Tag Archive for: spleen

Waldenström Macroglobulinemia Treatment Decisions: What’s Right for You?

Waldenström Macroglobulinemia Treatment Decisions: What’s Right for You? from Patient Empowerment Network on Vimeo.

What determines the best Waldenström macroglobulinemia treatment for YOU? In this 30-minute webinar, Dr. Jorge Castillo reviews key factors that affect treatment decisions, emerging treatment research, and shares tips for partnering with your healthcare team.

Dr. Jorge Castillo is Clinical Director at the Bing Center for Waldenström Macroglobulinemia Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School. Learn more about Dr. Castillo, here.

See More From The Pro-Active Waldenström Macroglobulinemia Patient Toolkit

Download Guide

Related Programs:

Waldenström Macroglobulinemia Patient First Office Visit Planner

Waldenström Macroglobulinemia Patient First Office Visit Planner

WM Patient Follow-Up Visit Planner

Waldenström Macroglobulinemia Patient Follow-Up Visit Planner 

Waldenström Macroglobulinemia Treatment Decisions: What’s Right For You? Resource Guide 



Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. In this program, we’re going to help you learn more about Waldenstrom macroglobulinemia, what it is, and how it’s treated, and we’ll share tools to help you work with your healthcare team to access the best care.

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Joining us today is Dr. Jorge Castillo. Dr. Castillo, welcome. Would you please introduce yourself?

Dr. Castillo:               

Yes, hi. Thank you, Katherine. My name is Jorge Castillo. I’m the clinical director of the Waldenstrom’s Program at the Dana Farber Cancer Institute in Boston.


Excellent. Thank you for taking the time to join us today.

Dr. Castillo:               

Happy to be here.


Before we get into the discussion, I’m sure this has been on the minds of many patients. Is the COVID vaccine safe and effective for Waldenstrom’s patients?

Dr. Castillo:               

Yeah, that’s a great question. I think the short answer is yes. We have a number of studies that not only our center but other centers in the United States and Europe have been doing. And we have seen that patients with Waldenstrom’s do benefit from the administration of the COVID vaccine.


Excellent. Let’s start with the very basic. What is Waldenstrom macroglobulinemia?

Dr. Castillo:               

Yeah, Waldenstrom’s macro – it’s a mouthful.


It is.

Dr. Castillo:               

I can just call it WM for ease.

It is a blood cancer, and in this blood cancer, the malignant cells are nesting in the bone marrow. And not only that. These malignant cells kind of secrete, produce, a protein called IgM.

IgM is an antibody that should be protecting us from infections, and in a normal state, we all have a little bit of IgM, and that’s a good thing. But in these patients, with these malignant cells, as these cells accumulate in the marrow, they actually increase the levels of IgM in our patients, and that can translate into a number of different symptoms, which we will probably talk about later.


Yes. How is it staged?

Dr. Castillo:               

So, the staging is a very interesting aspect. So, when we think about cancer, we think about stage I is in one spot, stage II in another spot, stage III, right, and it gets more extensive as we go along. That doesn’t really apply to Waldenstrom’s. Waldenstrom’s is a whole-body disease right from the start. The main reason for that is because it’s a disease of the bone marrow, and we all have bone marrow in all our bones, from our skull all the way to the great toe, so if you were to get a sample from each bone space, we would find the malignant cells there. So, this is a disease that is a whole-body disease right from the start, so therefore, there’s no stage I, II, or III. That is just the way we envision this.


How does the condition progress?

Dr. Castillo:               

So, it’s interesting because a number of the patients that we see in my clinic are actually asymptomatic at the time of the presentation. I would say maybe about a third of the patients I see in my clinic that were diagnosed with this disease for other reasons. They either had an abnormal laboratory value or an abnormal imaging study or some other reason. And when they come, they are worked up. Initially, they are found to have these malignant cells and these IgM elevation, but they have no other problems whatsoever.

So, I would say most patients will be asymptomatic at the beginning of the disease, and probably they will be asymptomatic for years before the symptoms actually do start. So, what happens is the malignant cells start taking over the bone marrow space, and it reaches a point in which the bone marrow, the healthy bone marrow, doesn’t have space to produce the normal cells that they should produce.

So, the first things that we tend to see in these patients is anemia, so the hemoglobin level starts dropping.

The red cells are the first ones that are being affected by this process so that the anemia is being seen first. If we leave that for a long time, then the other blood cells will decrease also, the white blood cells and the platelets over time. But the first one is almost always the anemia. And obviously, that, patients feel tired. They feel short of breath. They feel fatigued and all of that.

Now, the IgM itself can cause other problems on their own. If they have there’s too much IgM, they can actually make the blood a little thick, and that can cause a little bit of problems with the circulation, specifically in the eyes, for example. Some patients have blurred vision. Some patients have nosebleeds or headaches, right, with all that hyperviscosity, which means the blood is too thick. In some other patients, we have nerve damage. You know, they can have numbness in their toes, and then that increases into the – progresses, extends into the feet, into the shins, into the knees and then the fingers.

And so, that happens over years sometimes. Some patients can have enlargement of lymph nodes in their necks and in the axillary areas or in the inguinal areas, or even enlargement of organs, the spleen and liver and things like that. So, when we think about the clinical manifestations of Waldenstrom’s, it varies, very diverse. But I would say most patients would have anemia. I think that’s probably the most important aspect of it.


Thank you for that. That’s really helpful. So, now that we know more about Waldenstrom’s and how it progresses, let’s turn to treatment. Help us understand when it’s time to treat. Certain patients, as you said, don’t really need treatment right away because they’re asymptomatic. So, which patient type should begin to get treatment?

Dr. Castillo:               

That’s really the most important aspect of the discussion, I would say, because from my perspective – you know, I’ve been doing this for almost a decade, seeing probably 3,000, 4,000 patients with Waldenstrom’s in my career, I think one of the most important decisions is when to treat.

A number of our patients will be asymptomatic, and they will remain asymptomatic for years. So, really, treatment initiation in this scenario is not reasonable. Number one, we don’t cure the disease. Number two, patient have a long survival. I’m talking about 15, 20 years of survival in a large proportion of patients. So, a treatment that is going to last a year is not going to change a 20-year survival, so we don’t extend the survival of our patients in most cases.


Right. If a patient has been on watch and wait, how do you know when it’s time to begin therapy?

Dr. Castillo:               

Yeah, so essentially, when we see patients in whom we decide to monitor, right, watch and wait, which is monitor them, we follow them over time, and we see them sometimes every three months or every six months, and we get bloodwork.

We do bloodwork on those patients to look at the hemoglobin, just to see if there’s anemia or not, to look at the IgM to see if it gets too high or not. And if the IgM is too high, sometimes, we’ll have the patients have eye examinations on a yearly basis to make sure that there’s no changes in the vessels in the back of their eyes, in their retinas. That’s an indication of hyperviscosity. And every time we see them, not only do we look at the numbers, which I think is important, but we also look at the symptoms.

So, I classically ask my patients, “How’s your energy level, how well you’re doing, still able to do everything you want to do? Any numbness in your feet? Right? Any nosebleeds, any headaches, any blurred vision, right? Any lumps? So, I just go over this list of different symptoms that patients can experience. Are you having fevers? Are you having night sweats? Are you losing weight for no reason? Right? So, it’s a monitoring process.

Just to clarify further, for example, a patient can come to see me with anemia, and I know that Waldenstrom’s causes anemia, as I said before. But it is my duty as a doctor to make sure that there’s no other reason why the patient might be anemic. So, even though in the scenario, which is very likely that the disease is causing this problem, I still need to make sure that it is not something else driving this anemia for the patient, and then the anemia is severe enough. You know, some patients say, “Yeah, I’m a little tired, but I’m still able to do everything I want to do.”

So, really that’s a very minor process. And there are people who tell me, “You know what, I cannot play with my children anymore, right, because I’m so tired,” then that’s a different process. So, the severity of the symptom and how related to the disease it is, that combination is what really tells us who needs to be treated or not.

So, what I would say in terms of treatment timing for Waldenstrom’s patients, it’s not that you need treatment and then you don’t need it, and then you need it. It’s not like that. It’s more like you don’t need it; you don’t need it; and then it is reasonable to treat. And there is a period in which it’s reasonable to treat, and that period can last sometimes months to years. Some patients can decide to be treated a little earlier in the process with less symptoms. And some patients can decide to be treated a little bit later with more symptoms.

So, it has to do a lot with the patients, how they feel, how they’re tolerating the symptoms, how dangerous or potentially threatening those symptoms are. And that’s a conversation that it needs to take place between the doctor and the patient, understanding the patient’s preferences.


Yeah. Yeah. What are the treatment goals for Waldenstrom’s?

Dr. Castillo:               

So, as I said earlier, we don’t cure patients with Waldenstrom’s. Patients live with Waldenstrom’s, and I said before as well, for many years.

So, I think the goal of the treatment is to get back the patient – to get the patient back to how they were feeling before they became symptomatic. If the patient is not able to play with their children, as I said before, getting them back to play with their children again and have that energy. Or if they’re having all these lumps popping up in their bodies, kind of reduce the size of those lumps. Or if they’re having the neuropathy, have an improvement on the nerve ending damage and the numbness that they’re experiencing. If they’re having nosebleeds and headaches, resolve those symptoms.

So, in many other cancers, we think about complete remissions, cures, and that’s what we need to do. And we need to induce responses in our patients, and our treatments do induce responses in our patients, and responses are measured by IgM levels improvements and hemoglobin improvements and things like that, which is great to have the numbers improve, but I think it’s key to actually control the patient’s symptoms as well.

And I think it’s – from my perspective as a patient, if I were a patient, that would put it more important to me. So, what about my hemoglobin going from 10 to 13 if I’m not feeling better? So, I think feeling better is a very important aspect of what we do here.


Yeah, absolutely. Can you walk us through the currently available treatment approaches for WM?

Dr. Castillo:               

Oh, there’s plenty. And that is actually a good message. So, there are many treatment options, and the treatment options are almost equally effective. So, I think we can separate the treatment options in big groups. I think that the big group, the first group that we use, treatments that are very effective, is chemotherapy-based. And we have a number of chemotherapy options that we use routinely for patients with Waldenstrom’s. We typically combine chemotherapy with an antibody called rituximab. And that rituximab is used universally for a lot of different blood cancers out there.

And so, when we combine the chemotherapy with the rituximab, I would say probably 90 to 95 percent of patients that get treated do feel better. Not only their numbers improve, but also the symptoms improve, the treatments. These treatments are typically given intravenously, and they are typically given for about six months of treatments. It’s very easy to tolerate.

I mean, it’s not the classic chemotherapy that we think about with other cancers, right? Losing your hair and vomiting and being very sick. That is not what happens with these chemos. They are very gentle chemos. But the fact that they are gentle doesn’t mean that they do not work. I mean, they are very effective against the disease, but they are more gentle in terms of the side effects. Some other side effects that I think are important with chemo specifically is the small risk of developing another bone marrow disease, and that’s because of how chemo works. It also damages a little bit the good cells, and that can cause other problems, and the risk of infections.

I think nowadays, in the context of the pandemic, I think the risk of infections is something that we need to really talk about a lot with our patients. But these typically are six-month treatments, intravenous treatments, and then done with treatments and very effective regimens. Then, we have the non-chemo treatments, which is you have a lot of those, development of those therapies over the years.

We do have a group of medications called proteasome inhibitors, or PIs. And we borrow those from the myeloma group.

Myeloma is another blood cancer that shares some similarities with Waldenstrom’s, so we use some of those treatments into our treatments. And these are non-chemotherapy agents. We also combine them with rituximab to make them more powerful.

And some of them are intravenous. Some of them are injected under the skin. Some of them are pills. And again, six months of treatments, very nicely tolerated, very effective. I’m talking about 90, 95 percent efficacy rate. And the side effects with this are more like nerve ending damage or more like lung, heart problems, not really secondary malignancies, but infections is also an issue here too.

And then, we have the most – the newer treatments that are the pill form treatment. We call them BTK inhibitors, B as in Boy, T as in Tom, K, BTK inhibitors.

We use that for many other diseases as well, but we use them for Waldenstrom’s too. And we use them alone in most scenarios. Sometimes, we can combine them with rituximab, but the large experience is without rituximab. So, it’s just the pill. Nothing else. No injections or infusions. No risk of secondary bone marrow disease. No risk of neuropathy. But they are pills that you have to take every day, indefinitely.

So, in contrast with the other six-month treatments, duration treatments, these are treatments that tend to last for several years. And we do have some taking these pills sometimes for six, seven, eight years, and they continue on them because they do well, and their response is as good as chemotherapy. But it’s just with a pill that you need to take every day.

Now, these pills have a different set of side effects, and that includes sometimes some irregular heartbeats, some bleeding and bruising. We have a new pill just that we published on recently, a medication called venetoclax, with a V. Again, it’s a different mechanism of action. It’s a BCL-2 inhibitor. It doesn’t have any risk of arrhythmia or bleeding, but it can cause some issues with infections.

But maybe you can take two years of this treatment and not take it indefinitely. So, all these are treatments that we keep advancing, and we will continue running studies with new medications that hopefully have similar or higher efficacy with a better side effect profile.

Now, just to finalize, the last option that should always be in the mind of a patient is clinical trials, investigational agents that are not sometimes – some of them are approved already by the FDA.

Sometimes they’re not. But they are agents that either in the laboratory or in prior experience suggest that they might have efficacy on these patients.

And that’s another treatment option that could be considered in some scenarios.


Okay, excellent. Efficacy and many factors coming into play, obviously, when making a treatment decision. How do you decide which treatment is appropriate for a particular patient?

Dr. Castillo:               

Yeah, that’s a million-dollar question. And the reason that is the case is because when we think about other types of cancers, right, breast cancer and lung cancer, we do have these large studies with thousands of patients in which half of the group got one treatment; the other half got the other treatment. And we know that one treatment is better than other in this context of a randomized, large study. We don’t have a lot of that in Waldenstrom’s because it’s a rare disease. So, most of the studies that we do have are studies in which we have maybe 30, 40, 50 patients, 100 if we’re lucky, so comparisons between all these different treatments have not been done.

So, the chemotherapy, for example, versus the PI, there’s no study comparing that. The chemotherapy versus the BTK inhibitors, there’s no study comparing that. So, based on that, since there’s no comparison, we need to kind of understand the profile of the drug, you know. And you need to match that with the patient’s preferences.

So, we need to look at the patient’s age. We need to look at the patient’s comorbidities. We need to look at the patient’s medications that they’re on. Are their insurance going to cover the pills or not? Are they comfortable with getting intravenous infusions? What is the risk of leukemia versus the risk of neuropathy in those patients? So, we need to look at so many factors. Interestingly enough, efficacy is not the problem. We don’t choose treatments based on efficacy because all of the treatments are almost equally effective. We actually choose treatments based on patients’ preferences. We choose treatment based on the medication side effects.

And the newer thing is actually, we’re doing genomic profile in the patients. We’re actually seeing which mutations the patients have, and there are some treatments that work better or worse with specific mutations, so we kind of tailor a treatment option based on all those factors.

So, it’s not an easy job, but I think it’s rewarding to understand that the best treatment for a patient with Waldenstrom’s is a personalized treatment. And as long as –


That’s what it sounds like.

Dr. Castillo:               

And as long as the patient understands the best he or she can in terms of the pros and cons of the treatment before going in, an educated decision, I think that’s probably best choice, yeah.


Are there test results that can impact options?

Dr. Castillo:               

I would say so. So, for example, in patients who have very high IgM levels, we try to avoid giving rituximab alone, for example, because rituximab can also make the IgM go up in about 40 to 50 percent of the cases, and patients can become more symptomatic if they were symptomatic because of the IgM in the first place.

So, that’s one value that we follow carefully. Sometimes, the kidney function can tell us if there are some chemotherapies that cannot be given with a kidney function that is not normal or close to normal, for example. And again, there are some mutations that can help us understand if a treatment might work better than other treatments too.

So, yeah, there’s a lot of shades of gray in there to be able to pick and choose. And again, the patient’s symptoms are important. I mean, if a patient, for example, already has an arrhythmia, I’m going to try to avoid a medication that can cause more arrhythmias. If a patient has already some nerve damage, I’m less likely to recommend a treatment that can cause more nerve damage. So, yeah, there’s a lot of room there for personalization.


Yeah. You’ve mentioned existing conditions. So, how do patients’ specific factors like lifestyle and age and other preexisting conditions impact treatment choices?

Dr. Castillo:               

Well, I think the way that affects it is just because patients who are older age tend to have other problems, you know. And I think having that in mind is important. So, if somebody has a liver dysfunction of some kind, then that will modify my treatment options. And as I said earlier, if someone has a kidney disfunction of some kind or depending on the degree, I can choose a different type of treatment there.

Now, also, we need to be mindful, for example, if somebody’s not so reliable on taking pills because they cannot remember or they don’t know, they are not organized enough or they don’t – you know. So, there are so many other factors playing into that role – maybe a pill form treatment might not be the best option, you know.

If somebody doesn’t have help to transfer him to take him to the infusion room back and forth, maybe an infusion treatment might not be the best there. So, again, another series of factors could be taken into account when making treatment decisions.


There’s obviously so much to consider when choosing therapy. What do you feel is the patient’s role in treatment decisions?

Dr. Castillo:               

From my perspective, the patient’s role is very important. I need, as a physician, that the patient feels that it’s part of the team here. So, when patients come to see me, I strongly encourage patients to bring as many people as they want with them. If they want somebody on FaceTime at the same time, I’m happy with that too. And that helps because the amount of data that we provide, the amount of information that we provide, is a lot in terms of quantity. But sometimes, it’s not easy to understand when you just hear it one time, right?

So, having somebody taking notes, having somebody else taking notes, having somebody else listening, somebody else asking questions, and then somebody else explaining back to the patient – the patient is looking for the best for them, but if he’s also affected by the whole process. It would be naïve to feel – or to think – that somebody was told they have an incurable blood cancer, and they are completely paying attention to everything you’re saying, after you said something like that.

So, I think it’s important for patients to be there with family, friends, or whoever wants to be there to help out. I think that’s a really important aspect. Then, number two is you need to know about your own disease. And I am fortunate to work with a group of patients who are highly educated, to the point that they get to know more about their disease than their own doctor. And I think that’s key. I think that’s important. For me, that is not threatening or challenging. I think that is actually a good thing.

And that way, I can have a more direct conversation, meaningful, because I understand that the patient is understanding what I am saying, and we are trying to speak the same language, so I think that is key also. So, bottom line, I think education from the patient perspective, involvement of their care, I think that’s key so they can be their own best advocates.

There is going to be a lot of – since it’s a rare disease, there’s going to be a lot of backs and forths with different physicians. Some physicians are going to be more intensive and trying to treat when the patient doesn’t need to be treated. The opposite is also true in which a patient, they do need treatment, and the physicians are saying, “No, we can wait a little bit longer.” And again, that has nothing to do with the quality of the doctor. It’s just the fact that the disease is rare, and to keep up with it is very difficult. So, the patient being their best advocate is actually a very important role that they should have.


Knowledge is power.

Dr. Castillo:               

That’s right.


How is treatment effectiveness monitored? How do you know if it’s working?

Dr. Castillo:               

Yeah, so a couple of ways, right? We have the formal way and the informal way. So, the formal way to measure a response is, I mentioned before, the IgM. All right? So, the IgM levels, we use the IgM levels and how they decline over time on treatments to measure the response of the patients. So, based on the IgM decrease, we can actually classify the patients’ response in different depths.

So, we have minor responses, which is 25 to 50 percent decrease in the IgM, and then we have a partial response, which is a 50-90 percent decrease in the IgM, and then we have a very good partial response, which is a 90 percent decrease of the IgM or normalization of the IgM. So, it all depends. So, if your IgM let’s say, is 3,000, right, you will not be in a partial response unless your IgM is below 1,500, and you will not be on a very good response unless your IgM is below 300, for example. And that might be different for somebody who starts with an IgM of 10,000, and that might be different for somebody who start with an IgM of 500, right?

So, that’s the formal response criteria that we use, IgM-based. Having said that, we also have other factors in terms of the quality of life of the patient. So, we can see improvements in hemoglobin levels. We can actually see normalization of hemoglobin, even though the response to the IgM is minor. Right, you say “minor”, and I mean, how great that is?

But if the hemoglobin goes from 8 to 15 on a minor response, I think that patient is doing very well, right? So, we need to have those two hand-in-hand to understand what the benefit of the patient is seeing. If the patient is having hyperviscosity symptoms, for example, and the IgM was 6,000 and went down to 4,000, that’s enough for the patient to be without hyperviscosity symptoms. Then that’s a successful treatment too. So, we need to balance all that out and make sure that we understand it very well. So, yeah, we do have the formal IgM responses, but we do have the physical quality of life response that we should also pay attention to.


Fatigue seems to be very common among Waldenstrom’s patients. Here’s a question that we received before the program. Kasey asks, “Why do I feel so tired all the time? Is there anything that can be done about it?

Dr. Castillo:               

That’s a great question, and as I said before and basically kind of summarizing what I put together, I mean, there are many patients why a symptom with Waldenstrom’s could be fatigued. One of them is they could be anemic. The other one, they could have some hyperviscosity symptoms causing some fatigue, maybe some inflammation in the body because of the Waldenstrom’s, but maybe there are other reasons why patients can be fatigued.

And if you go out there in the streets and you start asking people, “Are you tired?” 80 percent of Americans are going to be tired. I’m not trying to minimize the symptoms of the patients. What I’m trying to say is we need to be very careful at understanding what the relation of the fatigue is with the disease. We need to be convinced that there is a relation there.

If that happened in my clinic – for example, a patient comes to see me, and they are fatigued; their hemoglobin is 14, which is normal; their IgM is about 1,000, which is not supposed to cause hyperviscosity. So, I do not know really in that context if the Waldenstrom’s is driving the fatigue or not.


Or if it’s something else.

Dr. Castillo:               

Exactly. So, we need to make sure that the patient doesn’t have any iron deficiency, that the patient doesn’t have any thyroid problems, that the testosterone problems are okay, that there’s no sleep disturbances, that there’s no depression. So, there’s so many different other things that we need to make sure are not there before we mount into that. Because if someone is fatigued with a hemoglobin of 8, which is very low, with my treatments, if I make that 8 14, I know the fatigue is going to get better. But if the patient is fatigued with a hemoglobin of 14, which I am not going to improve with my treatments, then how confident do I feel that I’m going to improve the patient’s quality of life with a potentially dangerous treatment?

So, we talked about already secondary leukemias, neuropathy, other problems that the patient can have with the treatments or because of the treatments.

So, we need to balance that out and understand that the potential benefit has to be higher than the potential risk, and that’s why the personalization comes into play. So, fatigue is a big issue, and we try to take a very systematic approach about that, you know, ruling out other conditions, making sure that we understand its relation with the disease before recommending treatment just for fatigue.


Yeah. This is one side effect that is so important for patients to share with their healthcare team, right?

Dr. Castillo:               

Oh, absolutely.


So that their healthcare team can know how to treat them.

Dr. Castillo:               

That’s right. And again, there are so many interventions that are not medications that could be done in these type of situations, right? Meditation, mindfulness. There are so many other approaches to try to help in these type of situations, changing a little bit sometimes the perspective, trying to be a little bit more on the positive thinking, right?

So, there are so many different ways outside of pharmacological approaches that we can use to try to improve our patients’ quality of life.


Yeah. Knowing that one has an incurable disease can be very stressful, right? Knowing that you have to live with this.

Dr. Castillo:               

That’s absolutely correct, and again, what I’ve seen happening in some of my patients is every little thing that happens to them, they do not know if it’s because of the disease or not.


Oh, yeah.

Dr. Castillo:               

“So, I have a twitch there. Oh, it’s due to Waldenstrom’s. Do I need to be treated because of that twitch?” And that, I understand it. Well, I try to understand it. I’m not in that same situation, so I cannot understand it completely. But I try to understand how if you don’t trust your body anymore, right? I mean, you have a disease, and you don’t trust your body anymore, then how you trust all these little symptoms here and there?

So, in my conversations with my patients, I discuss these things openly and that you’re going to have a lot of different symptoms here and there. Most of them probably are not going to be related to the disease, but if some of them are concerning enough to you in terms of your activities, in terms of eating, drinking, sleeping, social life, sexual life, you know, working life, then let me know, and then we will be happy to investigate those because anything can happen to anybody.

So, you can have other problems. Waldenstrom’s doesn’t protect you from anything, so, and it’s always important to discuss this with patients and pay attention to the patients, not dismiss their symptoms, think about them with them, talk about them with the patients to try to understand how these are affecting them.


Dr. Castillo, are there emerging approaches for treating Waldenstrom’s?

Dr. Castillo:               

Always. And that’s the beauty – that’s the second part of when we talked about clinical trials, right, we talked about clinical trials? Science continues, and we work very closely with an organization called the International Waldenstrom’s Foundation, and they support research all over the world for Waldenstrom’s.

So, their message is since the sun comes up until the sun comes down, there is someone, somewhere in the world working on Waldenstrom’s, and that’s true.

So, there’s a lot of science in the background, and that science helps us understand how the Waldenstrom’s cells behave, and therefore, we can then start targeting some things. That’s how BTK inhibitors came out. That’s how proteasome inhibitors came out. That’s how BCL-2 inhibitors came out. All these are the result of science, applied into the treatments. So, at my institution and many other institutions in the country and outside of the country, there are newer treatments being tried all the time.

We have now – we are looking into combining BTK inhibitors with other agents. Germany is doing a number of different studies. Canada is doing a number of different studies. We are doing some studies in the United States as well, combining chemotherapy and PIs with the BTK inhibitors. We’re doing a study in my institution combining BTK inhibitors with BCL-2 inhibitors. So, and the idea is to try to create a more powerful agent or regimen and hopefully maybe not give patients indefinite treatments, more like fixed duration treatments.

So, I think that’s where it’s coming. It’s coming maybe double, triple combinations, fixed duration treatments. That’s what is coming in terms of that aspect of the research. And then, we do have newer compounds coming out.

We do have now some concepts in what we call immunotherapy, right? We think about antibodies.

We think about bispecific T-cell engagers. CAR-T cells, so all that is actually up and coming in Waldenstrom’s. There are actual clinical trials being done today evaluating all those different treatments for patients with Waldenstrom’s.

So, I think the future is really bright. I’m really optimistic, to be honest with you about the treatment of patients with Waldenstrom’s. Obviously, what we need, what we want, is cure of the disease. And again, we can think about cure in two different ways. We can think about the classic definition of cure in which we treat patients, the disease goes away, you stop treatments, and the disease never comes back, right? That’s one way of looking at cure.

The other way of looking at cure is you treat the disease, the disease is in a remission, you continue treating the patient, and then the patient basically dies of other reasons, right? That is a functional cure. So, I think we’re closer to the latter, much more than the former, but the efforts to continue developing new treatments, it’s not stopping anytime soon.


No, because we’re always constantly moving forward, having to find new treatments, definitely. Well, Dr. Castillo, thank you so much for taking the time to join us today.

Dr. Castillo:               

It has been my pleasure. I mean, I always enjoy the opportunity to be able to communicate with patients about what I love doing.


Yeah. Thank you, and again, thank you to all of our partners.

To learn more about Waldenstrom macroglobulinemia and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.

What Are the Benefits of MPN Inhibitor Treatment?

What Are the Benefits of MPN Inhibitor Treatment? from Patient Empowerment Network on Vimeo.

MPN expert Dr. John Mascarenhas shares an overview of how inhibitor therapy works to treat myelofibrosis (MF) and the benefits of this type of treatment.

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

See More from INSIST! MPNs

Download Guide

Related Programs

An Overview of ET, PV and MF Treatment Options

An Overview of ET, PV and MF Treatment Options

Which Gene Mutations Impact Myelofibrosis Treatment Options?

Which Gene Mutations Impact Myelofibrosis Treatment Options?

What Are the Considerations When Choosing Myelofibrosis Therapy?

What Are the Considerations When Choosing Myelofibrosis Therapy?


Katherine Banwell:

Dr. Mascarenhas, what is inhibitor therapy and how does that work?

Dr. Mascarenhas:       

So, inhibitor therapy in general are usually oral drugs for the most part, small molecule inhibitors that are geared and usually specific but not totally specific because then they can have off-target effects, but geared to inhibiting usually an enzyme that is overactive or is contributing to the pathophysiology of the disease.

I think in MF, probably one of the best examples is a JAK2 inhibitor. So, there are a number of JAK2 inhibitors that have been in clinical testing. There are two that are approved, ruxolitinib and fedratinib which are excellent drugs in inhibiting JAK2 protein itself in the cells that could be either upregulated or hyperactive in the signaling pathway, and it quiets down a signaling pathway in the hematopoietic cells that leads to a lot of the manifestations of the disease, namely symptoms and spleen.

So, one of the clear benefits of JAK inhibitors that was established many years ago and reinforced by multiple drugs that are either approved or in late-stage testing is these drugs are excellent in improving the symptom burden in the patients and reducing their spleen. Unfortunately, as a class, we’ve not seen these drugs induce remissions or cure patients. So, there’s still interest in developing, obviously, non-JAK inhibitor therapies. But inhibitors in general are inhibiting proteins that are either inappropriately activated or part of a cascade of signaling molecules that are contributing to the disease.

And they are not chemotherapeutic, which might be an important point to make. In past days, we’ve relied heavily in hematologic malignancies in using chemotherapies which are nonspecific and just kill dividing cells whereas inhibitors typically are targeted, and in some sense, it’s personalized to the disease with toxicity profiles that are usually quite distinct from the traditional chemotherapies that we use.  


How Is MPN Treatment Effectiveness Monitored?

How Is MPN Treatment Effectiveness Monitored? from Patient Empowerment Network on Vimeo.

How is the effectiveness of MPN treatment determined? Dr. Naveen Pemmaraju describes key factors to monitor treatment effectiveness to ensure optimal patient care and to determine when it may be time to consider a change in therapy.

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

Related Programs

Why You Should Speak Up About MPN Symptoms and Treatment Side Effects

Expert Advice for Learning About Your MPNs Online

Expert Advice for Learning About Your MPNs Online

COVID-19 Vaccination: What Do Myelofibrosis Patients Need to Know

COVID-19 Vaccination: What Do Myelofibrosis Patients Need to Know?


Katherine Banwell:

Once on therapy, how is the disease monitored and how do you know if the treatment is working?

Dr. Pemmaraju:         

So, it differs from each disease, but let’s take polycythemia vera for a good example. So, let’s suppose you have polycythemia vera. I think there’s three markers here that you can check. One is the blood counts, right?

So, you want to make sure that the blood counts are controlled. New England Journal, five or six years ago now, our Italian colleagues published a very seminal paper which shows that the goal of therapy should be that the hematocrit should be below 45. So, that’s actually a very nice number to have. So, not just waiting for symptoms of the disease but keep the number low. And if you do that, that correlates with decreased cardiac events, thromboembolic events.

Number two, I think that, besides the blood count, the spleen. The spleen and liver size also is a nice surrogate for how the disease is doing. So, if that’s enlarging or getting out of control, that may be time to stop what you’re doing, reassess. The disease may be progressing to myelofibrosis, for example.

And then I think, lastly, the absence of stuff actually helps, too. So, the absence of major bleeding, the absence of blood clots, the absence of transformation to MF. I think if the quality of life is good, you’re decreasing blood clots and bleeding, you’re not going to a more advanced disease state, these are all wins for us with P vera.

Katherine Banwell:    

You touched on this briefly, but I’m wondering when a patient should consider changing treatments.

Dr. Pemmaraju:      

Yeah, changing treatments is more art than science, I would say. So, it does – that’s one of those that is kind of specific from patient to patient. In general, what we just talked about gives you that guidance. So, in polycythemia vera, since we brought that up earlier, uncontrolled blood counts despite maximum medication intervention, the phlebotomy requirement being untoward and impossible to keep up with, the spleen size growing out of control, the quality of life being impossible – these are some aspects to look into changing therapy and/or clinical trial.

But remember, it’s not a one-size-fits-all, right? So, some patients, the counts – some of these things may or may not actually play out. So, it has to be more of a gestalt, more of a total picture there.

How Does CLL Progress? Understanding the Stages of CLL

How Does CLL Progress? Understanding the Stages of CLL from Patient Empowerment Network on Vimeo.

What are the specific stages of chronic lymphocytic leukemia (CLL), and how does CLL progress? Dr. Matthew Davids details the stages of CLL and indications for when it’s time to treat the condition.

Dr. Matthew Davids is Director of Clinical Research in the Division of Lymphoma at Dana-Farber Cancer Institute. Learn more about Dr. Davids here.

See More from Engage CLL

Related Resources:


An Overview of CLL Treatment Types



Okay. So, how does CLL progress? When do you know when it’s time to treat?

Dr. Davids:

The stages of CLL involve the progression of the disease. When we first meet patients, often they only have cells circulating in the blood, and that’s called stage 0 disease. It’s one of the few cancers where there’s actually a Stage 0 before even Stage I, and the reason for that is that many patients can go for years on Stage 0 disease. But as the burden of the CLL cells begin to accumulate in the body they can start to collect in their lymph nodes, and the lymph nodes can start to swell up whether it’s in the neck or the armpits or elsewhere. That’s stage I disease.

They can accumulate in the spleen, which is an organ in the abdomen. It’s kind of a big filter for your bloodstream, and as the filter traps more of these lymphocytes the spleen can slowly enlarge over time. That’s stage II disease.

And then finally, the CLL cells can get into the bone marrow, which is like the factory for making your blood cells. And if the factory floor gets all gummed up with CLL cells it can’t make the normal red cells, that’s called anemia. Or it can’t make the normal platelet cells, that’s called thrombocytopenia. And when we start to see those more advanced stages III and IV of CLL, that usually does require treatment. And what the treatment does is it clears out the factory floor and it allows for the normal machinery to make the normal blood cells again. So, that’s one of the more common reasons why treatment is needed is due to anemia and low platelets. Second reason can be if the lymph nodes or spleen get so bulky that they’re uncomfortable or threatening organs internally. We want to treat before that becomes a real threat.

And then, the third thing that usually happens as the disease progresses, patients can develop some symptoms, what we call constitutional symptoms. These can be things like unintentional weight loss, drenching night sweats that are happening on a consistent basis, and those sorts of things. So, if that’s happening at the same time as these other factors are progressing, those would be reasons to treat.

And notice that one thing I did not say is the white blood cell count itself.

That’s a common misconception. Some people think that as the white blood cell count goes higher – and people use all different thresholds, 100, 200 – that by crossing that threshold you need to start treatment. And in fact, that’s not the case. We have many patients whose white blood cell count can get very high but then it can kind of level off and plateau for a period of several years, and as long as they don’t meet those other treatment indications, they don’t need to be treated just based on the white count alone.

MPN Treatment Decisions: Which Path is Best for You?

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

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

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

See More From the The Path to MPN Empowerment

Related Programs:

Essential Lab Tests for MPNs

Ready to Start an MPN Treatment? What You Need to Consider

An Expert Summary of Current MPN Treatment Options


Dr. Ruben Mesa:

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

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

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

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

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

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

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

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

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

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

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