be – you can suspect it on the basis of the peripheral blood, but you cannot confirm it and clearly know whether or not the condition is essential thrombocythemia or myelofibrosis without examining the bone marrow. So the recommendations, and your doctors followed the standard of care in diagnosis, is to perform a bone marrow biopsy at diagnosis for everyone suspected of having a myeloproliferative neoplasm. It used to be you didn’t need it for PV, but now that’s a part of the recommendations as well.

So, I think they did the right thing by doing the bone marrow biopsy. When you get together with your doctor, you should expect first off for them to clarify exactly what the diagnosis is, and what data has led them to that. The second thing you should ask them is what risks does this pose to my mom; what are the things we need to worry about? Does this make it more likely for her to have bleeding or blood clotting? Is there anything we need to do about that? Is there a reason why she needs to start treatment? And that treatment should be chosen or based on that risk stratification.

So I would say that your conversation should be about what data led to the diagnosis, how sure we are of that diagnosis, and whether or not her risk status require that she be considered for treatment.

Andrew:

Wow, great answer. That really gave me a lot of information. You mentioned Dr. Ruben Mesa, who we all know along the way. He’s going to be with us on a program we’re going to do in August.

So for all of our viewers today, be sure to be signed up with Patient Power so you get our email alerts, and you’ll be kept informed. There are a lot of programs coming up. There’s even an event that’s going to happen I think June 24th in Chicago. So we’re all plugged in. Dr. Michaelis has been with us a number of times; Erin has been with us before.

So we have this sort of community in the MPNs now. I think virtually now, more than ever before; you are not alone. Beth, you saw Esther and I on Facebook Live, you were telling me. We’re all connected, now and Beth is on a program. Beth, I want to wish you well with your PV, and we’ll have you on another program sometime. Thank you for joining us from Oxnard, north of LA today.

Dr. Michaelis:

Good luck, Beth. Thank you.

Beth:

Thank you both. Thank you.

Andrew:

And Erin, thank you for joining us from Levine Cancer Institute. Please tell Dr. Grunwald hi; give him a hug from me.

Erin:

I will be happy to.

Andrew:

Thank you for being with us once again, the MPN Hero.

Erin:

I was in good company.

Andrew:

Oh, thanks. Laura Michaelis from the Medical College of Wisconsin up there where you have either a lot of daylight or not much daylight in Wisconsin, thanks for being with us. And I know you have a cold; feel better, okay?

Dr. Michaelis:

Thank you very much. Thank you.

Andrew:

Okay. Well, we’ve had a great program. Remember, keep informed about our series. The Living Well series is really designed to keep plugging away at the different issues that we face as MPN patients and family members. I want to thank the Patient Empowerment network; this is really their program, produced by Patient Power. We also want to thank the Insight Corporation for their ongoing support.

In Carlsbad California where it’s sunny today, I hope it’s nice weather where you are. I’m Andrew Schorr, and as I like to say: remember, knowledge can be the best medicine of all.