Tag Archive for: stem cell transplant

Personalized Medicine for Myeloma Treatment | What Patients Should Know

Personalized Medicine for Myeloma Treatment | What Patients Should Know from Patient Empowerment Network on Vimeo.

What is personalized medicine, and how can myeloma patients access this type of care? Myeloma expert Dr. Omar Nadeem defines personalized medicine and shares how test results can impact myeloma care and treatment options.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

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Self-Advocacy in Myeloma Care | Advice From an Expert

Self-Advocacy in Myeloma Care | Advice From an Expert

Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023 

What Should Myeloma Patients Ask About Developing Research

What Should Myeloma Patients Ask About Developing Research?

Transcript:

Katherine:

Well, Dr. Nadeem, we’ve been hearing the term personalized medicine more frequently in recent years. How would you define personalized medicine for myeloma, and how can patients access this type of care?  

Dr. Nadeem:

Yeah, personalized medicine or precision medicine is a term that we’ve really sort of used for many oncologic conditions over the last decade or so. I would say, for multiple myeloma, in terms of identifying a target within the myeloma cell that’s unique to the patient. 

And then deploying a certain therapy to that patient because of that target is still lacking. We do have one example where patients have, for example, an 11;14 translocation, which we see in about 15 percent of myeloma patients.  

There’s an agent called venetoclax (Venclexta) that is very active against that particular cohort of patients, although that is still not approved to be used, but that’s one example where that agent specifically benefits that type of myeloma. Other than that, most of the therapies that we have benefit essentially everybody with myeloma, which is great, but it’s not so personalized.  

Where I would say there’s the most personalization happening now, at least in my practice, is looking at which types of therapies an individual patient may receive. What I mean by that is if somebody’s in an excellent response, with quadruplet-based induction therapy, I have a very real discussion with them about the pros and cons of stem cell transplant.  

We make those decisions in real time depending on how the patient doing, depending on how their response is.  

And then kind of deciding a whole kind of what are the kind of risks and benefits and what makes sense for that individual patient. Similarly, when you go on to maintenance therapy, maintenance therapy means that after you’ve gone through the initial phase of your myeloma therapy and the disease is under control, what type of therapy can we keep you on to keep it under control for as long as possible? Historically, that has been lenalidomide or Revlimid. Now we’re adding drugs such as daratumamab (Darzalex) and other agents to Revlimid to see if that can further prolong the response to that initial therapy.  

So, all those decisions are so individualized that you have to discuss with your provider what makes sense for you and what are the pros and cons of doing one approach versus the other.   

Katherine:

Well, if we’re talking about in-depth testing, how do the results of that testing affect treatment options? 

Dr. Nadeem:

So, right now we use conventional blood tests to get a sense of response in the vast majority of patients. That includes the serum protein electrophoresis and the serum free light chain assay.  

Most patients have detectable levels of these proteins, abnormal proteins in the blood at diagnosis and then you can follow them using a blood test. There’s a subset of patients that have disease only that shows up on scans. So, we then kind of incorporate some of those scans and then, also, utilize the bone marrow results both in the beginning and in subsequent analyses to kind of give a big-picture composite response assessment for that particular patient. Nowadays, there are also other tools that we’re using, such as MRD, or minimal residual disease.  

That is a test that is done on a bone marrow biopsy to determine, if you don’t have detectable protein in the blood, do you have myeloma cells present at the deepest level possible? And if you do versus if you don’t, trials have shown that there is a difference in terms of prognosis. Now, while that hasn’t fully been utilized yet to make treatment decisions in patients that are not on clinical trials, we do get prognostic information out of it, and nowadays, more and more of those trials are using these MRD tests to determine what to do with treatment.  

And I think that’s how it’s going to be in the future. So, having those extra tests available but, again, important to discuss with your provider what is the utility of this test. How are we going to use this information for your individual case to make some decisions? 

Evolving Myeloma Treatment Options | CAR T-Cell Therapy

Evolving Myeloma Treatment Options | CAR T-Cell Therapy from Patient Empowerment Network on Vimeo.

What is CAR T-cell therapy, and who is it right for? Dr. Omar Nadeem of Dana-Farber Cancer Institute discusses the role of this therapy in myeloma care and shares an update in ongoing CAR T-cell therapy clinical trial research.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

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Clinical Trials for Myeloma Treatment | Essential Information for Patients

Clinical Trials for Myeloma Treatment | Essential Information for Patients

Personalized Medicine for Myeloma Treatment | What Patients Should Know

Personalized Medicine for Myeloma Treatment | What Patients Should Know

What Should Myeloma Patients Ask About Developing Research

What Should Myeloma Patients Ask About Developing Research?

Transcript:

Katherine:

Well, I’d like to talk about some new and emerging therapies in myeloma, starting with CAR T-cell therapy. Can you talk about who this treatment option might be appropriate for?  

Dr. Nadeem:

So, yeah, just to kind of give folks background, CAR T-cell therapy is a form of immunotherapy, where we take out an individual’s T-cells and then re-program them, essentially, to recognize myeloma cells. Right now there’s two approved CAR-T products for multiple myeloma, both in the relapse refractory setting. It’s really for patients that have had four or more lines of therapy.  

So, that’s a lot of different combinations that we currently have available. Those therapies stop working before patients are actually eligible for CAR-T cells at the moment. Both of these CAR T-cell products have been gamechangers in terms of improving prognosis for patients.  

The good thing about CAR-T cells is that it is a one-and-done treatment. So, patients, when they go through that initial phase of therapy, they are then off therapy, although we are now starting to study certain therapies that we may administer after CAR-T cells to get them to last even longer than they currently do, but that’s still in, for example, that’s one of the clinical trials or many of the clinical trials that are currently ongoing now, to try to answer that question.  

So, a lot of patients can be eligible for CAR-T cells. They have to have the prerequisite amount of therapies. Again, there are some sort of baseline fitness characteristics that we look at for patient’s ability to tolerate it. But as a whole, I consider CAR T-cell therapy more broadly applicable to myeloma patients than compared to, let’s say, a stem cell transplant.  

Katherine:

How has this therapy revolutionized myeloma care? 

Dr. Nadeem:

Yeah, before the first approval, now a few years ago, in this space we didn’t really have anything like this to offer patients. So, many of the combinations and other compounds that were in clinical trials would have a response rate somewhere around, let’s say, 30 percent. So, 30 percent of patients may respond to that therapy in that space, and that may only last a few months, and that was considered successful not that long ago. Now, with CAR T-cell therapy and bispecific antibodies, these therapies are highly efficacious.  

You see response rates of 70 to 100 percent in some of these immunotherapies, and what that’s translating into is patient’s disease staying away for a year or two years, even three years in some of these clinical trials. And again, this is completely unprecedented compared to what we had before.  

Katherine:

I understand that there are a number of clinical trials for different types of CAR T, or even using it earlier in the disease. Can you share updates in CAR T-cell therapy research? 

Dr. Nadeem:

Yeah, so, exactly as you pointed out, there have been trials already, actually, that have been completed, Phase III studies looking at CAR T-cell therapies in earlier relapses.  So, patients that have had either one of two lines of therapy. 

Both our CAR-T therapies have been compared to standard of care in that space and have shown superiority, and this is something that we all have been kind of waiting for to see if you deploy it earlier, perhaps you’re going to see even greater benefit, and that seems to be the case in some of these trials, and now we’re awaiting, hopefully, approval of some of these CAR T-cell therapies to be administered earlier because in fifth line, it’s very different than treating patients in second or third line, which I think will really vastly improve our ability to deliver this therapy to many patients, as it can be quite challenging for patients that are in fifth line, to allow them to go through the process of CAR-T cells and then having them be administered.  

I was looking at it head-to-head with stem cell transplant, as I mentioned before, and this is in the context of quadruplet and induction therapy followed by either CAR-T cells or stem cell transplant, and then followed by maintenance therapy. So, really trying to see if I can overcome what we typically have achieved with stem cell transplantation.  

We also are doing some studies even before that. So, patients, again, in high-risk smoldering myeloma, which we know have an increased risk of developing newly diagnosed disease in the next few years, perhaps that could be the time where we can give some of these immunotherapies, and that’s some work that we have going on at our center. 

Clinical Trials for Myeloma Treatment | Essential Information for Patients

Clinical Trials for Myeloma Treatment | Essential Information for Patients from Patient Empowerment Network on Vimeo.

How do clinical trials advance treatment options for myeloma? Dr. Omar Nadeem discusses the important role of clinical trials in improving patient care, key questions to ask your care team about trial participation, and the benefits of seeing a myeloma specialist. 

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

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Next Generation Myeloma Treatment Options

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Personalized Medicine for Myeloma Treatment | What Patients Should Know

Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023 

Transcript:

Katherine:

I’d like to start with the importance of a patient’s healthcare team. What are the benefits to seeking care with a myeloma specialist, even if it’s just for a second opinion or a consult? 

Dr. Nadeem:

Yeah, so, myeloma is a little less than 2 percent of all cancers, and it’s the second most common blood cancer, so certainly not rare. With that being said, if you go to a general community practice, they don’t typically see too, too many patients with this disease. So, alongside that, we have so many different treatment options and combinations and these, as I mentioned, immune therapies.  

And other therapies that are only actually carried out at academic centers for now, such as stem cell transplants, and CAR T-cell therapy.  

I think it’s important to kind of meet with an academic provider just to get a sense of what the patient may be facing, both in that immediate time, but also in the future, because a lot of myeloma therapy is lifelong. And in that case, you do have to come up with a plan for your whole treatment in a way early. So, it’s important to kind of one: hear it from another person, and then two: really sort of figure out what the outlook would look like for the individual patient.  

With that being said, many of our myeloma regimens that are approved can very easily be given at the local provider, and that’s usually our preference, for patients to be treated closer to home. So, ultimately, this is another way for patients to get input about their treatment program, but also talk about the future.  

Katherine:

That makes sense. Specialists at academic medical centers are typically more involved in research and clinical trials. 

And patient participation is essential to advancing medicine. So, how do clinical trials impact myeloma care? 

Dr. Nadeem:

Well, everything that we have available today for myeloma therapy was once in a clinical trial. So, all these promising therapies usually start in early phase studies and move on to Phase II and Phase III studies, and then those are the ones that the FDA uses to approve a particular combination.  

So, it all depends on kind of where someone is in their disease course. It also kind of depends on what their preferences may be in terms of taking on something that is beyond standard of care. So, as part of any clinical trial in whatever phase it may be, whether its newly diagnosed multiple myeloma, even smoldering myeloma, which is one step before that, relapsed/refractory myeloma…  

At each step of the way, there are clinical trials that are there trying to improve upon what’s already out here, right? So, we are, despite all these amazing advances, unfortunately, the disease is still not curable for a vast majority of patients.  

In that case, how do we move to that cure, or how do we kind of advance the disease even beyond this? And a clinical trial is a way to do that.  

Katherine:

What type of patient is most appropriate for a clinical trial? 

Dr. Nadeem:

So, there are criteria that each clinical trial uses in terms of eligibility. Some of that has to do with the disease characteristic itself, kind of where somebody is in their disease course, but many times it’s also patients’ fitness, organ status in terms of kidney function, their blood count to some extent, heart function, etcetera. There are some sort of minimal prerequisite guidelines that we have to enroll patients in trials. So, it really, again, depends on where somebody is in their disease course and what they may be willing to take on beyond what may be offered to them as part of standard of care.  

Katherine:

What questions should patients be asking if they’re entrusted in participating in a clinical trial? 

Dr. Nadeem:

I think the important thing is to sort of first recognize what’s available to them as part of standard of care and then what the clinical trial is trying to answer.  

So, for example, if it’s newly diagnosed multiple myeloma, we now have quadruplet regimens that we give to patients at the time of their diagnosis, and then the next natural question for eligible patients that now comes up is whether they should do a stem cell transplant or not.  

And alongside that goes with all these advances in immune therapies, such as CAR T-cell therapies and bispecific antibodies. And there are now trials looking at those therapies and comparing them, for example, to stem cell transplant to try to answer the question “Can we get even beyond something like a stem cell transplant?”  

So, that’s one example of a trial where a patient may be interested in saying “Okay, well, a transplant may be my standard path, but what if I try to enroll in this study and get randomized, for example, to the CAR-T arm? Then, perhaps, I’m getting access to some of these therapies early and maybe that’s going to improve my outcomes.” 

Do AML Patients Receive Allo or Auto Stem Cell Transplant?

Do AML Patients Receive Allo or Auto Stem Cell Transplant? from Patient Empowerment Network on Vimeo.

What type of stem cell transplant do AML patients receive? Expert Dr. Sara Taveras Alam from UTHealth Houston explains stem cell transplant for AML care and advice to help patients locate a bone marrow donor match.

[ACT]IVATION Tip

“…encourage family members and friends to enlist on the national and international available donor registries. I believe that when a patient gets diagnosed with AML, everyone in their immediate circle wants to help, and I tend to see family members and friends offer their bone marrow for transplant purposes. The likelihood of a friend or a distant relative being a match is very low. We know that siblings may have a high chance of being a match, parents or kids may be a half-match by definition, so there’s a higher chance of some unrelated person on the registry being a match to the patient than a distant relative or friend.”

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Advancing Equity | Research Initiatives in AML Disparities Among Black and Latinx Populations

How Do AML Patients and Outcomes Differ by Population Groups?

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Transcript: 

Lisa Hatfield:

When you mention a stem cell transplant, are those allogeneic stem cell transplants where they receive a donor’s stem cells, or are they the autologous where you take some of their stem cells at a certain point and then give them back to the patient?

Dr. Sara Taveras Alam:

So for patients with acute leukemia who require a stem cell transplant, it is an allogeneic stem cell transplant, so it does have to be a transplant from a matched donor, and the first pool of possible donors tend to be the patient’s siblings. If they have brothers or sisters from the same mom and dad, those are the possible first-line donors and are tested to see if they’re a match to the patient, and second to that, then the transplant institutions look into a donor registry.

So my activation tip for that question is to encourage family members and friends to enlist on the national and international available donor registries. I believe that when a patient gets diagnosed with AML, everyone in their immediate circle wants to help, and I tend to see family members and friends offer their bone marrow for transplant purposes. The likelihood of a friend or a distant relative being a match is very low.

We know that siblings may have a high chance of being a match, parents or kids may be a half-match by definition, so there’s a higher chance of some unrelated person on the registry being a match to the patient than a distant relative or friend. However, we could always pay it forward, and if we encourage our friends and family to enlist on these registries, it is very beneficial for our population.

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How Is AML Care Impacted by Bone Marrow Biopsy Results? 

How Is AML Care Impacted by Bone Marrow Biopsy Results? from Patient Empowerment Network on Vimeo.

What is the impact of bone marrow biopsy results on AML care? Expert Dr. Sara Taveras Alam from UTHealth Houston shares how test results are weighed along with patient factors to set a treatment plan and discusses additional patient monitoring, relapse, and how treatment journeys may vary.

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Transcript: 

Lisa Hatfield:

Dr. Taveras, how does the information gathered from a bone marrow biopsy influence treatment decisions for AML care?

Dr. Sara Taveras Alam:

The information gathered from bone marrow biopsies is crucial to decide on the optimal treatment for our patients. We do take into consideration patient factors such as age, comorbidities, and fitness to decide on the treatment that the patient benefits from; however, they are leukemia specific factors, mainly the driving forces behind that leukemia and mutations that may prompt us to use one treatment or another,  so that initial diagnostic bone marrow biopsy is crucial to get the patient started on a treatment course, and then typically, three to four weeks after starting treatment, patients would require what is called a post-induction bone marrow biopsy, so that we can assess the response to treatment, so at that second biopsy, what we’re hoping to see is a patient in a remission, whereas the initial biopsy for an AML patient may have had more than 20 percent blasts or immature cancer cells of AML. 

Our goal is that at this end of induction, three to four weeks after starting chemo, the bone marrow shows less than 5 percent blasts, and then we would call that a morphologic remission. In addition, we would be obtaining the chromosome analysis and mutation testing again on those marrows after treatment, because we would love to achieve the highest response possible where we not only eliminate the bad cells, but we are eliminating the driving forces of these bad cells.

So in an ideal situation where our induction treatment does lead into a remission, AML patients still need to undergo what we call consolidation chemotherapy to maintain a remission. Unfortunately, we know that if we stop treatment, our patients with AML will relapse, and the maintenance treatments depending on the regimen, we may have a stop day at four months or six months, depending on the regimen used, and at different time points during the treatment, a bone marrow biopsy may be repeated.

I think the most crucial time for bone marrow biopsies are at the diagnosis and after induction, if we have achieved our goal to achieve remission, then the bone marrow biopsy may be repeated monthly, depending on the institution that the patient is going to.

However, that part is negotiable depending on the patient’s goals and wishes. If the patient were planned for a stem cell transplant because of the characteristics of their leukemia…if it’s a more aggressive type of acute myeloid leukemia, what we call intermediate or poor risk acute myeloid leukemia, a stem cell transplant is recommended, and before proceeding with a stem cell transplant, we must confirm that the patient continues to be in a remission, so that’s another crucial time point to repeat the bone marrow biopsy in addition to the beginning of induction, so they’re getting a diagnosis and the end of that first induction treatment.

The time points between those two are kind of negotiable, especially in patients that have a lot of trouble with the biopsies, but may be very beneficial to confirm that we are keeping the patient into remission and carry the prognosis of the patient.

Of course, if there’s any concern that there’s a relapse, that would be another reason to repeat a bone marrow biopsy, and while confirmed that there has been a relapse and see what characteristics of the AML has changed, and what treatment would be appropriate at that time frame. Once a patient has been in remission, completed their maintenance treatment potentially received a stem cell transplant if it was appropriate for them, usually patients are surveillance clinic followed up, and a bone marrow biopsy is advisable for their first few years, about every three months to confirm that we’re maintaining a remission and that no further action is needed.

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Evolving Myelofibrosis Treatment Options: What You Should Know

Evolving Myelofibrosis Treatment Options: What You Should Know from Patient Empowerment Network on Vimeo.

Myelofibrosis treatment and care is evolving quickly so it’s essential to understand your options and work with your healthcare team when making treatment decisions. In this webinar, Dr. Gaby Hobbs will discusses the latest updates in research and clinical trials, the role of new and emerging myelofibrosis therapies, and shares advice for accessing quality care.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask 

Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell. As patients collaborate on treatment decisions with their healthcare team, it’s important that they understand all of their options and how these options may be impacted by research developments. That’s why the Patient Empowerment Network created the Evolve Series, to arm you with the latest information and to help you feel empowered and confident during conversations about your care.  

In today’s program, we’re going to hear from an expert in the field about the evolving treatment landscape for myelofibrosis and discuss how you can play an active role in your care.  

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

Dr. Hobbs:

Hi, how are you? Thank you so much for inviting me today. My name is Gaby Hobbs. I’m the clinical director of the leukemia service at Mass General Hospital in Boston and the director of the MPN program at MGH as well. I conduct clinical trials as well as see patients with myeloproliferative neoplasms.  

Katherine:

Thank you so much for taking the time to join us today. We really appreciate it.  

Dr. Hobbs:

My pleasure.  

Katherine:

Before we get into our discussion, can you share with the audience how the field of myelofibrosis has changed over the course of your career? 

Dr. Hobbs:

Yeah, so it really has been a very exciting journey. So, when I was in medical school, I think that we basically had just discovered the JAK2 mutation.  

So, in the course of my own training and then my professional career, we’ve gone from myeloproliferative diseases being conditions where we really didn’t necessarily have a reason why people would get these conditions. Now not only do we know about the JAK2 mutation, but we know about many other mutations that patients can have. Then in 2011, the first JAK inhibitor was approved, ruxolitinib (Jakafi), and since then, three additional JAK inhibitors have now been approved, including pacritinib (Vonjo), fedratinib (Inrebic), and most recently, momelotinib (Ojjaara).  

So, the field has definitely advanced concretely in that regard. But we also just have much more information about how to diagnose these conditions and also how to treat them. Outside of the JAK inhibitors, we’re better at recognizing when patients need to go to get a bone marrow transplant. For example, and our outcomes with bone marrow transplantation have improved significantly. We also have many other treatment approaches that wouldn’t have existed before, and we also recognize that patients with MPNs live with a lot of symptoms. So, I think that we’re better at just the doctoring part of taking care of patients with MPN. So, definitely, the field has just really, really changed significantly in the last two decades. 

Katherine:

That sounds like it’s been a rapid change, really. There may be some confusion, Dr. Hobbs, among people wondering what is the difference between primary and secondary myelofibrosis? Could you describe the differences?  

Dr. Hobbs:

Sure. Great question. So, that term, primary and secondary, is actually used in medicine very frequently for the description of many conditions that are not that different. So, primary means a patient has myelofibrosis and did not have any myeloproliferative neoplasm, or MPN, before their diagnosis.  

So, they went to the doctor and the first diagnosis they received was a diagnosis of myelofibrosis. Now sometimes we suspect that a patient may have had another MPN previously, such as essential thrombocythemia or polycythemia vera, but they just weren’t diagnosed.   

What I mean by that is, you know, let’s say you meet a patient and you look through their chart and you see that five years ago or 10 years ago, they had really, really high platelets or very high red blood cell numbers. So, there you could say, well, you know, you were never diagnosed with ET or PV, but maybe you had that. So, you probably have secondary myelofibrosis, but the diagnosis, you know, that you come with to the doctor is myelofibrosis. So, secondary myelofibrosis means that you had an underlying condition before, meaning you were first diagnosed with one condition like PV, polycythemia vera, or ET, and then those conditions turned into myelofibrosis.  

And then we call that secondary myelofibrosis, meaning it is secondary to the primary condition, meaning ET or PV. One area of confusion that I’d like to be able to clarify also related to this is if a person has secondary myelofibrosis, they don’t have two myeloproliferative neoplasms or two conditions. It is one and the same. They just live on a spectrum and over time, they can turn into, one into the other. So, it’s not that you now have two diagnoses, it’s still the same condition, it’s just morphed a little.  

Katherine:

Okay, thank you for that explanation. I’d like to talk about the importance of a patient’s healthcare team. What are the benefits to seeking care with a myelofibrosis specialist, even if it’s just for a second opinion or a consultation? 

Dr. Hobbs:

Great question. I think that one thing that COVID has given us is the ability to have webinars like this, but also that you can seek second opinions more easily with the advent of telehealth.  

So, whereas before I think that getting that second opinion would have been maybe more challenging, perhaps now it’s easier. But to answer your question, these conditions are rare. Myelofibrosis in particular is even more rare than the others.  

The landscape, as I kind of alluded to in our initial question, has changed significantly in the last two decades. So, getting a second opinion, whether that’s, like you said, just for an initial consultation, and then you never see that person again. Or you end up having kind of two doctors, one that treats you for your day-to-day needs and an expert or specialist that sees you occasionally as things may change, which can be very beneficial for a variety of reasons. I think that the first one is to just hear hopefully the same information that your initial doctor gave you, but maybe from a different perspective. I think that’s always helpful when dealing with a new diagnosis.  

Second is, you know, a specialist may have access to clinical trials. Although that may not be the right thing for you when you first meet them, it may be something you would want to consider or may be appropriate for you later down in your treatment. So, being connected to somebody that has access to research is something that, you know, it opens a door.   

Katherine:

We’ve established that research in the field is moving quickly. What are new and emerging therapies that are showing promise?  

Dr. Hobbs:

Yeah, so the list is long and it’s getting longer. So, in addition to the fact that we now have four JAK inhibitors approved, which is worth just remembering that, because not that long ago we only had one, and one of them was just approved less than six months ago.  There are many new agents that are being studied in combination with the JAK inhibitors. This past year at the American Society of Hematology meeting, which is the annual meeting where we go to share our research and learn from our colleagues, there were two Phase III studies that were presented at the same time.  

I can’t remember, or I don’t think, but that has really ever happened before for myelofibrosis. One of them was with an agent called pelabresib, which is a type of molecule called a BET Inhibitor. And the other one was with an agent called navitoclax, which is an agent called a BCLXL-BCL2 inhibitor, which is a molecule that helps cells to undergo apoptosis or programmed cell death.  

So, these molecules were both combined with ruxolitinib. And we saw the results of the Phase III studies for each of these agents, and they were really quite exciting. The punchline for both of these studies is that they demonstrated that when you give two drugs as opposed to just one, the amount of patients that have a significant reduction in their spleen is doubled than when you give ruxolitinib in it by itself. So, for some of our patients that is a really meaningful number. You know, if you’re a patient that suffers from a big spleen, knowing that there’s a possibility of having two drugs that you can take to really shrink that spleen in a significant way, I think is very, very promising. On the symptom front, taking two medicines versus one medicine really didn’t seem to make a huge difference. I think we can analyze this in two different ways.  

We can see the negative or the positive side of this. So, on the negative side, well, it’s too bad that, you know, added medication didn’t help patients feel better. But on the upside, it’s also good that taking two medicines didn’t make people feel worse. Sometimes you can think of, you know, if you’re taking more medication, maybe you will feel worse. So, the jury is kind of still add on the significance of those results. But regardless, without getting into too much detail about these studies, I think it’s really exciting for myelofibrosis patients to know that there are two agents that are in Phase III testing.

That means that the next step is really consideration of FDA approval. So, when medications go through clinical trials, they go through earlier phase studies, Phase I, Phase II, and then finally they get to Phase III. A lot of work and effort has gone into these two compounds to try to get them to FDA approval. So, we’ll wait and see if in the next year or so we have new agents for the treatment of MF.  

In addition to these two, which of course are the most advanced, there really are a variety of other agents that are being tested. Those, for the most part, are still in Phase II testing. And similarly to the ones I mentioned before, most of the compounds, the way that they go into trials is first they start out showing that they’re safe by themselves, and then they get added to a JAK inhibitor.

So, far, because ruxolitinib has been the one that we’ve had around for the longest, most of these studies are being tested in combination with ruxolitinib. But we start to hear rumblings from clinical trials that perhaps some of the newer trials will consider using other JAK inhibitors as combination partners, which is a natural evolution. So, to name a few other agents, we have drugs like selinexor (Xpovio), and navtemadlin we have a PIM kinase inhibitor, a lysyl oxidase inhibitor, an LSD1 inhibitor, the list is long of all these different agents.  

Preliminarily, at least from the data we’ve seen from all of these compounds, I think there’s a lot of room for excitement. We see that combining these drugs together, the new agent plus the ruxolitinib, leads to a significant reduction in the spleen. And in some of these agents, we’re starting to see other endpoints. So, in addition to just looking at can we make patients feel better and can we shrink their spleens?

We’re starting to look at other things such as when we add these medications, do we see a reduction in the scarring or the fibrosis in the bone marrow? Do we see a decrease in the cells that have the mutation? Do we see the patients live longer? All of those things are endpoints in our studies that we really haven’t tested before. So, I think the field really will produce a lot of exciting data in the next couple of years.  

Katherine:

You mentioned clinical trials, and we will talk about those in a few moments, but are there innovations in technology that are accelerating myelofibrosis research?   

Dr. Hobbs:

So, the most obvious way to answer that question is simply that it’s much easier to diagnose myelofibrosis now, thanks to the ability to do genetic testing now much more easily than before. So, I think that previously, you know, getting JAK2 testing or testing for the other mutations was not as simple or would take a long time for the results to come back.  

Now, you know, I see even in the smallest of practices, ordering not just the JAK2 gene, but ordering what many of us do, which is like a panel of genes, where you test for a lot of the genes at the same time, has become almost commonplace. So, that’s really a meaningful advance in that it’s a technology that’s available and it’s no longer as prohibitively expensive as it was before.  

That doesn’t mean that some patients don’t end up getting charged in ways that doesn’t make any sense anymore, but that’s a conversation for another time. But I think just having the ability to make those diagnoses because of how easy it is now to test for these mutations is really very meaningful.

Outside of that, I mean, I would say that along with the improvement in the knowledge of what mutations patients have with myelofibrosis, we definitely have deeper ways of analyzing what genes are being expressed and in what cells they’re being expressed to really understand, you know, when do patients first get those mutations and how do those mutations change over time. So, we’re really diving deep into the actual biology of the bone marrow and there’s some studies that have demonstrated that patients may even have the JAK-2 mutation in utero, which is really, really fascinating. So, definitely a lot more understanding of the actual biology of how these diseases happen.  

Katherine:

Dr. Hobbs, a key part of research moving forward is the clinical trial process. Can you talk about the benefits of patient participation? 

Dr. Hobbs:

Yeah, so I think to answer that question, I should preface that by saying that I conduct clinical trials, and so certainly my answer is going to have that as a bias, so it’s important to know that. And I tell my patients that as well when I’m talking to them about clinical trials. Now, why do I think clinical trials are beneficial? Well, there’s really no way to advance the field without the sacrifice that patients do by allowing us to conduct clinical trials. Without clinical trials, we cannot get drugs approved. Without new drugs, we certainly can’t help our patients anymore with newer therapies. That being said, a clinical trial is something that is not just an experiment. Many times patients will be like, well, I don’t want to be a guinea pig. And I completely respect that.  

So, I think it’s really important to recognize too, that we take conducting clinical trials very, very seriously. The machinery that needs to exist in each hospital to conduct trials includes a ton of people. So, we have a lot of regulatory bodies, both within the hospital and outside of the hospital, to ensure that clinical trials are conducted in an ethical and in a safe way. So, one of the benefits, which you may not consider when you’re contemplating participating in a trial, is that your care team actually becomes much larger. You’re much more closely scrutinized actually, when you’re a member of a trial.

So, whereas before you would have just primarily seen me and my nurse practitioner, when you participate in a clinical trial, all of a sudden you have all these research nurses that are calling you, checking in with you, making sure you’re feeling well, et cetera. So, that’s actually a nice perk to participating in trials. So, an important thing to know with clinical trials is that they may not benefit everybody. 

And that not every clinical trial may be right for you and that there may be times when trials are appropriate and times where trials may not be appropriate. So, it’s not a decision that you make that’s black and white and that’s a decision that you make forever. I think it’s something that you can continue to discuss with your care team as you go through having this disease.  

Katherine:

Let’s move on to treatment. Would you provide an overview of the currently approved therapies for myelofibrosis?  

Dr. Hobbs:

Sure, absolutely. So, I’ve alluded to this a little bit. So, in 2011, we had the first JAK inhibitor approved called ruxolitinib, the brand name is Jakafi. After that, we had the approval of Inrebic or fedratinib and then pacritinib or VONJO, and then most recently momelotinib or Ojjaara. So, we have four different JAK inhibitors that are now approved for myelofibrosis.  

So, who needs to get a JAK inhibitor and how do we choose between the JAK inhibitors? So, the traditional indications for JAK inhibitors are, does a patient have bothersome symptoms from having a big spleen? Does a person have symptoms from their disease? Symptoms can include things like night sweats, itching, unintentional weight loss, brain fog, and fatigue. Fatigue can be challenging because of course many things can cause fatigue. But those are some of the symptoms that can occur with having this disease. So, if a patient has both splenomegaly symptoms or one or the other, they’re eligible for a JAK inhibitor.  

So, just having myelofibrosis doesn’t mean that you need to have a JAK inhibitor right away. Probably the most commonly used JAK inhibitor, and this will be the case probably for a long time, is ruxolitinib.  

The reason for that is that it’s been around for a long time, and it’s a very well-tolerated medication. Patients that have platelets that are very low, meaning platelets that are less than 50, should be considered for pacritinib first, as that’s the indication for that agent. Patients that don’t do that well on ruxolitinib initially, let’s say that the dose gets increased and the spleen and the symptoms are still present, but still have good blood counts, are good candidates for then receiving fedratinib. Fedratinib can also be given upfront. It rarely is given upfront, simply because ruxolitinib has been around for longer and it’s a better-tolerated medication. So, therefore most providers feel more comfortable giving that upfront. I have had some patients that are concerned about the weight gain that is a side effect of ruxolitinib. For those patients, I’ve occasionally considered giving fedratinib first before ruxolitinib. And then lastly, we have momelotinib. It’s approved primarily for patients with myelofibrosis and anemia.  

Now momelotinib is still a JAK inhibitor, so it can still improve symptoms, and it still improves spleen size. So, I struggle with that recommendation of just using it for anemia in patients that don’t have splenomegaly or symptoms.  

But the FDA label was pretty broad, and it’s important to recognize that. So, how is momelotinib being used? It can be used in the upfront setting for patients that have spleen and symptoms, and also anemia, meaning low red blood cell levels. Or,  it can be used for patients that have been treated with a JAK inhibitor first and then develop anemia. So, momelotinib is given to continue to improve the spleen and symptoms, but also help the anemia. So, that’s kind of like an overview of the four JAK inhibitors. Now we have a group of patients that maybe doesn’t have a lot of spleen symptoms or symptoms in general but has issues with having low hemoglobin. So, for those patients, we’ve used a variety of different medications, including medications that are called erythropoietin, which is a hormone that helps to boost the red blood cell levels.  

A medicine that’s similar to testosterone that can also help boost the red blood cell levels called danazol (Danocrine). And then there’s a medication called luspatercept-aamt (Reblozyl) that has been approved for a related condition called myelodysplastic syndrome. And in some clinics, it can be used even though it’s not approved either by itself or in combination with ruxolitinib. And then lastly, patients that have what is called high-risk myelofibrosis, meaning they have some mutations that may indicate that a patient has a higher risk of having complications of their disease, or they have very low blood counts, are usually considered high-risk. Those patients should be recommended and referred to transplantation as soon as they’re identified as having high-risk disease.  

Katherine:

When you say transplantation, you’re referring to stem cell transplant. 

Dr. Hobbs:

Yes, and I’m glad you said it that way actually. So, stem cell transplantation or bone marrow transplantation, same thing, interchangeable, same procedure. You got it.  

Katherine:

Yeah. So, where do clinical trials fit into a treatment plan? 

Dr. Hobbs:

So, it really depends on what is available at the site where you’re seeking care. Clinical trials come in a variety of different flavors. So, there may be a clinical trial for patients that are newly diagnosed, that are about to start a JAK inhibitor, for example.  

So, if you’re a patient that’s considering a JAK inhibitor to treat your spleen symptoms or your systemic symptoms, and there happens to be a clinical trial for adding on another medication, like the first JAK inhibitor you receive, well, that’s a great place to consider a clinical trial.  

There may also be clinical trials in later lines. Let’s say you were treated only with a JAK inhibitor first, but the study that’s available at your center is adding another medication to the JAK inhibitor if the JAK inhibitor by itself didn’t quite do the trick. 

There’s also other studies, for example, at the time of transplantation, for example, using the JAK inhibitors during transplant. So, really the clinical trials can be relevant at any time during treatment. In addition to clinical trials, testing new medications, there’s also other ways to participate in research throughout your time as a patient with your care team, which may include things like, for example, consenting to participate in a tissue bank.  

You donate a sample of your blood or bone marrow that is then later on used for research. Or we may have studies investigating the symptoms a patient has throughout their disease or their experience living with their disease. So, there’s many different ways of participating in research and clinical trials, even if those don’t necessarily include trying a new medication.  

Katherine:

What questions should patients be asking if they’re interested in learning more about clinical trials?  

Dr. Hobbs:

Yeah, great question. So, the first is understanding, you know, what is the medication that you will be receiving? Are you going to be receiving a placebo? Is that an option? This means a sugar pill. That’s a common question that I get. How do you get assigned to different groups? So, in one trial, there may be a group that gets one dose, another group that gets another dose, et cetera. So, it’d be important to know how are you going to get assigned and what are the options potentially for you before you sign up. After that, it’s important to know what phase the study is in.

So, is this a first-in-human study where your doctor may not be able to tell you a whole lot about what’s expected in terms of side effects or safety or toxicity? Or is this a Phase III study where maybe the trial has been open for many years and there’s been many patients that have been enrolled in it already? Or maybe this is a drug that’s already been approved for another condition and we’re borrowing it for myelofibrosis, for example, and then your care team can tell you lots of information about the safety and toxicities, etc.  

So, having a sense of where the drug is in its development, I think can be very helpful. Then there are some practical things that we sometimes do not spend enough time talking about.  

So, I’m glad to have the space to talk about that here. Participating in a clinical trial takes time. And it’ll take more time as a patient to participate in a clinical trial than to receive regular care. You may have to go to the hospital where you’re being treated more frequently. If you’re somebody that receives virtual care where some of your visits are telehealth and some of them are in person, you need to be aware that you may have more visits that are in person because the clinical trial procedure requires that certain labs or tests be done in the facility, not anywhere else. Clinical trials by definition, unfortunately, sometimes have to be very inflexible in order to ensure that we collect data in a uniform way.  

So, just being aware that it may take more time to participate is important. And along those lines, asking if the clinical trial will reimburse you for some of that time. So, for example, if you need to park in the expensive hospital parking more frequently, some trials will actually reimburse you for that. Or they may offer a hotel reimbursement if you need to travel from far away and spend a night there. So, don’t be afraid to ask those things because many times that’s built into the clinical trial.

So, that’s an important thing just practically to know. So, asking for a study calendar so you get a sense of how frequently you’ll need to be going to the doctor is really important. Also, then realizing that potentially you may have to go to see the doctor or the care team more frequently initially, but then after the first couple of months, if everything is going well, you’ll likely have the flexibility to go less often. So, all those questions are important to have in mind.  

Katherine:

That’s great information, thanks, Dr. Hobbs. When considering therapy, how do you approach a treatment plan for someone diagnosed with myelofibrosis?  

Dr. Hobbs:

Great question. So, when approaching how I care for a patient with myelofibrosis, I take several things into account. The first thing is, who is this patient? What other medical conditions do they have? How impacted are they by their myelofibrosis? Then what I like to do is to plug in the numbers of the patient, their blood work, their mutations, etcetera, into one of the many risk calculators that we have to determine what the risk of their myelofibrosis is. 

If a patient is considered high-risk, I will generally consider transplantation or discuss a referral to a bone marrow transplantation in one of our first visits, if not the first visit. After that, I need to determine whether or not the patient has symptoms from their disease, and if so, if they should receive a JAK inhibitor. Then I’ll look through their blood work, what their symptoms are to decide which JAK inhibitor to use first.  

If really the spleen and symptoms aren’t the primary issue, if it’s more related to low blood counts, then we can think about treatments directed at improving the hemoglobin, for example. There may be a group of patients that don’t actually require any treatment when I first meet them. So, just providing them with education, what to expect. Then discussing more of the psychological impact of living with a condition and approaches to handle that, maybe more the focus of my care.

And in general, for most of my patients, we also talk about the rest of the care. So, not just what the blood work is and what medicine I’m going to start them on, but also other things that they can do to take care of themselves, including making sure that they are actively monitored by their primary care doctor or by other specialists if that’s still appropriate. You know, one of the things we don’t discuss that frequently in myelofibrosis, we discuss that more often in essential thrombocythemia or polycythemia vera is a risk of blood clots.  

But the truth is that myelofibrosis patients can also have risks of blood clots. So, therefore, making sure that patients with MF that may have issues like hypertension, diabetes, high cholesterol, etc., get those well-managed is also really important to prevent them from having blood clots. So, lifestyle management is also an important part of the care of a patient with myelofibrosis. 

Katherine:

That’s all great advice. A note to our viewers, PEN has also created downloadable office visit planners to help you organize your thoughts and communicate effectively with your healthcare team. You can find those in the MPN Toolkit at powerfulpatients.org or by scanning the QR code on your screen.  

Well, it’s been a lot of great information, Dr. Hobbs, and I’d like to close with your thoughts on the future of myelofibrosis care. Where are we headed and what would you like to leave our audience with?   

Dr. Hobbs:

Well, the first thing I wanted to say is just kind of piggyback with what you said about the visit planner. I love that. I think that many times patients come to a visit and they’re like, oh, I had this question that I wanted to ask you and now I can’t remember what it was. And especially if you’re seeing a doctor every six months or something like that, making sure that you come to that visit prepared with lots of questions is an excellent way to make the most use out of your visit with your provider. So, I definitely encourage you to do that. In terms of what to leave patients with, so going back to what we were discussing initially, the list of new agents that are being investigated for myelofibrosis is long and longer by the day. So, as a myelofibrosis doctor, I really feel very optimistic that in  the next year and hopefully in the next couple of years, we’re going to have a variety of new treatment options that are going to really help our patients to live not just longer with their myelofibrosis, but truly to live much better with their myelofibrosis.  

So,  continue to get informed by watching webinars such as this one and reading reliable sources of information on different patient advocacy organizations because there’s really a lot of changes that are happening. So, I definitely think it’s a time to feel hopeful about the future of  myelofibrosis.  

Katherine:

Well, thank you so much for taking time to join us today, Dr. Hobbs, we really appreciate it.  

Dr. Hobbs:

Sure, it’s always a pleasure.  

Katherine:

And thank you to all of our collaborators. 

To learn more about myelofibrosis and to access tools to help you become a proactive patient, visit powerfulpatiens.org. I’m Katherine Banwell. Thanks for joining us.   

Expert Perspective | Disease Modification in Polycythemia Vera

Expert Perspective | Disease Modification in Polycythemia Vera from Patient Empowerment Network on Vimeo.

Is it possible to change the course of disease in polycythemia vera patients? MPN specialist and researcher Dr. Lucia Masarova shares an overview of the research in disease modification, discussing her work as the coauthor in an article entitled Moving Towards Disease Modification in Polycythemia Vera, recently published in the journal Blood.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova

 

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Transcript:

Katherine Banwell:

Dr. Masarova, you are a coauthor in an article entitled Moving Towards Disease Modification in Polycythemia Vera, which was recently published in the journal Blood. Can you share some of the highlights of the article and what it means for PV patients? 

Dr. Lucia Masarova:

Disease modification in polycythemia vera. I’m so excited finally being talking about this because we’ve been really, really, really so hungry for this term, although we still don’t know what it means.  

So, we group together with lots of experts in the myeloproliferative neoplasm field and try to brainstorm and put together, “What does it actually mean?” And to me, and to all of us, it was to offer our patients the normal or not-normal lifespan without the consequences of the disease that they face. Because we historically divided polycythemia vera into high-risk or low-risk disease based on the age or previous history of thrombosis or clotting complications.  

However, there is a huge area of patients that wouldn’t have either, and still suffer tremendously a bad quality of life, and ultimately also face the disease progression to myelofibrosis, which is the most actual complication of long-term polycythemia vera duration.  

So, the concept of disease modification would be to actually prevent the complications to even occur. To allow our patient to live free of having the fear of living with a thrombosis or clotting complication or ultimately progress into myelofibrosis. We have to learn how to get there. What are the relevant endpoints of tools for us to utilize to really understand? We have learned a lot from seeing what we call molecular remissions, or control of the JAK2 mutation with certain medications, for example, interferons or latest ruxolitinib (Jakafi), the JAK inhibition, where the decrease of the allele burden, which represents the disease, is correlated with better outcome.  

So, that is something that we have to be learning down the road with a longer follow-up. But that basically triggered us to focus on what can we do better? How do we prevent this from even happening rather than only controlling the historically main points of the disease which are presented by the blood counts symptoms and display? And where we are actually failing quite a lot of patients because despite them having a control count, they still don’t have a happy life, and lots of them suffer and complain.  

So, this is something to be learned, and this is opening the disease modification not only for polycythemia vera, but also for all patients with myeloproliferative neoplasms, which have a little bit of a different feeling in the whole myeloid malignancies field. Because it is a very long disease, and it could evolve and change, and only now we starting to understand what does actually happen there. Why some people could live for 30 years, and never face any consequences, and the others would progress very fast? 

So, disease modification would normally allow us to develop and learn more tools and better biomarkers, but also focus on drugs that are really needed to help with these long-term outcomes of our patients.  

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask from Patient Empowerment Network on Vimeo.

When considering therapy for myelofibrosis, where do you start? Dr. Lucia Masarova shares advice and key questions to ask your provider when making myelofibrosis treatment decisions.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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Transcript:

Katherine Banwell:

When considering treatment options, what key questions should patients ask about their proposed treatment plan? 

Dr. Lucia Masarova:

What’s the goal of my therapy? That is one of the most important things to know. Patients don’t even know how long they have to be on the medicines. What to do and how does it look when the medicine is still working? What do I need to be looking for in this medicine? And then what are we going to do if it fails? And what does it actually mean when it fails? What is the schedule? How burdensome the treatment is? How often do I have to come?  

How often and what do I have to pay? Because the financial burden we have to really, really face the truth. It is very, very, very significant and somebody living with this disease predicates. It’s something we cannot take lightly, and we really have to combine our efforts and help with that. There are fantastic patient support organizations, but is not well-known, and is still in the rare – in rarer field. So, there’s more effort that we do. 

When do I need more help? Where to be referred to more experts? What is the role of stem cell transplantations, if ever? So, those are really the key things.  

Where do I find reliable resources to learn about my treatment, to learn about the disease? How do I connect with people from the same community? It is a disease with a lower age in a lot of circumstances and really facing this disease in the 30s or 40s or 50s is a really challenging thing. Although we have more and more medications currently, we really do have now to start thinking about their durability, about the safety for long-term, about their assessments for not performing, and where do we place the ultimate cure for stem cell transplants?  

And how do we make it actually happen in more and more eligible patients? Because we have to face the truth. It is still not utilized to where it belongs. Patients are not being referred. 

Patients are not being transplanted. And they may change with novel therapies. But we have to really consider all of our tools to offer the longest life span and to prevent all the disease trouble that comes with living with MPNs.   

Katherine Banwell:

When it comes to clinical trials, where do they fit in in choosing treatment? 

Dr. Lucia Masarova:

For me, it’s number one., and always number one.  

That’s just the academic centers which are dedicated and focused on developing better and novel and up front and just tailored and customized drugs. But I know that the life is out there and it’s a little bit more challenging for everybody to deal with such a rare disease.  

I would definitely say any patient that does not respond to current therapy in terms of uncontrolled symptoms or spleen, or other concerns should be referred and evaluated for participation in clinical trials. It is the only way we could understand what is driving that this is not responding and how could we help the best?   

For patients with myelofibrosis, which is the most aggressive myeloproliferative neoplasm, I would definitely put it in. If they are not doing well on number  one, JAK inhibitor, whatever is being used, they should be highly encouraged to be referred to centers and evaluated for clinical trials. 

We have been developing as others and own strategies to potentiate the benefit and efficacy of the current treatments, as well as agents in what we call salvage or refractory setting.  

However, I cannot emphasize enough to really focus on the first track that providers choose for their patients and utilize it to the best ability to avoid frequent or quick switching. Because in a salvage or  refractory setting we cannot offer the same benefit we could offer upfront. We are pushing the disease, maybe being less responsive, maybe more refractory, if we don’t handle the medication we have currently on the table to the best ability.  

Those are excellent medications, fantastic drugs, but there are shortcomings in each and every one of them. And we could do better to really start thinking about what has happened with the medication, why is it failing the patient, and what else could we do? And that’s only possible in the clinical trial setting, especially in such a rare disease as myeloproliferative neoplasms are.   

Katherine Banwell:

Why is it important for patients to feel like they have a voice in their treatment options? 

Dr. Lucia Masarova:

Because it’s about the patients. I would say, as I always say to my patients, “Nobody’s a better advocate for you than you.” I really, really, really like working with patients. They are educated. They understand where to find resources. They’re not afraid to ask. That challenges all of my team and everybody to really be engaged. They know when to notify me. Not to be quiet when they need something. And really raise their voice when something doesn’t work.  

Patients know their bodies more than anybody can. And no data, no boxes, no books can ever tell me how it actually is. It’s not by chance we have two ears to listen and one mouth to talk.  

So, we have to really listen what the patient has to say and take all the abilities, the resources, the knowledge, the capabilities to really make the best thing for the patients, because it is ultimately and only about that.  

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis? from Patient Empowerment Network on Vimeo.

Is there a cure for myelofibrosis? Dr. Lucia Masarova explains the role of stem cell transplant for the treatment of myelofibrosis and reviews additional therapies for patients who do not qualify for the procedure, such as JAK inhibitor therapy.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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Transcript:

Katherine Banwell:

Dr. Masarova, stem cell transplant is sometimes recommended for people with myelofibrosis. Is this still the closest option to cure for those patients? 

Dr. Lucia Masarova:

I would say so, as much as we don’t like it. We would like to develop novel conservative, less aggressive, that we call procedures or drugs. Stem cell transplants still represent a long-term cure for patients that are eligible. 

Katherine Banwell:

What about for patients who don’t qualify for stem cell transplant? What are effective long-term treatments for them? 

Dr. Lucia Masarova:

That’s a very, very important question and topic. The key point here is the long-term because long-term is a little difficult term in conservative management of myeloproliferative neoplasm, particularly when it comes to myelofibrosis.  

With the development of JAK inhibitors, the longest experiences we have with the first one called ruxolitinib or Jakafi, we have seen prolonged outcomes in survival so patients could live longer than expected before.  

However, it’s not forever. So, that’s why we are trying to develop novel strategies where I see a lot of roles of combinations of JAK inhibitors and other correlative compounds, such as bromodomains inhibitors or hypomethylating agents or others that would affect the pathways that we are missing currently to cover with the JAK inhibition. And that ultimately leads to medication failures and patients being refractory and then having a shortened lifespan.  

So, I’m hoping we will develop something for long-term. Particularly promising a very, very interesting concept is with the calreticulin where we are developing monoclonal antibodies or vaccines because we have seen and discovered calreticulin driver to be a targetable thing that causes immunogenicity. 

But I do really hope that we will move forward with these discoveries and the JAK mutate or other drivers causing myeloproliferative neoplasms to offer long-term management.  

Understanding the Basics of CAR T-Cell Therapy

Understanding the Basics of CAR T-Cell Therapy from Patient Empowerment Network on Vimeo.

CAR T-cell therapy is an exciting new option to treat multiple myeloma, but what patient type is this therapy right for? Expert Dr. Shambavi Richard defines CAR T-cell therapy and explains the eligibility requirements.

Dr. Shambavi Richard is Co-Lead Physician for the Myeloma CAR-T Programs at Mount Sinai Tisch Cancer Center. Learn more about Dr. Richard.

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CAR T-Cell Therapy | How Can Care Partners Provide Support

Transcript:

Katherine:

Let’s begin with the basics of CAR T-cell therapy. What is it? And maybe, actually, we could start with what CAR is short for.  

Dr. Richard:

So, CAR stands for chimeric antigen receptors, so CAR T cell is a chimeric antigen receptor T-cell therapy. What that means is T cells, which is one of the cells for immune system are actually come from the patient. They’re expanded and activated in a manufacturing facility. And there they undergo genetic modification to form the CAR T cells. And what’s special about the CAR T cells is that they have the capacity to recognize myeloma cells and are efficient killers of the myeloma cells.  

Katherine:

Who might this approach be right for? What determines eligibility? 

Dr. Richard:

So, interestingly enough, today as we speak, CAR T cells may be eligible for many, many different kinds of – in the phases, many different phases of the myeloma journey. When they were initially tested, as most new therapies are, they were tested on patients who had very advanced myeloma, really were not candidates or did not have great options for any other kinds of therapy. And when they got tested in these groups of patients, they really had stellar results that far outstripped anything else that we had as options for patients in those advanced stages of myeloma.

So, the approval for CAR T cells as they stand today for myeloma is for advanced myeloma with patients who have had four or more lines of therapy and have had exposure to pretty much the major three classes of therapies for myeloma which includes proteasome inhibitors, imides, and anti-CD38 antibody therapy.  

But having said that, now CAR T cells are being moved into earlier lines of therapy are now being tested in these in various clinical trials. And even for newly diagnosed myeloma patients to see if they are as good as autologous transplants. Are they better than autologous transplants? And so on and so forth. So, really that’s what I mean by saying for now CAR T cells are appropriate for anyone if they are candidates for clinical trials. But in terms of approved indications for CAR T therapy, those are for advanced myeloma patients who have had at least four lines of therapy. 

Does CLL Research Show Potential for a Cure?

Does CLL Research Show Potential for a Cure? from Patient Empowerment Network on Vimeo.

Could chronic lymphocytic leukemia (CLL) research potentially bring a cure for patients? Dr. Danielle Brander shares her perspective about the future of CLL care, functional cure, and cure-like condition.

Dr. Danielle Brander is an Assistant Professor in the Division of Hematologic Malignancies & Cellular Therapy at Duke University Medical Center. Learn more about Dr. Danielle Brander.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

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Chronic Lymphocytic Leukemia Research and EVOLVE Trial Updates

Chronic Lymphocytic Leukemia Research and EVOLVE Trial Updates

Common Chronic Lymphocytic Leukemia Symptoms and Follow-Up Tests

Common Chronic Lymphocytic Leukemia Symptoms and Follow-Up Tests


Transcript:

Lisa Hatfield:

So as a cancer patient, one of the biggest questions I had when I was diagnosed, you hear the word “cancer” or in this case “CLL leukemia.” Two questions. One of them, is there a cure for CLL? And if not, are there any trials looking at a cure for CLL?

Dr. Danielle Brander:

Yes. Excellent. An understandable question. Traditionally, we say that CLL or others slower-growing, or sometimes you’ll hear the term indolent lymphomas, do tend to be slower-growing.  Some patients don’t need treatment. But the flip side of that is we generally think of them as not curable, that they’re a chronic condition and that treatment, the goal of treatment is to knock it down and relieve whatever symptoms or indications or reasons your starting treatment are.

But at some level, we historically think of CLL as either eventually coming back or sticking around, so to speak. However, I think most oncologists, most those in the field, feel that some of the treatments that are around or in combination, that we’re going to have some patients that have maybe what a term might be functional cure or individual, cure-like condition.

Meaning if our newer treatments for some patients can knock down the CLL so much that it either doesn’t come back or take so long to even show itself again, in a way that serves as what the purpose of cure, really is, which is to get it down to levels that it’s not causing problems or not coming back, for the lifetime of the patient.

Bone marrow transplant is the only therapy historically that has been cured, has offered a cure for some patients. The downside and the reason that most patients aren’t referred to for bone marrow transplant is the risk side of it. Meaning, unfortunately, a bone marrow or stem cell transplant has such a high risk of directly causing side effects.

That could be life-limiting or chronic side effects from the transplant itself versus the agents available now that we aren’t using or referring to bone marrow transplant nearly as much, but I think it’s really encouraging what we’re seeing in responses. So we talked already about those main categories of BTK inhibitors or venetoclax, I didn’t yet talk about, but there are many trials that have looked at those in combination, or CAR T, for example, or bispecific antibodies that are knocking down the CLL to such low levels. But the hope is that serves as a way of functional cure. But it’s going to take time to see if that’s the case. But we’re all very encouraged and really believe that that’s on the horizon.


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Stem Cell Transplant for AML | What Patients Should Know

Stem Cell Transplant for AML | What Patients Should Know from Patient Empowerment Network on Vimeo.

When is stem cell transplant an option for AML care? AML specialist Dr. Alice Mims discusses who this procedure is most appropriate for and how patients are monitored after transplant. Dr. Mims also addresses common issues following stem cell transplant, including joint pain. 

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims

See More from Thrive AML

Related Resources:

How Can You Thrive With AML Advice for Navigating Care.

Thriving With AML Tips and Support for Navigating Treatment

Thriving With AML | Tips and Support for Navigating Treatment 


Transcript:

Katherine Banwell:

Janet wants to know what factors enable a patient to achieve and continue in remission if they are not able to achieve stem cell transplant due to age restrictions.  

Dr. Alice Mims:

So, I think first and foremost, I think it’s very important that there — that patients are aware that there shouldn’t be just strict, stringent cutoffs of age as a requirement for stem cell transplant.  

 And really, there’s a lot of research going on that we should take into account. Physiological age, and there are ways to measure that just to be sure that stem cell transplant really is not an option. And for patients who stem cell transplant is not an option, I think as we talked about earlier, so there can still be really great treatments that can get patients into remission and ongoing therapies with dosing adjustments again to decrease toxicity and improve quality of life and thinking about things like maintenance therapy as appropriate. 

Katherine Banwell:

What are the age restrictions, and why are they there? 

Dr. Alice Mims:

So, sometimes you will hear age 75. Really, no one above age 75 should move forward with transplant. And that’s based off of past data where they’ve explored transplant and seen increased toxicity. And from transplant in itself, increased side effects, increased risk of early mortality. And so, I do think it’s important to take the patient as a whole into consideration because again, you could have someone who’s 77 who may be running marathons, and in great shape, and not a lot of other healthcare issues, who may still do really well with treatment. And so, I think that’s – really needs to be taken in account, really the overall picture of health for the patient before making…  

Katherine Banwell:

So, the… 

Dr. Alice Mims:

…just a firm cutoff. 

Katherine Banwell:

Right. Okay. So, it’s not cut and dry. 

Dr. Alice Mims:

Exactly.  

Katherine Banwell:

If you’re 75 or older, then you definitely can’t have stem cell transplant. 

Dr. Alice Mims:

That’s correct. 

Katherine Banwell:

Then you’re looking at everyone individually. 

Dr. Alice Mims:

Yeah. So, it really should be looked at. And I still have some patients who will come to me and say, “Oh, I was told I’m 68 years old, I’m not a candidate.” And that always makes me take a step back. And then we kind of have to have that discussion again. And they may still not be a good candidate based off of other comorbidities or healthcare issues, but it shouldn’t just be a number rules you out for having that as an option. 

Katherine Banwell:

Good to know. We received this question from Carl, “What does treatment look like following transplant? And what are doctors looking for when monitoring through blood tests?”  

Dr. Alice Mims:

Sure. So, after transplant, the first three months is pretty intensive of being seen very frequently at your transplant center twice to once a week. You’re also on immunosuppressive medications to try to help prevent issues like graft-versus-host disease, which can be a complication from transplant. 

And then over time if you’re doing well, we try to start tapering off those immunosuppressive regimens to see if you can tolerate that. And what I say to most of my patients for – who are undergoing transplant, it can take some time to really feel back to being yourself. It can take six months, it can take a year or longer. And sometimes your normal is a new normal based off of how you do and the side effects of the transplant in itself. So, you may not go back to if you’re here before transplant and before your diagnosis, it may be that this is your new normal. Just so people can be prepared and know what they’re signing up for.  

Katherine Banwell:

And with the blood testing, what are you looking for when you’re monitoring a patient? 

Dr. Alice Mims:

Sure. There are a few different things that we’re looking for when monitoring patients. So, one, making sure that the stem cells or the graft from the donor are recovering. 

You want to see that blood counts, levels of white blood cells, red blood cells, platelets are getting to normal levels. You’re also assessing and making sure you’re not seeing signs of relapse. You’re checking levels of donor cells versus the patient cells within the stem cell — sorry, within the stem cell compartments. And so, we’re taking all of those into account as well as checking organ function and making sure there’s no signs of potential graft-versus-host disease as well.  

Katherine Banwell:

Ryan wants to know, “I’m a year-and-a-half post-transplant, how can you tell if the aches and pains in your joints are normal aging, host versusgraft disease, the AML returning, or even something else?” 

Dr. Alice Mims:

So, I think that’s also a difficult question to answer, because it really is patient-dependent. And so, I think if you’re having new joint aches or pains, it’s always important to reach out to your transplant team to make sure that – it could be any of the above. 

And so you’re doing the appropriate workup with lab work, imaging, things that would be appropriate, or seeing certain specialists. Maybe orthopedist if needed because it could be I’d say less likely leukemic relapse, but still want to be sure. But it could be definitely complications from GVHD, or there are some joint issues that can evolve post-transplant, especially for people who are on long-term immunosuppressant medications. Or it could be the normal effects of aging. So, it’s always good to have that reassurance.  

Expert Advice | Managing AML Symptoms and Treatment Side Effects

Expert Advice | Managing AML Symptoms and Treatment Side Effects from Patient Empowerment Network on Vimeo.

The symptoms of acute myeloid leukemia (AML), or side effects of treatment, can have an impact on daily life. Dr. Alice Mims, an AML specialist, discusses how common issues are treated and talks about why it’s important to share what you’re going through with your healthcare team. 

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims

See More from Thrive AML

Related Resources:

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Thriving With AML | Advice for Setting Goals and Making Treatment Decisions

Understanding AML Treatment Categories

Understanding AML Treatment Categories 


Transcript:

Katherine Banwell:

When it comes to living and thriving with AML, Dr. Mims, managing disease symptoms and treatment side effects is a big part of that. 

Would you talk about how symptoms and side effects can impact life with AML? 

Dr. Alice Mims:

Sure. So, I think from my perspective, what we are always trying to do when we’re moving forward with a treatment plan is of course, get patients into remission, but the purpose of getting into remission is not just to achieve that, but for patients to have quality of life. And so, there needs to be continued dialogue between the patient and the treatment team about how you’re feeling during treatment. Because they’re definitely based off of therapy, different side effects, things that could be not necessarily due to active leukemia anymore. And so there may need to be dose adjustments and other things that we do to the regimens in order to make you feel as good as possible while continuing on treatment. 

Katherine Banwell:

Why is it so important for patients to speak up about any issues they may be having? 

Dr. Alice Mims:

I think it’s important because you’re your own best advocate. Being the patient, being the person who’s living with having this diagnosis and going through the treatment, myself, or other colleagues as physicians, we can have a sense of what may be going on based off of numbers. But we’re not truly going to know how you’re feeling unless you speak up and let us know. And there may be things we could do with supportive medications, dosing adjustments as mentioned, that could help in making you hopefully feel better and less side effects and toxicities from treatment. 

Katherine Banwell:

What are some common symptoms and side effects that you hear about?  

Dr. Alice Mims:

Okay. Sure. So, different side effects that I would say that people can have, people can feel fatigued just from treatment in general. Some of our therapies can cause neuropathy, skin rashes, nausea, vomiting, diarrhea. And so, all of those are important along as mentioned with symptoms you may have from decreased blood counts that we do have interventions that we could implement to help the – make the therapy more tolerable. 

Katherine Banwell:

So, for the side effects like fatigue, for example, what do you do about that? 

Dr. Alice Mims:

So, I think it depends on the level of fatigue. Of course, we don’t have – I wish we had a pill that could just make fatigue improve. But if it’s really that the treatment is deriving it, and it’s impacting your quality of life, there are dose reductions or things we can do that may help with the level of fatigue you’re experiencing.  

Katherine Banwell:

And what about some of the other side effects. You mentioned diarrhea. 

Dr. Alice Mims:

Sure. 

Katherine Banwell:

How is that handled? 

Dr. Alice Mims:

Yeah. So, for issues from GI complications such as nausea, vomiting, diarrhea, we have really lots of choices for anti-nausea medicines and different combinations we can use or newer antiemetics that can help with that. And from a diarrhea perspective it depends on the treatment. But, of course, we want to make sure first and foremost there’s no infection. And if not, then there are good antidiarrheals we could add on to the regimen to help with that as well.  

Thriving With AML | Advice for Setting Goals and Making Treatment Decisions

Thriving With AML | Advice for Setting Goals and Making Treatment Decisions from Patient Empowerment Network on Vimeo.

When facing an acute myeloid leukemia (AML) diagnosis, treatment decisions may feel overwhelming. AML specialist Dr. Alice Mims shares expert guidance for setting treatment goals with your team, advice for making care decisions, and explains how tests results may impact choices.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims.

See More from Thrive AML

Related Resources:

Phases of AML Therapy | Understanding Treatment Options

Expert Advice | Managing AML Symptoms and Treatment Side Effects

Stem Cell Transplant for AML | What Patients Should Know


Transcript:

Katherine Banwell:

One part of thriving with AML is finding a treatment approach that manages your disease and fits with your lifestyle. Before we talk about therapy, can you tell us how treatment goals are established for an individual patient? 

Dr. Alice Mims:

Sure. So, for individual patients, I think it’s very important that there is an initial discussion that doesn’t feel too shortened that you can have time with your care team to really go into depth about the diagnosis, about the specifics of your particular subtype of acute myeloid leukemia, understanding the treatment options, and then being given time allowed to reflect on all of that information. So, then you can come back and have your questions better answered that may come from that initial discussion. 

And then help you with your team make a decision based on that information that works best for you.  

Katherine Banwell:

Outside of patient preference, what other factors do you take into account when working with a patient to decide on a treatment plan? 

Dr. Alice Mims:

Sure. So, there are multiple different factors that we try to take into account. Again, yeah, most importantly what patients’ goals are like you mentioned, but those include overall health, including different comorbidities, so what other healthcare diagnoses, medications are you taking, what are the patients’ age, thinking about that for long-term goals, overall support from loved ones, family to — just because care can be really involved. And then in particular, thinking about specific features of that individual patient’s AML, including molecular, genetic features of the leukemia. 

Katherine Banwell:

Well, let’s talk more in depth about the test results you just mentioned. 

What is the test for genetic markers? And how is it conducted? 

Dr. Alice Mims:

So, there are a few different tests that we use under that scope of genetic markers. So, those include looking at chromosomal abnormalities of the DNA. So, with cytogenetics, and then also more specific prose where we call FISH testing. And then also we look for specific gene mutations through next-generation sequencing, or PCR testing. And so, we use all of those results together to give us the most information we can about that individual’s leukemia. 

Katherine Banwell:

How has molecular testing revolutionized AML care? 

Dr. Alice Mims:

Oh gracious. It’s really done such – so much for leukemia. And just things are so different even where they were five years ago because of having molecular mutations, that information available. 

So, it helps with discussing prognosis. So, we know that different molecular features can tell us about curative intent and what are the treatment steps we would need to take to give the best chance long-term. And then also now, we’ve evolved to where we have directed therapies that can target mutations or the proteins that arise from those mutations with therapeutic options. 

Katherine Banwell:

Is this testing standard following an AML diagnosis? 

Dr. Alice Mims:

It is standard following an AML diagnosis. That’s recommended within all of the guidelines with patients and really should be done for all patients at initial diagnosis. 

Katherine Banwell:

Can genetic markers or mutations change over time? For example, if a patient relapses, should molecular testing be done again? 

Dr. Alice Mims:

Yes, absolutely. Mutations can evolve. It’s something we call clonal evolution of the leukemia. 

And so you can have mutations that could be present at diagnosis that may no longer be present. Or the opposite can occur where you have new mutations that can appear. And that can lead to different options for treatment. So, it’s very important to retest at time of relapse.  

Katherine Banwell:

What advice do you have for patients who want to ensure that they’ve actually undergone molecular testing? What questions should they be asking their healthcare team? 

Dr. Alice Mims:

I think it’s definitely important to bring this up with the healthcare team. And it should be something at diagnosis and relapse to ask, what are the cytogenetics, what do they look like now, what do the gene mutations, and really as mentioned before, it’s so crucial in talking about prognosis, talking about treatment options that if it doesn’t come up, it’s really something that you should take a pause and try to go back to readdress with your team.  

PODCAST: Managing Life With AML | What You Should Know About Care and Treatment

 

What do you need to know when it comes to managing life with acute myeloid leukemia (AML)? In this webinar, Dr. Alice Mims, an AML specialist and researcher, discusses how treatment decisions are made and how test results may impact therapy. Dr. Mims will shares the latest advances in research and key advice for living well with AML.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. Dr. Mims serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James. Learn more about Dr. Mims.

Download Resource Guide

See More from Thrive AML


Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for today. Today’s program is a continuation of our Thrive series. And we’re going to discuss navigating life with AML, and how you can engage in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, joining us today is Dr. Alice Mims.  

Dr. Mims, welcome. Would you please introduce yourself? 

Dr. Alice Mims:

Yeah, sure. Thank you, Katherine. I’m Alice Mims. I’m a physician and associate professor at Ohio State University. And also, the section head for the myeloid and acute leukemia program within our division of hematology. 

Katherine Banwell:

Thank you so much for taking the time to join us today, Dr. Mims. We start all of our webinars in our thrive series with the same question; in your experience, what does it mean to thrive with AML? 

Dr. Alice Mims:

Sure, I think that’s a great question. So, really for me, I think thriving with AML is very patient- or person-dependent. It really depends on making sure that your treatment goals align with your care. And so that means really being an active participant in your diagnosis, understanding the disease process, and making sure that your care team really understands what your overall goals are for your treatment. 

Katherine Banwell:

Thank you for that because it helps us to understand as we move through the program today. One part of thriving with AML is finding a treatment approach that manages your disease and fits with your lifestyle. Before we talk about therapy, can you tell us how treatment goals are established for an individual patient? 

Dr. Alice Mims:

Sure. So, for individual patients I think it’s very important that there is an initial discussion that doesn’t feel too shortened that you can have time with your care team to really go into depth about the diagnosis, about the specifics of your particular subtype of acute myeloid leukemia, understanding the treatment options, and then being given time allowed to reflect on all of that information. So, then you can come back and have your questions better answered that may come from that initial discussion. 

And then help you with your team make a decision based on that information that works best for you. 

Katherine Banwell:

Outside of patient preference, what other factors do you take into account when working with a patient to decide on a treatment plan?  

Dr. Alice Mims:

Sure. So, there are multiple different factors that we try to take into account. Again, yeah most importantly what patients’ goals are like you mentioned, but those include overall health, including different comorbidities, so what other healthcare diagnoses, medications are you taking, what are the patient’s age, thinking about that for long-term goals, overall support from loved ones, family to — just because care can be really involved. And then in particular, thinking about specific features of that individual patient’s AML, including molecular, genetic features of the leukemia. 

Katherine Banwell:

Well, let’s talk more in depth about the test results you just mentioned. 

What is the test for genetic markers? And how is it conducted? 

Dr. Alice Mims:

So, there are a few different tests that we use under that scope of genetic markers. So, those include looking at chromosomal abnormalities of the DNA. So, with cytogenetics, and then also more specific prose where we call FISH testing. And then also we look for specific gene mutations through next generation sequencing, or PCR testing. And so, we use all of those results together to give us the most information we can about that individual’s leukemia. 

Katherine Banwell:

How has molecular testing revolutionized AML care?  

Dr. Alice Mims:

Oh gracious. It’s really done such – so much for leukemia. And just things are so different even where they were five years ago because of having molecular mutations, that information available. 

So, it helps with discussing prognosis. So, we know that different molecular features can tell us about curative intent and what are the treatment steps we would need to take to give the best chance long-term. And then also now, we’ve evolved to where we have directed therapies that can target mutations or the proteins that arise from those mutations with therapeutic options. 

Katherine Banwell:

Is this testing standard following an AML diagnosis? 

Dr. Alice Mims:

It is standard following an AML diagnosis. That’s recommended within all of the guidelines with patients and really should be done for all patients at initial diagnosis. 

Katherine Banwell:

Can genetic markers or mutations change over time? For example, if a patient relapses, should molecular testing be done again? 

Dr. Alice Mims:

Yes, absolutely. Mutations can evolve. It’s something we call clonal evolution of the leukemia. 

And so you can have mutations that could be present at diagnosis that may no longer be present. Or the opposite can occur where you have new mutations that can appear. And that can lead to different options for treatment. So, it’s very important to retest at time of relapse. 

Katherine Banwell:

What advice do you have for patients who want to ensure that they’ve actually undergone molecular testing? What questions should they be asking their healthcare team? 

Dr. Alice Mims:

I think it’s definitely important to bring this up with the healthcare team. And it should be something at diagnosis and relapse to ask, what are the cytogenetics, what do they look like now, what do the gene mutations, and really as mentioned before, it’s so crucial in talking about prognosis, talking about treatment options that if it doesn’t come up, it’s really something that you should take a pause and try to go back to readdress with your team. 

Katherine Banwell:

I’d like to move on to treatment now, Dr. Mims. And, of course, treatment takes place in phases for AML. The first is induction therapy. Can you start by defining induction therapy for our audience? 

Dr. Alice Mims:

Sure. So, induction therapy is really terminology that we use to talk about initial therapy for someone with a new diagnosis. So, we can have intensive induction therapies, and non-intensive induction therapies. But the goal for either of those types of treatment is to get the leukemia into remission. 

So, to talk about that in a little bit more detail, for intensive induction regimens, those typically involve cytotoxic chemotherapy. So, you may hear terminology like, “7 + 3 induction,” or “high-dose cytarabine regimens,” but those are typically more intensive regimens that we use that can have increased side effects but may be very important based off the type of acute leukemia. 

And then for non-intensive based regimens, one of the standards has really evolved to be venetoclax (Venclexta) and azacitidine (Vidaza) as a non-intensive regimen that can work very well for a majority of patients. And there are some off shoots of that as well. 

Katherine Banwell:

Okay. And when does stem cell transplant come into play? 

Dr. Alice Mims:

Sure. So, stem cell transplant is something that we all think about at the beginning for anyone with a new diagnosis of acute myeloid leukemia where as we’re working to get back genomic information about the individual’s acute leukemia, we may go ahead and start looking for different donors, doing typing, just in case that’s something that we need as far as someone’s therapy. 

But typically we reserve stem cell transplant for patients who have either intermediate or high-risk features of their AML. Or who may have even favorable respite are not responding as well as we would like when looking at the depth of remission. And so, we always want  to be prepared in case that’s something we need to move forward with as part of their care, if the goal of their treatment is for curative intent. 

Katherine Banwell:

Let’s talk about what happens after the initial phase of treatment. What’s the purpose of consolidation therapy? 

Dr. Alice Mims:

Sure. So, there are a few different purposes we can use consolidation therapy for. So, for patients – consolidation therapy is used for patients who have achieved remission. And then it’s either to try to hopefully get them cure of their AML. The patients have more favorable risk features of their AML and cure is an option through just chemotherapy alone. 

Or it can be used to try to keep people in remission while we’re working to get towards stem cell transplant as that can sometimes take a few months to get a donor ready, have things ready to move forward with transplant. 

Katherine Banwell:

And what are the options for consolidation therapy?  

Dr. Alice Mims:

Sure. So, options for consolidated chemotherapy are typically based off of what you had initially for induction chemotherapy. So, if it’s more intensive-based regimens, it typically is consolidation with intensive consolidation, cytarabine based regimens.  

For lower intensity regimens, typically consolidation is more continuing therapy on what you started but may have adjustments of the treatment based off of trying to decrease the toxicity now that the patients are in remission. 

Katherine Banwell:

And how are patients monitored in consolidation therapy? 

Dr. Alice Mims:

Sure. So, it definitely is based off of the individual’s type of consolidation chemotherapy or treatment. But most patients, if we feel like the treatment is going to lower blood counts, they have bloodwork twice a week, and we’re watching for things, for side effects for treatment, looking out for risk of infection, giving transfusion support, and then if something happens that we feel like we can’t support patients in an outpatient setting, then we’ll get them back into the hospital if they need to for care. 

Katherine Banwell:

What side effects are you looking for?  

Dr. Alice Mims:

So, most of the side effects with any of the treatments that we give are what we call myelosuppressives. So, it lowers the different types of blood counts.   

So, white blood cell count which increases risk of infection, red blood cells, so, side effects or symptoms from anemia. And then risk of bleeding from low platelet counts.  

Katherine Banwell:

Okay. Maintenance therapy has become more common in other blood cancers particularly in multiple myeloma. Is there a role for maintenance therapy in AML? 

Dr. Alice Mims:

There actually is now, which is something that’s newer that has evolved for acute myeloma leukemia. So, in the context of intensive therapy, we now have oral azacitidine (Onureg), which is a little bit different than some of the IV formulations that we give.  

But for patients who receive intensive induction therapy, get into remission and may receive consolidation but are not able to go onto transplant if they have that immediate or higher risk features, there’s FDA approval for oral azacytidine, which has been shown to improve overall survival and keep people in those remissions for longer. 

More recently, specifically for patients who have a particular type of mutation called FLT3, if they also receive intensive induction therapy with a FLT3 inhibitor added onto that, then their quizartinib was just recently approved as a maintenance therapy for patients with that particular type of AML.  

Katherine Banwell:

Are there emerging AML therapies that patients should know about other than what you just mentioned? 

Dr. Alice Mims:

Sure. So, I think there are a lot of exciting treatments that are up and coming based off of many small molecule inhibitors that are being studied. 

One in particular I would mention that everyone’s very excited about is a class of agents called menin inhibitors.  

And so that’s an oral agent that has been shown to have responses for patients with relapse or refractory AML who have NMP-1 mutations or have something called KNT2A rearrangements. And seeing responses with just a single agent in the relapse refractory setting, it’s been really exciting. And so, I think we’re hopeful that that may become FDA-approved in the near future. And it’s also now being explored in combination with intensive chemotherapies as well as less intensive induction regimens. And so, maybe we can do a better job without brunt treatment by adding these therapies on. 

Katherine Banwell:

That’s exciting news. When it comes to living and thriving with AML, Dr. Mims, managing disease symptoms and treatment side effects is a big part of that. 

Would you talk about how symptoms and side effects can impact life with AML?  

Dr. Alice Mims:

Sure. So, I think from my perspective, what we are always trying to do when we’re moving forward with a treatment plan is of course, get patients into remission, but the purpose of getting into remission is not just to achieve that, but for patients to have quality of life. And so, there needs to be continued dialogue between the patient and the treatment team about how you’re feeling during treatment. Because they’re definitely based off of therapy, different side effects, things that could be not necessarily due to active leukemia anymore. And so there may need to be dose adjustments and other things that we do to the regimens in order to make you feel as good as possible while continuing on treatment. 

Katherine Banwell:

Why is it so important for patients to speak up about any issues they may be having? 

Dr. Alice Mims:

I think it’s important because you’re your own best advocate. Being the patient, being the person who’s living with having this diagnosis and going through the treatment, myself, or other colleagues as physicians, we can have a sense of what may be going on based off of numbers. But we’re not truly going to know how you’re feeling unless you speak up and let us know. And there may be things we could do with supportive medications, dosing adjustments as mentioned, that could help in making you hopefully feel better and less side effects and toxicities from treatment. 

Katherine Banwell:

What are some common symptoms and side effects that you hear about?  

Dr. Alice Mims:

Okay. Sure. So, different side effects that I would say that people can have, people can feel fatigued just from treatment in general. Some of our therapies can cause neuropathy, skin rashes, nausea, vomiting, diarrhea. And so, all of those are important along as mentioned with symptoms you may have from decreased blood counts that we do have interventions that we could implement to help the – make the therapy more tolerable. 

Katherine Banwell:

So, for the side effects like fatigue for example, what do you do about that? 

Dr. Alice Mims:

So, I think it depends on the level of fatigue. Of course, we don’t have – I wish we had a pill that could just make fatigue improve. But if it’s really that the treatment is deriving it, and it’s impeding your quality of life there are dose reductions or things we can do that may help with the level of fatigue you’re experiencing.  

Katherine Banwell:

And what about some of the other side effects. You mentioned diarrhea. 

Dr. Alice Mims:

Sure.  

Katherine Banwell:

How is that handled? 

Dr. Alice Mims:

Yeah. So, for issues from GI complications such as nausea, vomiting, diarrhea, we have really lots of choices for anti-nausea medicines and different combinations we can use or newer antiemetics that can help with that. And from a diarrhea perspective it depends on the treatment. But of course, we want to make sure first and foremost there’s no infection. And if not, then there are good antidiarrheals we could add on to the regiment to help with that as well. 

Katherine Banwell:

Okay. That’s great advice. Thank you. I want to make sure that we get to some of the audience questions. These were sent to us in advance of the program today. Let’s start with this one; Janet wants to know what factors enable a patient to achieve and continue in remission if they are not able to achieve stem cell transplant due to age restrictions.  

Dr. Alice Mims:

So, I think first and foremost, I think it’s very important that there — that patients are aware that there shouldn’t be just strict, stringent cutoffs of age as a requirement for stem cell transplant. And really, there’s a lot of research going on that we should take into account. Physiological age, and there’s ways to measure that just to be sure that stem cell transplant really is not an option. And for patients who stem cell transplant is not an option, I think as we talked about earlier, so there can still be really great treatments that can get patients into remission and ongoing therapies with dosing adjustments again to decrease toxicity and improve quality of life and thinking about things like maintenance therapy as appropriate. 

Katherine Banwell:

What are the age restrictions, and why are they there? 

Dr. Alice Mims:

So, sometimes you will hear age 75.

Really, no one above age 75 should move forward with transplant. And that’s based off of past data where they’ve explored transplant and seen increased toxicity. And from transplant in itself, increased side effects, increased risk of early mortality. And so, I do think it’s important to take the patient as a whole into consideration because again, you could have someone who’s 77 who may be running marathons, and in great shape, and not a lot of other healthcare issues, who may still do really well with treatment. And so, I think that’s – really needs to be taken in account, really the overall picture of health for the patient before making… 

Katherine Banwell:

So, the… 

Dr. Alice Mims:

…just a firm cutoff. 

Katherine Banwell:

Right. Okay. So, it’s not cut and dry. 

Dr. Alice Mims:

Exactly. 

Katherine Banwell:

If you’re 75 or older, then you definitely can’t have stem cell transplant. 

Dr. Alice Mims:

That’s correct. 

Katherine Banwell:

Then you’re looking at everyone individually. 

Dr. Alice Mims:

Yeah. So, it really should be looked at.  

And I still have some patients who will come to me and say, “Oh, I was told I’m 68 years old, I’m not a candidate.” And that always makes me take a step back. And then we kind of have to have that discussion again. And they may still not be a good candidate based off of other comorbidities or healthcare issues, but it shouldn’t just be a number rules you out for having that as an option. 

Katherine Banwell:

Good to know. We received this question from Carl, “What does treatment look like following transplant? And what are doctors looking for when monitoring through blood tests?” 

Dr. Alice Mims:

Sure. So, after transplant, the first three months is pretty intensive of being seen very frequently at your transplant center twice to once a week. You’re also on immunosuppressive medications to try to help prevent issues like graft vs host disease, which can be a complication from transplant. 

And then over time if you’re doing well, we try to start tapering off those immunosuppressive regimens to see if you can tolerate that. And what I say to most of my patients for – who are undergoing transplant, it can take some time to really feel back to being yourself. It can take six months, it can take a year or longer. And sometimes your normal is a new normal based off of how you do and the side effects of the transplant in itself. So, you may not go back to if you’re here before transplant and before your diagnosis, it may be that this is your new normal. Just so people can be prepared and know what they’re signing up for.  

Katherine Banwell:

And with the blood testing, what are you looking for when you’re monitoring a patient?  

Dr. Alice Mims:

Sure. There are a few different things that we’re looking for when monitoring patients. So, one, making sure that the stem cells or the graft from the donor are recovering. 

You want to see that blood counts, levels of white blood cells, red blood cells, platelets are getting to normal levels. You’re also assessing and making sure you’re not seeing signs of relapse. You’re checking levels of donor cells versus the patient cells within the stem cell — sorry, within the stem cell compartments. And so, we’re taking all of those into account as well as checking organ function and making sure there’s no signs of potential graft versus host disease as well. 

Katherine Banwell:

Katrina sent in this question; do you have any advice for dealing with a general oncologist who does not exactly follow my AML doctor’s recommendations? I see a local oncologist and an AML specialist guides my care. 

Dr. Alice Mims:

I think that’s a tough question. And so, I think I’ll answer that if – maybe two different ways. 

So, one, I think sometimes it’s hard when you’re the local community oncologist, and you’re there for the day-to-day care. And so there may need to be treatment adjustments and other things that you need to do in that moment or time to help make sure that toxicities are not too severe or are helping the patient as you’re seeing them day-to-day. And it may not be easy to involve the specialist right there in the moment. But I think if there are bigger issues as far as overall goals, overall communication, it should be that both are able to communicate well with each other. They should be able to communicate via email, via text message. That’s what I do with a lot of my community partners. And it’s always important that you as a patient feel confident in your care. And so, if that trust is not there that things are being followed, then it may be important to look and see if there’s another physician who you do feel comfortable with proceeding with your care with. 

Katherine Banwell:

And what do you tell patients when they’re not feeling comfortable with their care team or their oncologist or their general oncologist? What do you say to them to give them some confidence to find somebody else who they feel more comfortable with? 

Dr. Alice Mims:

Sure. So, I’ll just say from my perspective. So, if I’m seeing a patient and they may have questions, they may not feel comfortable, they may need more time. And I always think it’s important if you want a second opinion, whether it’s at a specialist level, whether it’s in a community oncology private setting, that should not be offensive to the physician.  

If that makes the patient feel more comfortable in what they’re doing with their care, that’s how they should move forward. And it should be what they feel like is best. If a physician takes that personally or is offended by it, I think that’s more of their problem as opposed to anything that you’re doing wrong.  

Katherine Banwell:

Okay. Thank you for that. Ryan wants to know; I’m a year and a half post-transplant, how can you tell if the aches and pains in your joints are normal aging, host vs graft disease, the AML returning, or even something else? 

Dr. Alice Mims:

So, I think that’s also a difficult question to answer because it really is patient dependent. And so, I think if you’re having new joint aches or pains, it’s always important to reach out to your transplant team to make sure that – it could be any of the above.. 

And so you’re doing the appropriate workup with lab work, imaging, things that would be appropriate or seeing certain specialists. Maybe orthopedist if needed because it could be I’d say less likely leukemic relapse, but still want to be sure. But it could be definitely complications from GVHD or there’s some joint issues that can evolve post-transplant, especially for people who are on long-term immunosuppressant medications. Or it could be the normal effects of aging. So, it’s always good to have that reassurance. 

Katherine Banwell:

Let’s talk a little bit about mental health resources. Managing the worry associated with a diagnosis or concerns about relapse, or even various side effects can lead to emotional symptoms like anxiety and fear.  

Why is it important for people with AML to share how they’re feeling with their healthcare team? 

Dr. Alice Mims:

So, I think it’s very important because, one, all of those feelings are normal feelings. I think they’re sometimes that from going through such a rapid diagnosis and then having to start treatment pretty quickly and going through all the ups and downs with these types of diagnosis can really lead to for some patients PTSD-type symptoms. And then there are also things that can evolve over time where their anxiety or even survivorship guilt as you go if you move forward and are doing well where you may have some friends or people you met along the way who may not have had as good outcomes. And so, there are resources available based off of where you are.  

But for survivorship, oncology specific counseling to deal with some of these feelings that are understandable and normal for what patients have been through. 

Katherine Banwell:

Can a social worker help? And are there other people on the healthcare team who can support a patient’s emotional needs? 

Dr. Alice Mims:

Oh, absolutely. So, I think it’s really place-dependent on where you are but yes, absolutely. Social workers are a great resource for patients. There may be other collaborative teams based off of where you’re receiving your treatment that may be available that are maybe patient support groups where you can go and be with other patients or Facebook, social media support groups. And I think all those can be very helpful. And I know at least at our center, we also have patient mentors who have been through and gotten through to the other side of transplant or whatnot who are great resources because they’ve lived and experienced it. 

And I think that’s just as a physician, I can talk about things that I don’t have that personal experience having lived through it. And I think that’s very important — 

Katherine Banwell:

Yeah. It’s a… 

Dr. Alice Mims:

…to be able to have somebody to talk to. Yeah. 

Katherine Banwell:

Yeah. What about the financial aspect of treatments? There are many people who would find it difficult to find and maybe they don’t have insurance, or their insurance doesn’t cover a lot. How do you help patients who are dealing with financial restrictions?  

Dr. Alice Mims:

Sure. So, I think that we’re fortunate here because we have a lot of support staff to help patients with our financial counseling team. We also have people within the medication assistance programs who can help find foundation grants to help with medication support, travel support. 

I think for patients who may not have those things available at their individual center, The Leukemia & Lymphoma Society is a great place to reach out for.  

And there are other foundations as well who at least may have navigators to help patients figure out other resources or funding available. 

Katherine Banwell:

Yeah. Okay. That’s really good information, Dr. Mims. Thank you. And please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. Well, Dr. Mims as we close out our program, I wanted to get your thoughts on where we stand with progress in AML care. Are there advances in research treatment that you’re hopeful about? 

Dr. Alice Mims:

Yes. I would say from even when I finished fellowship 10 years ago, not to state my age, but we had essentially about three treatments at that time. 

Now in the past five years there have been I think maybe 11 different new drugs that have been approved for a acute myeloma leukemia. And so, I think we’re just on the precipice of really evolving to have individualized care. Hopefully have more curative options for patients. So, I’m really excited for the time we’re in right now where I even hope we’ll be in the next five years for patients. 

Katherine Banwell:

That’s an encouraging message to leave the audience with, Dr. Mims. Thank you so much for joining us today. 

Dr. Alice Mims:

Thank you so much for letting me be here with you today. 

Katherine Banwell:

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