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Factors to Consider When Choosing an AML Treatment

Factors to Consider When Choosing an AML Treatment from Patient Empowerment Network on Vimeo.

What test results and factors should be considered when choosing an acute myeloid leukemia (AML) treatment? Expert Dr. Ellen Ritchie explains how test results impact AML prognosis and treatment – and other factors that come into play when determining a treatment approach.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

How do the results of these tests affect prognosis and treatment?

Dr. Ritchie:

Well, when a patient has AML, if they are a fit patient, if it will help us determine after initial induction, whether to cure the patient we need to do a bone marrow transplant, or we can just continue with chemotherapy.

And those are really important things to determine. So, if you have a good prognosis AML, if you have an AML that has certain translocations like inversion 16 or 821, or if you have a CEPBA mutation or you have an NPM1 mutation, and that’s all you have, you may do particularly well with chemotherapy treatment alone. And you won’t need to have a bone marrow transplant.

If you have certain other mutations, we know that the only way that we’re going to cure you, is with a bone marrow transplant. And if you are fit, when we finish induction and even as we’re doing induction, we’re preparing you for a bone marrow transplant down the line.

One disadvantage, just to mention about the molecular testing, is it doesn’t come back as quickly as some of the other testing. So that you will have already started induction chemotherapy most generally before the mutational testing comes back. Which can be anywhere – depending upon the institution, between seven and 21 days. So, it takes time for those results to be available.

Katherine:

Outside of test results, Dr. Ritchie, what other factors should be considered when choosing treatment?

Dr. Ritchie:

So, you want to choose whether a patient is most likely to benefit from intense induction chemotherapy. With strong chemotherapies where the backbone of those therapies would be an anthracycline, like daunorubicin (Cerubidine) or cytarabine (Liposomal), or daunorubicin or idarubicin (Idamycin PFS), together with cytarabine. And these are intensive chemotherapies. Versus, non-intensive chemotherapy which is able to be done as an outpatient, more frequently. And it is something that is gentler for a patient, they’re less likely to have severe toxicity. And the backbone of those regimens is using a drug called azacitidine (Vidaza) or decitabine (Inqovi), together with a second drug called venetoclax (Venclexta).

So, these are the two backbones, there may be clinical trials or there may be targetable aspects of your leukemia, which drugs would be added to either of those backbones. But those are the two backbones. And I also like to identify those patients that may not benefit from chemotherapy at all. And so, it’s very important, I think to really get to know your patient. And I spend time with my patient, particularly on the first visit, to understand not only their physical health, but their mental health. How good is their cognition, what is their mood, are they depressed, or are they happy people? And what is their circumstance? Do they have people to support them? Do they live close to family? Is a caregiver able to come, with an elderly patient for example, to visits?

Those, and whether or not they’re living alone and need tremendous support. So that’s really important to determine and helps me to choose what the best therapy might be. And also, concurrently what I can do to shore up the patient to do better with whatever therapy that I’m giving them. I.e., if you’re depressed, let’s work on that, or if your blood pressure is too high, or if you are – your diabetes is out of control at the same time that I’m seeing you, to try and fix those particular problems. In older patients I often do sort of a miniature version of the geriatric assessment. And in trials that have been so far, the most important aspects of the geriatric assessment, are really what is your cognitive function? Do have a mild dementia, or do you not have a mild dementia? Because dementia may be or mild dementia may be associated with poorer outcome.

The other is, are you able to do what we call the incidental tasks of daily life. So, you know fundamental tasks are really brushing your teeth and combing your hair, and dressing yourself. But are you able to do your cooking and your shopping and your banking and those things? Patients who have trouble doing their cooking and shopping and banking, and those types of activities, that also has been associated with a poor overall survival in AML. So, it’s really important to determine all of those aspects and if there are any deficiencies, to really know that the only therapeutic choice for that particular patient would be a low-intensity therapy.

Understanding Key Tests That Affect AML Treatment Choices

Understanding Key Tests That Affect AML Treatment Choices from Patient Empowerment Network on Vimeo.

For acute myeloid leukemia (AML), test results play a vital role in determining the most appropriate treatment option. Expert Dr. Ellen Ritchie reviews key tests used to pinpoint a patient’s specific AML, how the test results are utilized, and important questions patients should ask their doctor about AML testing. 

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Related Resources:

Essential Testing in AML: How Results Impact Care & Treatment Choices


Transcript:

Katherine:

So, let’s help our audience be clear about basic testing. What tests are necessary to help understand a patient’s specific disease at diagnosis?

Dr. Ritchie:

I mean certainly it’s important to do a physical exam and to find out what the general health of the patient is. In order to evaluate an AML, or any other leukemia, I look at the peripheral blood smear. To look at what I think the type of leukemia might be that I am dealing with. There are some leukemias that have particular way that they look like acute promyelocytic leukemia for which there is a designated therapy which works.

And you can tell that just by looking at a peripheral blood slide. The next test is always a bone marrow biopsy. Patients are not delighted that that is a test, but it is a test that can be done in the office, usually within 15 to 20 minutes. And that test gives us a lot of information. It gives us information about what type of AML it is, what are the markers on the outside of the cell, it gives us information about the chromosomes inside the leukemia cell. Are there missing chromosomes, or rearranged chromosomes? And if there are, that can be very relevant to the prognosis. And lastly, it’s sent for a particular mutations or markers. So, we look for IDH3 mutations, we look for FLT3 mutations, we look for IDH1 and IDH2 mutations, and we do an entire myeloid panel. Which is about 44/45 genes that are most commonly mutated in patients with AML. So that’s the initial work-up for any AML patient.

Katherine:

You mentioned markers, Dr. Ritchie. What is genomic, or biomarker testing?

Dr. Ritchie:

So, we’re looking really at most specifically at mutations inside individual genes that might be in your leukemia cell. So, there are some mutations actually that confer a better prognosis. Like NPM1 or CEPBA, those can be more positive type of prognosis than some of the others.

But we’re also looking for markers that might be targetable with certain therapies that we have. So, if you have a FLT3 ITD or TKD, we actually have particular drugs which can target those particular mutations. There are also drugs that are FDA approved to treat IDH1 and IDH2 mutations.

There are certain mutations that have a relatively poor prognosis, like TP53 for which there are clinical trials which are available, which specifically are meant to target patients who have those sorts of mutations. And there’re other clinical trials using the FDA-approved drugs that I just mentioned, for FLT3, for IDH1 and IDH2 and combining it with other agents to try and improve outcome in AML patients.

Katherine:

Some patients may not know if they’ve received these important tests, so what key questions should they be asking their physician about testing?

Dr. Ritchie:

So, physicians, they – financial coverage of the mutational testing is not uniform across the country and across insurances. So, Medicare and different Medicare insurances and some of the private insurances all vary in their coverage.

So, in my clinic, I am asking – I prefer the test that we do in house at Cornell. But it’s important that I ask, what will their insurance cover. And make sure that I send the appropriate testing that will be covered by insurance. There are some insurances that will not cover this type of testing. So, it is a real question for the patient, when you go to see the doctor to say, are you going to do mutational NGS testing?

And, will my insurance cover this? Hopefully most – if Medicare adopts the coverage of these types of mutational testing, it’s often true that private insurance will eventually pick this up. But it’s a murky field, and it’s really important to talk to your doctor about this. The cost of the bone marrow biopsy, and the chromosomal evaluation is nearly always covered by insurance.

Understanding Personalized Medicine for AML

Understanding Personalized Medicine for AML from Patient Empowerment Network on Vimeo.

What should you know before deciding on treatment for YOUR AML? AML specialist Dr. Ellen Ritchie reviews key factors that guide treatment choices, including biomarker testing results, and shares advice for partnering with your team to advocate for the best care.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

As we begin to talk about personalized therapy and AML, let’s start with the basics. How would you define personalized medicine?

Dr. Ritchie:

Personalized medicine, to me is really, it’s a difficult question. It’s trying to find the best treatment for a particular patient. And it’s looking at biologic issues, what kind of cancer, what type of AML is it, what are the specific mutations or chromosomal abnormalities. But it’s also looking at the person. Is the patient active or not active? Do they have lots of other diseases like diabetes and coronary artery disease? Or pulmonary disease, or are they completely healthy?

Or, do they have support at home? If they’re sick at home is there someone who can take care of them, versus a situation where you’re older and alone and you have no real family member to rely on. So, all of these things are very important in making a personalized decision as to how you treat a patient.

Which Metastatic Breast Cancer Treatment Is Right for You? What You Need to Know

Which Metastatic Breast Cancer Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What do you need to know before deciding which treatment is best for YOUR metastatic breast cancer? Expert Dr. Jane Meisel reviews recent research news, discusses the role of key tests–including biomarker testing –in determining a treatment plan, and shares advice for self-advocacy.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel, here.

[Editor’s Note: On August 23, 2021, the U.S. Food and Drug Administration (FDA) approved the Pfizer-BioNTech COVID-19 Vaccine for individuals 16 years of age and older.]

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What Could Advances in Breast Cancer Research Mean for You?

How Can You Advocate for the Best Breast Cancer Care?

Factors That Guide a Metastatic Breast Cancer Treatment Decision

 


Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. In today’s webinar, we’ll discuss how you can access the most personalized metastatic breast cancer therapy for your individual disease and why it’s vital to insist on key testing. Before we meet our guest, let’s review a few more important details. The reminder email you received about this program contains a link to program materials.

If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today, in order to help plan future webinars. And finally, before we get into the discussion, please remember, this program is not a substitute for seeking medical advice. Please refer to your healthcare team – Please refer to your healthcare team about what might be best for you.

All right, let’s meet our guest today. Joining us is Dr. Jane Meisel. Dr. Meisel, welcome. Would you please introduce yourself?

Dr. Meisel:

Absolutely and thank you so much for having me. My name is Jane Meisel and I’m a medical oncologist at the Winship Cancer Institute at Emory University. I’ve been here for about six years and before that, I did my training in Boston and at Memorial Sloan-Kettering in New York. And I specialize in breast cancer and have had a lot of great opportunities to treat amazing patients and participate in a lot of research.

And I’m looking forward to having this discussion with you today.

Katherine:

Thank you for joining us, we really appreciate it. So, let’s start by discussing the latest developments in treatment and research updates. Are there recent developments you feel breast cancer patients should know about?

Dr. Meisel:

Absolutely and I think it’s really been such a remarkable time because even during COVID, a pandemic, where I think a lot of people worried that research efforts would shut down or stall. We’ve still seen the approval of a number of drugs in the past year that’ve really already markedly changed lives. And a lot of important findings that’ve come out of other trials that they have opportunity to do that as well.

I think some of the biggest information that was presented at our most recent large meeting, which was the American Society of Clinical Oncology, or ASCO National Meeting in 2021, were a few things that pertain to the metastatic breast cancer population. One was two studies, the PALOMA-3 Trial and the MONALEESA-3 Trial, which looked at a class of drugs called CDK4-6 inhibitors along with anti-estrogen pills in metastatic estrogen-positive breast cancer.

And really confirm for patients that not only do these drugs improve the amount of time that people can stay on treatment before their cancer progresses, but actually improve how long people live. Even when they’re used very, very early on in treatment, they impact survival down the line for many, many years. So, it really confirms for physicians like me that this class of drugs should be used as the standard of care and first line for patients with estrogen-positive stage IV breast cancer, and I think that’s important for patients to know. Along those lines, there a drug called sacituzumab govitecan, or Trodelvy, which is a much easier to say name.

Katherine:

Yes.

Dr. Meisel:

A new antibody drug conjugate in triple-negative metastatic breast cancer. And we’ve also seen, since this drug was approved last year, it has markedly changed the lives of many patients with triple-negative disease. And the study called the ascent trial, which is what led to that drug’s approval was studied further and some of these additional results presented at ASCO this year.

And found that this drug not only improves again, how long people get before they have to move on to another treatment, but actually improves how long people live as well, even when given later on in the course of therapy. So again, really encouraging use especially in triple-negative metastatic disease, which is hard to treat. And I think another study that’s really worth patients and doctors taking a hard look at, was actually a study that looked at patient outcomes and patient experience. This is a study that actually talked with metastatic patients and gathered their views on treatment related adverse effects.

Talked to patients about what adverse effects they were experiencing from drugs. How they managed those adverse effects. And found that most patients, over 90%, will be willing to talk about reducing the dose of drugs or changing dosing schedules, in order to improve quality of life. And I think that’s really important because a lot of times, the doses of drugs that get approved are the doses that are the highest doses that don’t cause extreme toxicity. But sometimes people can have effective, really good outcomes on lower doses and have much better quality of life.

And in metastatic breast cancer where really the goal often times is to help people live as long as they can, but also as importantly, as well as they can, be able to have those open-ended conversations between patients and doctors about what’s really impacting your quality of life now and how can we make that better is important. And this study I think really highlighted that both for patients and physicians, how important that back and forth is to having a successful outcome. Both in terms of how life is lived, but in terms of quality of that life.

Katherine:

Right. Right. How can patients stay up to date on developing research?

Dr. Meisel:

It’s so interesting because there is so much coming out and I think it can be hard to figure out what Phase I study that looks exciting is really going to become something, versus what really could be important in my treatment today. And what I always tell people is actually, the NCI website. So, the National Cancer Institute, has a phenomenal page looking at advances in breast cancer research. So, if you Google “NCI advances in breast cancer research,” there’s a great page that comes up. And it’s impressively up to date and I think very patient-friendly.

Breaks things down into early stage and metastatic and then in the metastatic section, talks about estrogen-positive, HER2-positive, triple-negative, which we can talk about more today but are the three big subtype of metastatic disease that dictate how we treat them. And then have links to all the different research updates and talk about what these drugs are, what the classes are and what the settings are in which they’re studied.

And so, I think that’s a really great first stop and then the links can take you to all different stuff that’s on the page that you might want to look into more in depth. And then also, the Breast Cancer Research Foundation, which is a phenomenal organization. They have a great website, too and if you click around on the website, you can see not only who they’ve donated money to that’s doing promising research, they also have podcasts, they have a blog with science and research news. I think that’s a really great site for patients to use to stay updated.

Katherine:

Let’s shift gears for a moment and talk about another time sensitive topic, COVID. Now that vaccines are available, are they safe and effective for breast cancer patients?

Dr. Meisel:

Yeah, I think the short answer to that is yes, absolutely. I’m encouraging all my patients, no matter what their treatment status is to go ahead and get vaccinated. And we are seeing now this third surge in COVID with cases rising all over the country, and really among unvaccinated populations. And with the delta variant being more transmissible, I think it’s all the more time, even if you haven’t considered vaccination up until now, to really go ahead and strongly consider getting a vaccine.

I think some of the hesitations that some of the people have talked to me about is that there were not a lot of active cancer patients, if any, included in the initial trials. And whereas that is true, it’s still the case that now, so many cancer patients have been vaccinated. We haven’t really heard about adverse effects in vaccination being something that’s higher in patients who have cancer who are on active treatment. I think the one challenge is, if you have a compromised immune system because of cancer treatment, there’s the possibility that you might not mount the same immune response to the vaccine as someone who doesn’t have cancer or isn’t getting active treatment.

So, while I would say yes, definitely get vaccinated, I would also at the same time encourage caution in saying, because you might not mount the same, 95 percent or whatever immune response, it may still be a good idea to wear a mask when you go to the grocery store, taking those precautions because no one really knows what’s coming and it’s better to be safe than sorry. But I think we will get a lot of information as the months go on about, do we need boosters? Who might need boosters more soon than others and some of that will get clarified for us, but my short answer would be yes, vaccines for all.

Katherine:

Excellent, that’s very helpful.

Dr. Meisel:

Thank you.

Katherine:

Since this webinar is focused on metastatic disease, would you define metastatic breast cancer for us?

Dr. Meisel:

Absolutely. And I think metastatic breast cancer is one of those terms that as doctors, we throw around a lot and often times don’t stop to check understanding as to what that means.

And what metastatic breast cancer is and means, is breast cancer that is spread outside of the breast and surrounding lymph nodes to another organ system. So, metastatic breast cancer, some of the most common places where it spreads are to the bone, to the skin, to the lungs, to the liver, to the brain. There are other places it can spread to. I’ve seen it on the ovaries, in the GI tract. But basically, when breast cancer spreads outside of the breast and surrounding lymph nodes to another organ system, that’s when we consider it metastatic.

Katherine:

How can a patient ensure they are getting an accurate diagnosis?

Dr. Meisel:

Another good question. And I think the most important thing when you’re considering whether or not you have a diagnosis of metastatic breast cancer is to get a biopsy of that metastatic site. So, you wouldn’t want to assume, just based on a CT scan that shows something in the bone that you have metastatic disease. Ideally, we would biopsy that spot or some spot that was indicative of metastatic disease to actually prove that there is metastatic cancer in that distant site.

Because sometimes it’s nothing. Sometimes you get scans and a little bone abnormality, maybe a scar from a prior fall. And then also, sometimes if it is metastatic, sometimes the breast cancer, the hormone receptor status, for example, can change from the primary site to the metastatic site. And that might impact treatment. So, it’s important to both get a metastatic biopsy to confirm diagnosis. And also, to understand what the treatment plan might be. And I think also for patients, just to make sure that you understand what your stage is, ask your doctor.

Say, what is my stage? Because sometimes doctors think people understand and they don’t actually, so checking that understanding is important. But if your doctor or provider is not actively checking your understanding, you can check it with them to make sure that if you are metastatic or have Stage IV disease, which is another way we define metastatic or talk about metastatic cancer, that you make sure you have the definition right.

Katherine:

Right, right. So, once someone has been diagnosed with metastatic disease, are there key tests that’re used to help understand how their disease may behave and progress?

Dr. Meisel:

Absolutely. So, I think the first thing as I said is that metastatic biopsy. Another thing that’s very important is understanding the hormone receptor status and the HER2 status of the breast cancer. And probably for a lot of you listening, if you have listened to metastatic breast cancer webinars before or maybe know someone or have had a diagnosis yourself, you’re well versed in this. But for some who may not be, I think a quick overview is maybe helpful. Breast cancer can be divided into three different subtypes. So, triple-negative, estrogen-positive or HER2-positive. And estrogen-positive breast cancer is the most common kind.

That tends to be driven by hormones and often treated with what we call, endocrine therapy. So, anti-estrogen pills, things like Tamoxifen or aromatase inhibitors are examples of that. And that’s one kind. And then there’s HER2-positive breast cancer, which is a type of breast cancer that over expresses a marker called HER2. And we now, since we know about that marker, have been able to develop a lot of different treatments that target HER2 selectively.

And can be used to treat that subtype. And then triple-negative is basically estrogen-negative, progesterone-negative and HER2-negative. And that type of breast cancer traditionally was treated essentially only with chemotherapy. But now we’ve had some breakthroughs, which we’ll talk about I think later in this program talking about immunotherapy and more targeted therapy for that. But those subtypes help determine how we treat patients. And it also can sometimes predict behavior.

I would say one of the other things that helps us predict behavior of metastatic disease is, if a patient had early-stage disease before, how quickly they developed metastatic disease. So, for example, someone who develops estrogen-positive metastatic breast cancer 12 years out from their original diagnosis is statistically more likely to have a slower progressing course of disease than someone who develops triple-negative metastatic disease very soon after their initial treatment. So, I would say that’s the primary thing we look at in terms of determining treatment plan and then predicting overall course.

Katherine:

Right. Well, let’s talk about treatment options for advanced disease.

Can you review the types of treatments available for metastatic breast cancer?

Dr. Meisel:

Absolutely. And what I’ll do is, I’ll give you a broad overview and then because there’s so much and this is such a rich environment, I mean, I give hour long lectures just about the treatment of metastatic triple-negative breast cancer to our fellows. So, there is so much meaty information here. But I’ll give an overview with some key buzzwords so then people can go look up things that matter more to them or interest them more. So, as I said, we start with thinking about, is this hormone receptor-positive or estrogen-positive breast cancer? Is this HER2-positive or is this triple-negative? And those factors really send us down different paths.

So, if someone is estrogen-positive, I had mentioned before the PALOMA and MONALEESA studies showing that CDK4-6 inhibitors, which is a class of drugs that the first one was approved in 2015 and then two others have been approved subsequently. So, relatively new drugs. But those drugs, which are pills, added to traditional anti-estrogen therapy which would be aromatase inhibitors or fulvestrant.

Are often great first-line options for these patients. And people can do well for years on just that alone, with estrogen-positive metastatic breast cancer. On average, about two years before people progress and need something new. And then after that, there are lots of trials ongoing looking at different ways in which an estrogen-positive breast cancer might progress on that regiment and how do we target that. So that there are multiple other anti-estrogen options down the line that people can use in estrogen-positive breast cancer before they need to even think about going on to something like chemotherapy.

So, really lots and lots of options for those patients, but probably starting with a CDK4-6 inhibitor plus anti-estrogen combination. And then in HER2-positive breast cancer, typically the first-line treatment would be what we call monoclonal antibodies directed at HER2. So, something like Herceptin and Perjeta, which you may have heard of. And often combined with chemotherapy. But again, this is one of those areas that is also very, I think the art of medicine is very important and patient dependent.

Some of these regiments depend a little bit on patient’s age and other medical problems and desires, whether to include chemotherapy along with that frontline anti-HER2 regimen. Or whether to think about something like anti-estrogen therapy if the patient is HER2-positive and estrogen-positive. And then there are a lot of other different things we’re also using in HER2-positive disease after patients progress on that initial therapy, so there are what we call, antibody drug conjugates, where a chemotherapy like drug is attached to an antibody that then brings the chemo to the HER2-positive cell and allows for chemotherapy penetration more directly.

And then a class of drugs called tyrosine kinase inhibitors, which are oral drugs that get directed at HER2. So, another really exciting area to treat and a place where we’ve seen so many advances. And then in triple-negative breast cancer, I’d mentioned that chemotherapy has really been the mainstay of treatment historically because there weren’t great targets. But recently we’ve seen that immunotherapy, along with chemotherapy drugs like Keytruda, which you may have heard of.

Or atezolizumab, which is Mesenteric, can be used along with chemo and patients that overexpress a molecule called, PDL1. And that can actually include not just how long patients spend on the first treatment, but how long they live. So, we’re seeing a lot of triple-negative patients being great candidates for immune-based regimen now. And then for patients who have inherited a BRCA gene mutation, which many of you may have heard of. That gene mutation can actually predispose a triple-negative patient to be more receptive to a class of drugs called PARP inhibitors.

So, drugs like olaparib (Lynparza) or talazoparib (Talzenna) are new drugs that’ve been approved in the last couple of years in triple-negative metastatic breast cancer for patients who carry a BRCA1 mutation or BRCA2 mutation. And then there are also antibody drug conjugates in triple-negative breast cancer as well. The Trodelvy that’s been approved and then of course others that are in clinical trials currently. So, as you can see, it’s complex. I mean, the treatment of metastatic breast cancer is complicated. And so, it’s important I think to really be able to have a dialogue with your provider about what they’re recommending for you and why.

And I think there are often lots of options. And so, as much as you can make your doctor aware of what matters to you in terms of what side effects are you most afraid of or would you like most to avoid, what dosing schedules would be idea for your schedule for the rest of your life. So that you can deal with taking kids to school or the job that you’re currently working on or whatever, I think helps your doctor help you come up with the right regiment for you.

Katherine:

Yeah. Yeah. So, what factors are considered when deciding on the best treatment approach for an individual patient?

Dr. Meisel:

So, I think certainly the tumor type that we were talking about. Is it estrogen-positive or HER2-negative or HER2-positive? I think response to past treatments, both in terms of if someone has had metastatic disease for a long time and has had a few treatments already, how long did they respond to those treatments and how completely did they respond to those treatments. Did they have stable disease for a while or did their cancer actively shrink?

And then I think other than that, it would be some of the things I touched on. Side effect profiles. Do patients have pre-existing neuropathy from other chemotherapy? If so, maybe you want to avoid a regiment that causes more neuropathy. Schedule. Some patients, it’s really important to be on a certain schedule, as opposed to a different schedule. I think whether there are clinical trials available instead of whatever the standard of care regiment would be is also important.

Because for some patients who are interested in pushing the envelope or who might be a great candidate for a particular trial, if there is one that they’re a candidate for that’s not horribly inconvenient from a logistics standpoint, then trials I think are also a great option to consider. So, I think from an effectiveness standpoint, you want to think about the tumor type response to past treatments. And then potentially, if the patient has had, what we call genomic profiling, where the tumor has been sent for basically genomic analysis, to see what genes might be mutated in the tumor that could potentially drive a response to a newer, different therapy.

All those things can be taken into account as we think about the cancer. But then there is the patient specific factors, and I think those would be mainly side effects, schedule, clinical trials and desire or not to pursue those. And then, just what the patient’s perspective is on the plan that you’re offering them.

Katherine:

What is biomarker testing and how do results impact treatment options?

Dr. Meisel:

Great question. So, I think people often confuse germline mutations and somatic mutations. So, I’ll talk about that a little bit as we talk ab out biomarkers. So, I think biomarkers in general are factors within the tumor that allow us to make treatment decisions. So, if a biomarker in the tumor can predict response to a certain type of treatment, we want to know what that biomarker is so we can better treat the patient and more elegantly design a regimen. So, for example, having an estrogen-positive tumor, estrogen positivity is a biomarker suggestive of response to anti-estrogen treatments, which is why we give anti-estrogen therapy to ER-positive breast cancers.

But more recently, we’ve been able to move a little bit beyond estrogen, HER2- and triple-negative as our subtypes and think a little bit more in some patients about more sophisticated biomarkers. And that’s where somatic mutation testing comes in. So, there are germline mutations, which are inherited mutations that’re present in every cell in your body. So, for example, if your mother was a BRCA mutation carrier and based that BRCA mutation down to you, you would have a germline BRCA mutation. So, your cancer would carry a BRCA mutation, but so would every other cell you have.

And that’s a biomarker. That would make you a candidate for something like a PARP inhibitor. But in cancers, which the genes in the cancer have gone awry by definition, there are often other biomarkers within that tumor that may make you a candidate for certain treatments. And so, those mutations that arise in the cancer itself are called, somatic mutations. Those are mutations in the tumor, can’t be passed down to your offspring or anything like that and were not inherited by your parents. But mutations that’ve accumulated over time as these cancer cells have gone awry.

And so, genomic testing, or biomarker testing can be done often on a metastatic specimen. So, to be specific about it, say you had a metastatic breast cancer to the liver. You could have a liver biopsy done and that tissue from the liver biopsy could be sent for genomic testing. There are a lot of companies that do this and there are also some larger cancer centers that actually do in house testing for genomics. So, this testing can be done and what it does then is, it helps you determine, do you have a biomarker that predisposes you to a certain treatment.

So, if that metastatic liver tissues, for example contained high levels of PBL1 expression for example and you were triple-negative, that would say to your doctor, “Ooh, this is a great candidate for immunotherapy along with chemotherapy.” Or if you’re estrogen-positive, for example, and your tumor contains a mutation in the gene called PIK3CA and that might make you a candidate for a drug called, alpelisib (Piqray). So, these mutations could often be paired to a drug or treatment options, or sometimes to a clinical trial to allow patients to come take advantage of more targeted therapies.

That sometimes, because they’re targeted, have fewer side effects than drugs that are a little more discriminate.

Katherine:

Marie sent in this question prior to the program. Are there some genetic tests that’re more accurate than others?

Dr. Meisel:

That’s a good question. I would say most genetic testing platforms have been heavily vetted and approved by national organizations and laboratories that’ve been tested multiple times before they’re allowed to be marketed. So, I wouldn’t say that one genetic testing program is necessarily better than another. I think that any of the commercially available platforms that’re used are probably pretty accurate.

Katherine:

Okay. How does symptom management play into the treatment decision?

Dr. Meisel:

I was just going to add one thing to that, if that’s okay. I was going to say that I think it’s important when you’re using genetic testing platforms though to know what you’re testing for. So, there are some platforms that will just test for say, the three most common mutations in BRCA1 and BRCA2 that Ashkenazi Jews have.

And so, if you get that testing back and you’re negative, you might think oh, I don’t have a mutation in those genes. Well, we know from that testing, just as an example, is that you don’t have a mutation in those three alleles of that gene. But if you haven’t had full gene sequencing, you could have a mutation somewhere else in that gene. So, I would say all genetic testing that’s commercially available is probably pretty accurate. But it is important when you get testing done to know what you’re testing for and what you’re not testing for so you can interpret your results accurately. And genetic counselors, as well as your doctors can help you do that.

Katherine:

Right, right. Okay, I’m going to ask the question, this question again. How does symptom management play into the treatment decision?

Dr. Meisel:

I think symptom management is huge, because like I said and I tell this to all my patients at the outset of treatment that most of the time, metastatic breast cancer becomes a chronic diagnosis for a patient. You’re dealing with it, essentially like a chronic illness for the rest of your life. And you’re on some form of treatment for the most part, for the foreseeable future.

And so, making sure quality of life is as good as it can be is critically important. And I think symptom management is a huge part of that and we know that if we can treat and manage symptoms well, people can live better and often live longer because then they can stay on treatment for more extensive periods of time comfortably. And so, I always encourage patients, don’t be a martyr.

Don’t think you have to just bounce in here and tell me everything’s okay if it’s not okay. If you’re having symptoms and side effects from treatment, or from the cancer, I want to know about them so that we can really aggressively manage those symptoms just like we’re aggressively managing the cancer. A lot of times oncologists can do that on their own. We are pretty well versed in managing a lot of symptoms and side effects.

But a lot of times also, there are teams of doctors either who do palliative care or here at Emory, we call it supportive oncology where they are specially trained in things like pain management and managing more common side effects like nausea, constipation, diarrhea, appetite suppression, that can go along with cancer and with treatment.

And then they often will co-manage patients with us as well, just to make sure there’s that really strong focus on maintaining as much of a low symptom burden as possible.

Katherine:

So, you mentioned earlier, clinical trials. When should patients consider participating in a trial?

Dr. Meisel:

I think it’s a great question and I think the answer is really, almost any time. There are trials in every setting. So, I think one of the common misconceptions about clinical trials is that you really only should be in a clinical trial, or your doctor might only mention a clinical trial if they don’t have other options for you or if you’re really in stage. And I think that perception is changing. But I think the reality is that there are clinical trials in every setting.

So, we have clinical trails looking at prevention of breast cancer. Clinical trials looking to optimize early-stage treatment of breast cancer. Clinical trials looking at secondary prevention, so once you’ve had breast cancer, how can we reduce your risk of recurrence. And then lots of clinical trials in the metastatic setting both for patients who are initially diagnosed with metastatic breast cancer.

And then in second, third, fourth line and even for patients who have had tons and tons of additional therapy that we’re looking at new drugs for. So, I think at almost any juncture where you’re making a treatment change, it’s probably appropriate to say, would there be a clinical trail that you can think of that would be good for me in this setting? And it may be that there’s a one that’s 12 hours away, and it’s not convenient for you or feasible.

And it may be that your doctor doesn’t necessarily know of one but then that prompts them to ask a colleague who may be more involved in clinical trial design and development. Or it may be that there is one, but you ultimately choose not to pursue it because you have a different option. But I think it’s always appropriate to ask, would there be a trail for me? Because if there is, then maybe that opens up an option you hadn’t thought about before.

Katherine:

Sure. For patients who aren’t familiar with the stages of clinical trials, would you give us a brief overview of the stages?

Dr. Meisel:

Yeah. Absolutely. So, in terms of clinical trials that’re being done in humans, we talk about Phase I, Phase II and Phase III typically. So, a Phase II clinical trial is typically an earlier stage trial.

Looking at either a drug that has not been tested in humans before or a drug that has not been tested in a particular combination in humans before. And so, those trials are done only in select institutions, usually academic institutions as opposed to private hospitals. And they often have what’s called a dose finding phase and then a dose escalation phase. So, the earliest part of those trials is actually looking at, what is the safest dose to give to patients?

So, they start the first patients at a low dose of the compound. And if those patients do well, the next patients that’re enrolled get enrolled at a slightly higher dose. And then up until they reach the highest dose they can find where people are tolerating it and doing reasonably well. And in those Phase I trials, doctors and investigators are also evaluating efficacy, is this drug working. But the primary goal of the early phase trial is actually to find the right dose to then study in larger groups. And so, if they find the right dose and there’s good biological rationale for the compound, then the trial would go on to a Phase II.

Which might be just what we call single arm Phase II study, where every patient is getting that experimental drug. And we monitor them to see, is the drug effective, or is it less effective than the standard of care? Or sometimes they’re what we call, randomized Phase II trials where patients are randomized to either get the experimental drug, or to get what the standard of care would be in that situation. I think a lot of people get afraid about the idea of a randomized trial because they’re afraid they’re going to be randomized to a placebo. And that is really not done in the metastatic setting, because it wouldn’t be ethical to give a patient with active cancer a placebo.

So, usually the randomization would be either to the study compound or to a standard of care drug. And then if things look good in a Phase II trial, then a Phase III study is done which is usually what the FDA requires to allow a drug to go on and be administered outside of a study for approval. And those Phase III trials tend to be larger studies that’re done in larger groups of patients with more statistical validity because of their size, to determine, is this drug really better than the standard.

Katherine:

Right. We have another question we received earlier, this one from Eileen. She asks, how will I know whether my treatment is working?

Dr. Meisel:

That’s a really good question. So, I think for patients who have symptoms from their cancer, they often will know the drug is working because their symptoms improve. Say if you have lung metastases and you are short of breath and your shortness of breath gets better. That’s a really good sign that the treatment is working. I would say that often what we are doing, and it depends a little bit on the regimen and what the patient is getting and how often they’re coming in.

But we’re checking labs as well and sometimes there are lab abnormalities when a patient is diagnosed with metastatic cancer that can then improve over time. So, for example, if someone has a heavy burden of bone involvement with breast cancer, there’s a lab value called the alkaline phosphatases that will often be elevated. If that starts elevated and comes down, that’s a really good sign. And some of their liver function tests that we check and if a patient has liver metastases, we often will see those come down if a patient is responding.

There are also, what we call tumor markers that we can check in patients with metastatic breast cancer. Those would be proteins in the blood basically that can be made by the breast cancer in abundance. And those are called CA27-29 and CA15-3. Some doctors check both of them. Some will just check one depending on which one their laboratory at their institution is running. But typically, I will check those at diagnosis of metastatic disease. And then if it’s elevated, I know it’s a good marker to follow for my patient. And then I’ll follow that monthly or every three weeks, depending on when the patient is coming in to see me.

And if I see that marker start to go down, it’s not an absolute, but it can be a good early indicator of improvement with the treatment. And then I think it varies a little bit from practice to practice and based on patient preference. But often there will be scans done when a patient is initially diagnosed to determine the extent of the disease. So, usually a CT scan of the chest and the abdomen and the pelvis or a PET scan, which some of you may have heard of. Either one of those is good.

And that can be done about every 12 weeks usually in the beginning, to make sure a patient is responding and once you feel confident that they are, those can be done sell frequently. So, I would say the scans and the lab work and then the patient’s overall condition are usually the way that we look to see, are we having a response or not.

Katherine:

We’ve talked about several key tests. Some patients may be confused about whether they’ve received these tests. So, what questions should they ask their physician to make sure they’re getting appropriate testing?

Dr. Meisel:

I think it’s probably useful because not everybody needs every test, and I think there are often things you hear about online or from friends or even in a webinar like this, and there may be a good reason why you haven’t had that particular test. So, I wouldn’t assume that if you haven’t had everything that we’ve talked about today even, that someone’s made a mistake or that you need that and aren’t getting it. But I would ask. I think it’s always helpful to know more, knowledge is power. And so, if you have never had a CT scan or a CA27-29 level or a genomic testing.

I think it’s not a bad thing if you’re curious about it, to just ask your treating team, “Hey, I heard about genomic testing, is there a reason I haven’t had that? Or have I had that?” Maybe you have, and they called it something else. I think it is complicated, but I think it helps to understand what you’ve had done and what you haven’t had done. And sometimes, asking about something like that may prompt the team to do things that my benefit you.

Katherine:

Before we wrap up, Dr. Meisel, how do you feel about the future of breast cancer research and what would you like patients to know?

Dr. Meisel:

Yeah, I think one of the most important things and I actually said this to a family this morning where a loved one had received a new diagnosis of metastatic breast cancer is that the field has evolved so much over the past five years. I think often when people get a diagnosis of metastatic breast cancer, it’s the most dreadful feeling they ever had. They remember that day for the rest of their lives. But we are seeing so many people do so well for so long now and tolerate treatments well because the treatments are better tolerated.

And there’s I think more attention being paid now to symptom management. That people really can do so much better than they’ve been doing. And I would say really, every year, even every six months, when I go to give a lecture on a topic in metastatic breast cancer, I can’t just give the same talk. I’m always having to update my slides because there’s so many new things coming out, so much new research on the table.

And we’re seeing so many new drug approvals now that we’re starting to unlock some of these new mutations and reasons for progression and understanding new drug classes. So, really think it is a bright time to be in breast cancer research, and there’s never been a better time to be a patient if you have to fall into that category.

Katherine:

It all sounds so promising, Dr. Meisel. Thank you so much for joining us today.

Dr. Meisel:

You’re so welcome. Thank you for having me.

Katherine:

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. Also, don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs.

To learn more about breast cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell, thanks for joining us.

 

Where Do Clinical Trials Fit Into an AML Treatment Plan?

Where Do Clinical Trials Fit Into an AML Treatment Plan? from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang discusses the role that clinical trials play in advancing research, the benefits of participation in research, and explains why she recommends trials for AML patients. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

Where do clinical trials fit in when it comes to choosing treatment?

Dr. Wang:

Clinical trials are the mainstay of everything that we do in cancer care. Every single cancer drug that we’ve developed dating back into the 1970s at the National Institute of Health is the result of some patients and some doctors designing a clinical trial. These FLT3 inhibitors were developed over the last several years, so when I first came out of fellowship and started my training, we didn’t have these targeted therapies. Since 2017, in four years, we’ve had nine different drugs approved.

So, clinical trials are the way that we go from a finding in the laboratory to somebody having an extra birthday or going to their son or daughter’s wedding. That’s really how important it is, and those brave individuals who participate in clinical trials are helping not only themselves, but helping other people. I can’t tell you how many patients I enroll in clinical trials for AML, and I have told them – I said, “These nine drugs that we approved were because of nine different clinical trials which demonstrated benefit involving hundreds of thousands of patients.”

I can’t tell you how many times I’ve had a patient say to me, “Look, doctor, I’m going to participate in this clinical trial so that even if I’m not helped, you could learn something from me that could help the next person with their disease.” People are incredibly unselfish when it comes to clinical trials. I recommend a clinical trial for all my patients because I feel like that’s the cutting-edge clinical care.

I had patients here who I had on clinical trial drugs, and I was able to go to them and say, “Good news: Your drug has now been approved.” And, they say, “Doctor, why? I’ve been on this drug for a year.” And, I said, “That’s right, because you were part of that clinical trial, and you’re here now because of that drug, and now, a year or two later, that drug’s potency has been recognized, and now, the fact that you were in that trial has really helped us get this approval, which is going to help every other patient with that disease going down the line.” So, very important.

Shared Decision-Making, Advice for Partnering With Your AML Team

Shared Decision-Making, Advice for Partnering With Your AML from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang reviews how shared decision-making impacts overall care by keeping the individual patient and their unique circumstance in mind when determining a treatment path. Dr. Wang discusses the importance of reviewing clinical factors as well as having honest conversations, giving the patient a voice in their care. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

We’ve been hearing a lot lately about shared decision-making. In your opinion, how is this concept best put into practice?

Dr. Wang:

So, shared decision-making is the process where the physician is no longer dictating the care, and telling patients, “This is the best therapy for you,” and just plowing forward with it. Shared decision-making is really what we want in all of our relationships in our lives, which is sitting down and incorporating many points of view, including both the patient’s wishes and desires as well as those that he or she feels is important to his or her care.

It involves time. It does – it may involve multiple clinic visits. It involves sitting back and having the physician say, “This is the information, this is the data. What is important to you? What is going to work with your particular home situation and family situation and dynamic?”, and then, together, coming up with a decision about care that is individualized for the patient. We talked about individualizing the targeted therapy for the biology of the disease.

Shared decision-making is individualizing the treatment decision for the individual patient and their particular circumstance, and that is best done by sitting down with the patient, looking them in the face, not by looking at your phone, or staring at that computer screen, or reading off some diagnosis from a piece of paper. It’s really involving having those honest conversations.

That’s how things used to always be in medicine, is that it always used to be a decision where the doctor and you would talk and come to a decision, potentially. We’ve kind of gotten away from that with all the electronics and technology, and I think the shared decision-making is a conscious effort by individuals and groups to bring that back in case. It’s very important for AML. AML is a disease that affects largely older individuals, so if you’re in your 60s and 70s and 80s, I can tell you right now that each one of those individuals who have lived decades of life have a certain way that they want to live whatever time they have left.

Katherine:

Of course. Well, when considering a treatment plan, what key questions should patients be asking?

Dr. Wang:

They should be asking – it should be – they should be asking, “How is this going to affect my daily life?” They should be asking questions – “Do I have to be in the hospital? How – do I need to come to the clinic? If I have to come to the clinic, how many times do I have to come to the clinic?”

In my part of the world, it – sometimes even the season in which they’re being diagnosed can impact what disease treatment they want because certain times of the year, travel back and forth in different weather conditions can be difficult. They need to be asking not the question of – that we get asked a lot like, “What would you do if this was your father or your mother?”, but I wouldn’t know.

I turn that around and I say, “But, you’re not my father and you’re not my mother, and if you were my father or my mother, I would ask my father or my mother, ‘What is going to work for you? What are your goals? Do you want aggressive therapy? Do you want to go for high risk/high benefit, or do you want something that’s just going to make you be able to be outpatient for longer, and really what is the most important thing for you and your family right now when we look ahead as to the treatment path?’”

Katherine:

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

Dr. Wang:

It’s important for them to have a voice in their treatment decision because it is their – first of all, it’s their life, it’s their body. They are the ones that are going to be getting the therapy, suffering the consequences, and making the decisions that can impact not only them, but their loved ones, so – and, I find that the more they understand the disease process, the more they understand and can communicate to me their wishes, the more satisfied we are in care. I’ve had individuals tell me early on in the process where maybe, in a different patient, I would have suggested a second or third treatment – I’ve had them say to me, “I’m done. I’m not – thank you very much.” And, we all have to respect that.

It makes people more satisfied with their care. It makes people feel like they are making – they are guiding the path. They’re not just doing what their husband wants or what their doctor wants. I never want to have a patient say, “Well, I went and got chemo, Dr. Wang, because you wanted me to get chemo.” I don’t want you to get chemo, and I feel like if you have that understanding, I think patients are much more likely to pursue therapy and for the therapy, I think, to be successful or not. But, regardless of whether it’s successful medically, it needs to be successful emotionally for that patient and for that family.

AML Research and Emerging Treatment Options: An Expert’s Perspective

AML Research and Emerging Treatment Options: An Expert’s Perspective from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang shares exciting advances in the field of AML research, particularly in targeted therapies related to the TP53 and NPM1 mutations. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

What specifically are you excited about in terms of AML research and emerging treatment options?

Dr. Wang:

I am really excited about the advent of newer targeted therapies. Right now, we only have targeted therapies for probably about three mutations out of the many, many mutations that we know exist in AML. So, we know that there certainly are patients that have specific mutations, such as TP53 mutations, or patients who have very complicated series of DNA damage, that just don’t do well with any of our therapies.

I’m looking forward to another bunch of targeted therapies – these inhibitors called menin inhibitors – that might be useful for treating patients that have mutations in NPM1 gene or other chromosome abnormalities.

I’m also really looking forward to us being able to finally unleash the power of the immune system for treatment of AML with a few novel agents coming down the pike which have, for the first time, started to show that immune modulation can work in AML patients.

What Key Tests Do You Need Before Choosing an AML Treatment?

What Key Tests Do You Need Before Choosing an AML Treatment? from Patient Empowerment Network on Vimeo.

How do test results influence treatment choices for AML? Dr. Eunice Wang shares information about essential testing and explains how results aid in determining the best personalized treatment option for each patient.

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

What is the role of testing when deciding on treatment for AML?

Dr. Wang:

Testing is essential in us selecting and determining the best personalized treatment option for each individual patient. As you know, AML is an aggressive hematologic malignancy and can be devastating, both in its life-threatening nature and in its rapidity and the need for a rapid diagnosis. Testing, including both pathology results as well as protein marker testing, and, importantly in this day and age, DNA and RNA testing is essential because we have numerous different treatment options that could be available to the patient if their particular disease biology matches with the targeted therapies that we have.

So, as you may or may not know, since 2017, we’ve had eight or nine different therapies approved for AML, and this is a bonanza of options, some of which are only for specific biological subsets, and some even for specific patients, such as those above the age of 75. So, doing that testing, particularly that genetic testing, is important both in establishing the diagnosis and determining whether there is less toxic, more targeted, personalized treatment approaches, some of which involve low-dose chemo or even pills available to the individual patient.

Katherine:

You’ve answered this, in part, but which tests are essential following an AML diagnosis?

Dr. Wang:

I think all of them are essential, but in this day and age, for the selection of targeted therapy, it really is the mutational testing, which is looking at the RNA of the tumor cells and determining whether that has been altered in allowing the cells to express abnormal proteins. For standard chemotherapy, we also use DNA testing, which is looking at the different chromosomes and seeing whether there’s breakages or what we call translocations, pieces of chromosomes that have been swapped. That DNA chromosome information can give us some insight into prognosis and therapy response.

So, nowadays, it’s not just determining that you have acute leukemia, but looking at the specific DNA and RNA changes, and I have to say that this is a disease that we’re really not seeing any RNA or mutational changes occurring in more than 20 percent or 30 percent of patients. So all of the mutations that we see that could be impactful really don’t occur in more than 20 percent or 30 percent, and could only occur in five or one percent.

So, really, personalizing an individual patient’s disease, both for the disease biology as well as the person that’s getting the chemotherapy or the diagnosis, is really, really important.

Katherine:

Yeah. Let’s define a few terms that are often confusing for patients. What are biomarkers?

Dr. Wang:

Biomarkers are either proteins or expression levels on the cancer cells that can serve to tell us information about the biology of the disease. Okay, so, for example, if you have evidence of residual tumor proteins in your blood, that could be a marker, for example, of minimal residual disease, okay? And, that can tell you maybe one in a million cells have that biomarker, and then you can tell that those one-in-a-million cells are leukemia cells.

So, they’re any marker that we’re using that’s specific for the tumor that can help us in predicting or finding or locating or determining if a tumor would respond to a certain therapy.

Katherine:

What is biomarker testing?

Dr. Wang:

Biomarker testing can be done in many ways. For example, biomarker testing is drawing a sample from the patient and evaluating a marker that we think is going to predict for the disease type.

So, for example, in some cancers, we don’t want to biopsy the lung mass or the tumor mass every single time to see whether it’s shrinking, or getting smaller, or responding. So, in those patients, sometimes we’ll draw a blood sample, and we’ll look for a surrogate marker – some protein that’s expressed in the blood or some DNA or RNA in the blood that is a surrogate or a marker of the tumor so you don’t have to directly biopsy it.

In acute myeloid leukemia, we are looking for – like I said – particular cells in the blood that have particular proteins, and we measure those rather than going ahead and doing that bone marrow biopsy or biopsying those tumors. So, generally, in leukemia, it involves drawing blood samples – that’s the most common; it is a bloodborne disease.

Sometimes, we actually have to go into the bone marrow and do a bone marrow sample, but those biomarkers, as I said, can really improve our ability to detect very, very low levels of disease. So, for example, using a conventional bone marrow biopsy, we can only really detect 1 out of 200 cancer cells by normal – just by visual looking at, but by measuring biomarkers and mutations and other abnormal proteins, we can improve that to 1 in 100,000 cells.

So, really, these biomarkers are very sensitive and important because we want to detect the disease at a point where it’s very, very low. We don’t want to wait until the disease gets very advanced, in which case we think our therapies are less effective.

Katherine:

What is a genetic mutation?

Dr. Wang:

A genetic mutation is a mutation that occurs in the RNA of a cancer cell. That RNA dam – RNA aberration or abnormality does lead to different RNA – what we call transcript levels that lead to abnormal proteins.

Those proteins function in the cells to make a cell a cancer cell, okay? So, all cancer cells start out as normal cells, and as they acquire a mutation, they become a little less normal, and they start acquiring multiple mutations, and some of these mutations occur without DNA changes, some of them occur with DNA changes. And as these abnormalities occur, the cell gets more and more dysfunctional, and eventually, it starts becoming almost evil-ish.

It starts acquiring behaviors that are not normal, and then it starts to grow out of control, and that unchecked growth really is the end result of potentially many mutations occurring over time to drive that cell into becoming a cancer cell, and we call that process transformation, transforming from a normal, healthy-looking cell into almost a monstrous, cancer-like cell.

Katherine:

How do biomarkers affect AML treatment choices?

Dr. Wang:

So, those biomarkers, as I talked about, those mutations can determine what type of therapy patients can have. For example, up to 25 percent or 37 percent of newly diagnosed AML patients will have leukemia cells that carry the biomarker or the mutation in a gene called FLT3, or “flit.”

Those FLT3 cells can be inhibited by specific targeted therapies, including a drug called gilteritinib (Xospata), which is a pill which blocks mutant FLT3 expressed by AML cells. So, we’ve demonstrated, actually, in a randomized clinical trial that patients who have relapsed or recurrent AML who carry cells that have that biomarker – that FLT3 mutation – will actually do better if they take a daily pill – a FLT3 inhibitor – every single day for treatment of their aggressive acute myeloid leukemia than if we gave them low- or even high-dose chemotherapy in the hospital for four to six weeks.

So, that’s the power of those targeted therapies. Because the biomarker is telling you that there’s a sensitivity of that cancer cell to a specific blockage of that pathway, that can really dramatically change the course.

That is where the importance and the power of those biomarkers really goes into play. In the past, patients who had acute myeloid leukemia with FLT3 mutations did poorly with chemotherapy and had disease that came back even after multiple rounds of that intensive chemotherapy. The fact that we can give a pill and people could do better or even go to a bone marrow transplant off treatment with the pill is pretty remarkable.

Which AML Treatment Is Right for You? What You Need to Know

Which AML Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What should you know before deciding which treatment is best for YOUR AML? AML specialist Dr. Ellen Ritchie reviews key factors that guide treatment choices, including biomarker testing results, and shares advice for partnering with your team to advocate for the best care.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here: weillcornell.org/ekritchie.

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Expert Advice for AML Patients When Making Treatment Choices

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss how to access the most personalized AML therapy for your individual disease, and why it’s essential to insist on key testing. Before we meet our guest, let’s review a few important details. The reminder email you received about this program, contains a link to program materials. If you haven’t already, click that link to access information to follow along during this webinar. 

Finally, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. All right, let’s meet our guest today. Joining me is Dr. Ellen Ritchie. Dr. Ritchie, would you please introduce yourself? 

Dr. Ritchie:

Hello, my name is Dr. Ellen Ritchie, and I am an attending with a Leukemia service, and an assistant director since, for the last 15 years. 

And I treat mainly Acute Myeloid Leukemia, Myelodysplastic syndromes, which are kind of a pre-Leukemia; and Myeloproliferative diseases. And have a particular interest in the treatment of older patients with AML.  

Katherine:

Excellent, well thank you so much for joining us today. As we begin to talk about personalized therapy and AML, let’s start with the basics. How would you define personalized medicine? 

Dr. Ritchie:

Personalized medicine, to me is really, it’s a difficult question. It’s trying to find the best treatment for a particular patient. And it’s looking at biologic issues, what kind of cancer, what type of AML is it, what are the specific mutations or chromosomal abnormalities. But it’s also looking at the person. Is the patient active or not active? Do they have lots of other diseases like diabetes and coronary artery disease? Or pulmonary disease, or are they completely healthy? 

Or, do they have support at home? If they’re sick at home is there someone who can take care of them, versus a situation where you’re older and alone and you have no real family member to rely on. So, all of these things are very important in making a personalized decision as to how you treat a patient. 

Katherine:

Well, it sounds like, each person’s AML is unique. So, let’s help our audience be clear about basic testing. What tests are necessary to help understand a patient’s specific disease at diagnosis? 

 Dr. Ritchie:

I mean certainly it’s important to do a physical exam and to find out what the general health of the patient is. In order to evaluate an AML, or any other Leukemia, I look at the peripheral blood smear. To look at what I think the type of Leukemia might be that I am dealing with. There are some Leukemias that have particular way that they look like Acute Promyelocytic Leukemia for which there is a designated therapy which works.  

And you can tell that just by looking at a peripheral blood slide. The next test is always a bone marrow biopsy. Patients are not delighted that that is a test, but it is a test that can be done in the office, usually within 15 to 20 minutes. And that test gives us a lot of information. It gives us information about what type of AML it is, what are the markers on the outside of the cell, it gives us information about the chromosomes inside the Leukemia cell. Are there missing chromosomes, or rearranged chromosomes? And if there are, that can be very relevant to the prognosis. And lastly, it’s sent for a particular mutations or markers. So, we look for IDH3 mutations, we look for FLT3 mutations, we look for IDH1 and IDH2 mutations, and we do an entire myeloid panel. Which is about 44/45 genes that are most commonly mutated in patients with AML.  

So that’s the initial work up for any AML patient. 

Katherine:

You mentioned markers Dr. Ritchie. What is genomic, or bio marker testing? 

Dr. Ritchie:

So, we’re looking really at most specifically at mutations inside individual genes that might be in your Leukemia cell. So, there are some mutations actually that confer a better prognosis. Like NPM1 or CEPBA, those can be more positive type of prognosis than some of the others.  

But we’re also looking for markers that might be targetable with certain therapies that we have. So, if you have a FLT3 ITD or TKD, we actually have particular drugs which can target those particular mutations. There are also drugs that are FDA approved to treat IDH1 and IDH2 mutations. 

There are certain mutations that have a relatively poor prognosis, like TP53 for which there are clinical trials which are available, which specifically are meant to target patients who have those sorts of mutations. And there’re other clinical trials using the FDA approved drugs that I just mentioned, for FLT3, for IDH1 and IDH2 and combining it with other agents to try and improve outcome in AML patients. 

Katherine:

Some patients may not know if they’ve received these important tests, so what key questions should they be asking their physician about testing? 

Dr. Ritchie:

So, physicians, they – financial coverage of the mutational testing is not uniform across the country and across insurances. So, Medicare and different Medicare insurances and some of the private insurances all vary in their coverage.  

So, in my clinic, I am asking – I prefer the test that we do in house at Cornell. But it’s important that I ask, what will their insurance cover. And make sure that I send the appropriate testing that will be covered by insurance. There are some insurances that will not cover this type of testing. So, it is a real question for the patient, when you go to see the doctor to say, are you going to do mutational NGS testing?  

And, will my insurance cover this? Hopefully most – if Medicare adopts the coverage of these types of mutational testing, it’s often true that private insurance will eventually pick this up. But it’s a murky field and it’s really important to talk to your doctor about this. The cost of the bone marrow biopsy, and the chromosomal evaluation is nearly always covered by insurance.  

Katherine:

Okay, that’s really great advice, thank you. How do the results of these tests affect prognosis and treatment? 

Dr. Ritchie:

Well, when a patient has AML, if they are a fit patient, if it will help us determine after initial induction, whether to cure the patient we need to do a bone marrow transplant, or we can just continue with chemotherapy.  

And those are really important things to determine. So, if you have a good prognosis AML, if you have an AML that has certain translocations like inversion 16 or 821, or if you have a CEPBA mutation or you have an NPM1 mutation, and that’s all you have, you may do particularly well with chemotherapy treatment alone. And you won’t need to have a bone marrow transplant. 

If you have certain other mutations, we know that the only way that we’re going to cure you, is with a bone marrow transplant. And if you are fit, when we finish induction and even as we’re doing induction, we’re preparing you for a bone marrow transplant down the line.  

One disadvantage, just to mention about the molecular testing, is it doesn’t come back as quickly as some of the other testing. So that you will have already started induction chemotherapy most generally before the mutational testing comes back. Which can be anywhere – depending upon the institution, between seven and 21 days. So, it takes time for those results to be available.  

Katherine:

Outside of test results Dr. Ritchie, what other factors should be considered when choosing treatment? 

Dr. Ritchie:

So, you want to choose whether a patient is most likely to benefit from intense induction chemotherapy. With strong chemotherapies where the backbone of those therapies would be an anthracycline, like Daunorubicin or Cytarabine, or Daunorubicin or Idarubicin, together with Cytarabine. And these are intensive chemotherapies. Versus, non-intensive chemotherapy which is able to be done as an outpatient, more frequently. And it is something that is gentler for a patient, they’re less likely to have severe toxicity. And the backbone of those regimens is using a drug called Azacitidine or Decitabine, together with a second drug called Venetoclax. 

So, these are the two backbones, there may be clinical trials or there may be targetable aspects of your Leukemia, which drugs would be added to either of those backbones. But those are the two backbones. And I also like to identify those patients that may not benefit from chemotherapy at all. And so, it’s very important, I think to really get to know your patient. And I spend time with my patient, particularly on the first visit, to understand not only their physical health, but their mental health. How good is their cognition, what is their mood, are they depressed, or are they happy people? And what is their circumstance? Do they have people to support them? Do they live close to family? Is a caregiver able to come, with an elderly patient for example, to visits? 

Those, and whether or not they’re living alone and need tremendous support. So that’s really important to determine and helps me to choose what the best therapy might be. And also, concurrently what I can do to shore up the patient to do better with whatever therapy that I’m giving them. I.E., if you’re depressed, let’s work on that, or if your blood pressure is too high, or if you are – your diabetes is out of control at the same time that I’m seeing you, to try and fix those particular problems. In older patients I often do sort of a miniature version of the geriatric assessment. And in trials that have been so far, the most important aspects of the geriatric assessment, are really what is your cognitive function? Do have a mild dementia or do you not have a mild dementia? Because dementia may be or mild dementia may be associated with poorer outcome. 

The other is, are you able to do what we call the incidental tasks of daily life. So, you know fundamental tasks are really brushing your teeth and combing your hair, and dressing yourself. But are you able to do your cooking and your shopping and your banking and those things? Patients who have trouble doing their cooking and shopping and banking, and those types of activities, that also has been associated with a poor overall survival in AML. So, it’s really important to determine all of those aspects and if there are any deficiencies, to really know that the only therapeutic choice for that particular patient would be a low-intensity therapy. 

Katherine:

You touched upon this earlier, but what targeted therapies or treatments are available for AML patients? 

Dr. Ritchie:

So, there have been many recent FDA approvals of drugs that are targeted. One, is the FLT3 inhibitors. And the two that are available are Midostaurin, which is most commonly – was the first drug that was really added to intensive chemotherapy. 

And clinical trials show that in those FLT3 positive population that patients had an overall better outcome if Midostaurin were added to intensive chemotherapy. There’s also a drug called gilteritinib, and this drug is also a FLT3 inhibitor that was tested in patients who had refractory leukemia. They could either get real chemotherapy regimen or they could get gilteritinib. And it turns out in the FLT3-positive patients, the gilteritinib was superior to the strong chemotherapy. So that’s been approved for patients who have refractory, or disease that didn’t really respond to initial therapy, that is IDH – or is FLT3 positive.  

Then there’s the IDH1 and IDH2 inhibitors that have also been approved, and a small proportion of AML patients will be positive for IDH1 or IDH2 mutations. 

The IDH1 inhibitor Ivosidenib, is available and can be used to treat patients if you know up front, they have an IDH1 inhibitor. So, that’s a regimen where the single agent can be used to treat an IDH1 mutated patient who’s newly diagnosed. Those patients are also eligible for many clinical trials now, where they’re combining that particular drug with other agents, in an effort to improve outcome. For IDH2 positive patients, there’s a drug called Enasidenib. And this drug is used mainly in patients in the second line setting. But it specifically targets IDH2. And patients go into remission sometimes for a prolonged period of time. So, these drugs are FDA approved, and they’re treating targetable mutations.  

TP53 mutations are a particularly bothersome mutation because it confers a poor outcome. And I’m happy to say that we have clinical trials now that are available that actually target TP53 mutations.  

So, there are – there is therapy available for that type of mutation that was not available before through the clinical trials. And I expect in coming years that we’re gonna see more and more targeted therapies develop in AML which can be used potentially in combination with what we’re already using as backbones to enhance the outcome of patients with this disease. 

Katherine:

Well, how do targeted therapies work? 

Dr. Ritchie:

So, targeted therapies work on – it’s sort of complicated. The targets which are available, IDH or the FLT3 is really on the outside of the cell and it is a drug which is targeted directly to the FLT3 on the outside of the cell. 

It works quite well in the peripheral blood, where you see the blast oftentimes disappear. The big concern always is how well it’s working getting deep into the marrow. But it’s looking at the target on the outside of the cell. IDH1 and IDH2 inhibitors work on particular chemicals which are involved in the kreb cycle, and those of you that took high school chemistry may have memories buried in the deep parts of your brain of learning the kreb cycle. And this is a fundamental metabolic cycle inside cells, and if you have a mutation, an IDH1 or IDH2, you’re unable to go through that full kreb cycle in the appropriate way. And that is something that leads to you having a cancer, in this case AML. So, these drugs actually interfere with what’s happening in that kreb cycle, and allow you to make more normal cells. 

Katherine:

You mentioned earlier Dr. Ritchie, low-intensity therapy. Could you tell us about the types of treatment options? 

Dr. Ritchie:

So, I’ll go – high-intensity therapy or intense chemotherapy always has to be given really in a hospital. And if you don’t start it – if you can start certain intensive chemotherapies, like Vyxeos, which is also intensive, in the outpatient setting, but by day seven or eight, you end up in the hospital. And in intensive chemotherapies, you lose your hair, there’s GI toxicities, you’re at high risk of developing infections and you need a lot of transfusion. And for even young people, it’s a difficult therapy for which you’re in the hospital, and 90-some percent of patients are on IV antibiotics. 

So, it’s intensive chemotherapy because it has to be given in a hospital setting and requires intensive supportive care. Low-intensity therapy can be given in the outpatient setting. So, at the present time you can get a drug like Azacitidine, for example, which is an injection that you get seven days in a row. Unfortunately, you have to come to the doctor’s office every day for those injections, but once you’ve had the injection, you can go home. Combined with Venetoclax which is an oral agent. So, an oral agent can be given at home. You need close supervision in the physician’s office when you’re on this type of therapy, but you don’t need the constant support that you need if you are getting intensive chemotherapy. So, it can be done, in the comfort really of your home and with your family. You will have to come in and have transfusions potentially as an outpatient, nearly everyone does. And there’s always the risk that you develop a fever and if you do, you have to come into the hospital for IV antibiotics. 

But in general, low-intensity means not so much support needed in a hospitalized setting, and the tolerability of this particular chemotherapy in the outpatient setting.  

Katherine:

Once a patient has begun treatment, how do you monitor whether it’s working? 

Dr. Ritchie:

So, one of the more frustrating things about being an AML patient, is you don’t know right off the bat whether or not that you have gone into remission. So, what happens is you receive the chemotherapy, and the day you start chemotherapy is really day one. And somewhere around day 14, you’re at your lowest point. So, your blood counts are low, and you often feel really terrible, and you really wonder, is this working? But unfortunately, I can’t really tell you. Some institutions do bone marrow biopsies if you have intensive chemotherapy on day 14, or if you’re getting Venetoclax therapy somewhere around day 21 to look and see whether they still see Leukemia cells, but the utility of that is different per institution.  

The real test of whether chemotherapy x`, is at the end of about 28-35 days, are your blood counts coming up, and are you making normal blood cells. Are you making platelets, which are the part of the blood that clots the blood? Or are you making neutrophils, which are the important cells needed to help you fight infection. So, the real proof of a remission, is are your platelets over 100,000? Is your neutrophil count over 1,000? And when we look in the bone marrow around that time, do we see normal cells developing and no Leukemia? 

Katherine:

How often should testing take place? And should patients be retested over time? 

Dr. Ritchie:

So, the bone marrow biopsy is done frequently once you have a diagnosis of Acute Leukemia. So certainly, it’s done upon diagnosis of the disease. 

And as I mentioned earlier in certain institutions, about halfway through your chemotherapy cycle, they’ll do a bone marrow biopsy to see whether or not they see any residual Leukemia cells. That’s not done everywhere, and it’s done differently depending upon institutions sometimes. At the end of the chemotherapy treatment, if you recover your blood counts, we do a bone marrow biopsy to confirm a remission. If by day 35, we haven’t seen that your blood counts are recovering, we may do a bone marrow biopsy to see whether or not we see Leukemia cells in there, or early recovery. So, you’re definitely going to have bone marrows at those time points. If you’ve gone into remission, it depends on what we’d do next as to when you would have another bone marrow biopsy. So, if you’re going to bone marrow transplant you may have one more biopsy, just prior to going into transplant, and another biopsy at the end of the first month after transplant. 

If you’re gonna have what we call ongoing therapy, roughly every three or four months, we may do a bone marrow biopsy to determine whether or not the remission is holding. If during ongoing therapy, we see that there is blood count abnormalities that we weren’t expecting, that might be a reason that we would do a bone marrow biopsy. And that’s unpredictable as to when that would be.  

Katherine:

Dr. Ritchie, what advice do you have for patients to help them feel more confident in speaking up and advocating, being a partner in their care? 

Dr. Ritchie:

Well, when you choose a Leukemia doctor, you need to choose someone that you can actually communicate with. Someone who you feel is not allowing you to ask questions, or is not curious about what your life is like, you may wanna think, I wanna check out somebody else.  

Because it’s really important you like the person who’s your doctor, and that you have a trust relationship together. So, it’s really – I tell some patients it’s a marriage of convenience that we have. And that you really have to think of it that way. If someone doesn’t allow you to ask questions or if they are not fully answering your questions in a way that you understand, try and speak up for yourself and make sure that the doctor tries to address that. And if the doctor won’t address those things for you, or you feel like you don’t understand what is being explained to you, then you can think about trying to see someone else. I think it’s really important if you can, to write down as many questions as you have about your disease before you come in. 

Because often what happens is you get there, you’re stunned by the amount of information, and the questions you wanted to ask, you forget. And the next day, you’re like, ugh, I didn’t ask these questions. So, before you come in, if you write questions. Questions about insurance coverage, that may not be something that we go over. Or questions about toxicities, or questions, if I’m gonna lose my hair, do you have the name of a wig facility. All these questions that you might have, put them on a piece of paper, so that they can be addressed when you’re with the doctor. And other things will come up, you’ll have other questions when you’re there, but make sure your fundamental questions are answered. 

Katherine:

Yeah, those are great suggestions. We have a couple of audience questions. Mike wants to know, what does it mean to have high-risk AML? 

Dr. Ritchie:

High-risk AML means that there is something in your chromosomes that are worrisome and may confer a worse outcome. Or that one of the mutations that you have, or the combination of mutations that you have and the genetic testing are poor risk mutations that are associated with poor outcome. So, high-risk, really means a high risk of progression, or a high risk of – it’s a high risk of not going into remission and not being treatable AML. So, these are AMLs we treat aggressively, and if we get a patient into remission, we generally send high-risk patients to a bone marrow transplant. 

Katherine:

The second question is from Craig, he says; I’m currently undergoing treatment for AML, is the Covid-19 vaccine safe and effective? 

Dr. Ritchie:

I recommend the Covid-19 vaccine to everyone, all my patients. A little immunity is better than none. And there is preliminary data, looking at patients with Myeloid malignancies, not Lymphoid, but Myeloid malignancies, where it appears there is an immune response to the Covid-19 vaccine. So, I would suggest that you get the Covid-19 vaccine. Any of them that are available, are good. Whether it’s Moderna, or Pfizer, or Johnson and Johnson. Whatever is available to you, you should go ahead and get. 

Katherine:

Are there any symptoms or issues that AML patients should be looking for post-vaccine? 

Dr. Ritchie:

Post-vaccine, there’s a lot of symptoms that people have. And they can be similar among Myeloid patients. Some of my patients have had no reaction whatsoever, some people have had a really sore arm. 

Some patients are incredibly tired after the vaccine; some patients develop a low-grade fever for a couple of days. Those are really what we watch for. Sometimes when there’s a reaction, we’re hopeful that there’s an antibody being made, or an immune response that’s developing. So, it’s not always a bad thing if you have a reaction. But I don’t think that the reactions of patients of Myeloid malignancies is any different than that of the general public. 

Katherine:

That’s what it sounds like. To close Dr. Ritchie, what would you like to leave the audience with? Are you hopeful about the future of AML treatment? 

Dr. Ritchie:

I’m very hopeful. I’ve worked in this field for 15 years and through the 15 years we have seen a lot of new drugs that have been approved for AML. It’s remarkable, the FLT3 inhibitors, IDH1 and IDH2 inhibitors, new formulations of intensive chemotherapy, like Vyxeos, the Pfizer drug; glasdegib – I can never say that one. And most importantly, venetoclax, which has really revolutionized our treatment of low-risk, or not low-risk, but the low intensity patient. 

I see in the future that there is gonna be more – there’s an emphasis on immunotherapy, so I think we’re gonna see more antibody-based therapy that’s going to be approved by the FDA. Maybe it will be used in combination with the drugs that we are already using. There are all sorts of combinations using all the FDA approved drugs in different ways together. So, we can maybe do better with the drugs that we have. And there’s always new targeted drugs which are being tested in AML. So, I think as time goes on, from a molecular perspective it will be even more targeted. And I’m hoping also that there will be oral formulations of a lot of our drugs. So, it’s kind of exciting that there’s an oral form of Decitabine called Inqovi, which is something that could potentially be given in induction therapy right off the bat with Venetoclax for an all-oral regimen at home. 

All of these things are great advances, in my opinion, and I think that the opportunity to treat patients outside the hospital, with more targeted therapy and immunotherapy is gonna be the future. 

Katherine:

Yeah. And the future sounds promising. Thank you so much for joining us today Dr. Ritchie. 

Dr. Ritchie:

Thank you for having me. 

Katherine:

And thank you to all of our partners.  

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.

Treatment Approaches in AML: Key Testing for Personalized Care

When it comes to Acute Myeloid Leukemia (AML), genetic testing (or biomarker testing) is essential in helping to determine the best treatment approach for YOU. In this program, AML expert, Dr. Naval Daver reviews key decision-making factors, current AML treatments and emerging research for patients with AML.

About the Guest:
Dr. Naval Daver is an Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. More about Dr. Daver: https://faculty.mdanderson.org/profiles/naval_daver.html

Metastatic BC Research: How Can You Advocate for the Latest Treatment?

Metastatic BC Research: How Can You Advocate for the Latest Treatment? from Patient Empowerment Network on Vimeo.

What do metastatic breast cancer patients need to know about the latest research news? Dr. Megan Kruse shares highlights from the 2020 San Antonio Breast Cancer Symposium (SABCS), along with her advice for advocating for the right testing to help guide treatment options.

Dr. Megan Kruse is a Breast Medical Oncologist at the Cleveland Clinic. More about this expert here.

See More From INSIST! Metastatic Breast Cancer

Related Resources:

 

What Could Advances in Breast Cancer Research Mean for You?

How Can You Advocate for the Best Breast Cancer Care?

Factors That Guide a Metastatic Breast Cancer Treatment Decision

 


Transcript:

Dr. Kruse:                   

At this year’s San Antonio Breast Cancer Symposium, there were a few interesting presentations about the treatment of first-line metastatic triple-negative breast cancer that I think patients should be aware of.

Two of the presentations centered around trials that were presented in the past. Those reporting, patients reported outcomes from the IMpassion 130 study, which looked at chemotherapy for metastatic triple-negative disease plus the immunotherapy atezolizumab. And then, there was also an update on the results from the KEYNOTE-355 study, which was a study again of chemotherapy for metastatic triple-negative patients in combination with pembrolizumab, a different immunotherapy. And both of these studies showed that there was benefit for women in certain sub-groups of triple-negative breast cancer when looking at addition of immunotherapy.

And so, what I’d like to draw patients’ attention to with these presentations is that you have to be aware of if you fall into one of these categories so you know if you’re a candidate for the particular type of immunotherapy that can be added to chemotherapy. There are two different ways to test for if a patient is a candidate for immunotherapy and they are both tests that can be done on biopsies of metastatic or cancer recurrent sites in the body.

They can also be sent off of original breast cancer tumors. And what we now know is that for patients who do not have markers that suggest immune activation or where the immune system would be responsive to immunotherapy the addition of that extra therapy really does not help to improve cancer control over chemotherapy alone. And I think that’s a really important topic because everyone is very interested in immunotherapy, but it does have side effects of its own and it can actually be lasting side effects in terms of inflammation in organs like the liver, the colon, and the lungs.

And then, the third presentation that I’d like to bring up is the IPATunity study, which looked at the addition of a targeted therapy called ipatasertib to, again, chemotherapy for the first treatment of metastatic triple-negative disease.

And so, this is getting into an area of targeted therapy for metastatic triple-negative disease. And again, only looks at patients that have a particular marker that suggests sensitivity to this drug. And those are certain genetic markers, predominately changes in a DNA marker called PIK3CA. In this study, we actually found that there was no benefit for the targeted therapy added to chemotherapy for patients that had that genetic mutation, which was different than what was seen in earlier studies of the same combination. So, I think there’s more work to be done and it’s probably too early to say that this targeted therapy will not be used in treatment of metastatic breast cancer.

But what all of these research studies show together is that metastatic triple-negative cancer is not really just one disease. It’s very clear that within that one name, there are multiple different patient types and tumor types that need to be cared for differently.

And so, again, I think the theme from these abstracts and these research presentations is that we have to look into the right therapy for the right patient at the right time, which largely involved DNA-based testing.

So, when patients are thinking about their treatment options and how to best help with their providers about what treatment options exist for them, I think it’s important to recognize the type of testing that may be advantageous in your cancer type.

And so, for all metastatic breast cancer patients, we really recommend that they’ve had genetic testing to look for DNA changes like BRCA mutations that will lead to treatment options. For metastatic triple-negative disease, it’s important to make sure that you’re providers are testing for PDL1, which would make you a candidate for immunotherapy. And then, the more we learn about clinical trials, the more we have options for patients that have had drug-based DNA or genome-based testing. So, that’s an important term for patients to become familiar with is genomic testing.

And I think when you bring that up with your providers, they’ll know what you’re talking about and they’ll know that what you’re potentially interested in is new targeted therapy for the cancer that may either come in combination with chemotherapy or as a standalone treatment option. If you don’t have those options that are available, and FDA approved basis for regular routine patient care, there is always the option of clinical trials.

And so, if that is something that you’re interested in, genomic testing will often open the way. So, I think as you’re writing notes when you’re talking to your providers, you might wanna jot down whether or not you’ve had genetic testing and whether or not you’ve had genomic testing in the past, as both of those things will help potentially address all of your treatment options.

I’ve very hopeful about the research that is going to lead to new developments for breast cancer treatment in the next few years.

I think what we’ve seen both at this San Antonio Breast Cancer Symposium as well as other conferences in the recent past has been a lot of focus on finding the right treatment for the right patient at the right time. And so, patients seem to be very interested in finding out this information. They often come to clinic armed with the most recent data, which allows their providers to have really informed discussions about what the best treatment might be. And to talk about if the new treatments are not great right now, what treatments might look like in the future.

I think the other thing that’s encouraging about the research that we’ve seen presented at this conference is that some of these trials are very, very large. For example, the RxPONDER trial was a trial of over 9,000 patients. And I really think that’s amazing to get that many patients interested in research that may not directly impact their patient care but will impact the care of others moving forward.

It’s just a sign that our breast cancer patients are empowered, and they want to make a difference in the scientific community as a whole.

 

Breast Cancer Research News: SABCS Conference Highlights

Breast Cancer Research News: SABCS Conference Highlights from Patient Empowerment Network on Vimeo

Expert Dr. Megan Kruse shares highlights from the 2020 San Antonio Breast Cancer Symposium (SABCS). Dr. Kruse provides an overview of what this news means for early stage breast cancer patients, along with her optimism about the future of breast cancer research and treatment.

Dr. Megan Kruse is a Breast Medical Oncologist at the Cleveland Clinic. More about this expert here.

See More From The Pro-Active Breast Cancer Patient Toolkit

Related Resources:

 

Transcript:

Dr. Kruse:                   

The San Antonio Breast Cancer Symposium is a national meeting with international presence that combines all of the latest data from research on breast cancer topics. It involves clinical research, basic science research, a lot of patient, and patient advocate support.

And the idea here is to bring together all the different disciplines that are involved in breast cancer patient care and do the best information and knowledge sharing that we can each year.

This year’s San Antonio Breast Cancer Symposium brought us a lot of interesting research focusing on early-stage breast cancer patients. I think the most important presentations that were given had to do with the treatment of high-risk lymph node-positive hormone receptor-positive breast cancer patients. And these were really across three abstracts. The first abstract of interest was the Monarch E study, which looked at high-risk women with hormone receptor-positive HER2-negative breast cancer and optimizing their medical therapy.

So, these patients are typically treated with anti-estrogen therapy and the idea of the research that was presented was if the addition of a targeted medication called abemaciclib or Verzenio could help to improve outcomes for women in this population. And what the trial found was that for women who took their anti-estrogen therapy for the usual length of time but added the abemaciclib for the first two years of that anti-estrogen therapy that there is actually an improvement in cancer-free survival time or an improvement in cure rates. And this was important because these women may not benefit from chemotherapy, as we’ll talk about in another abstract.

An addition research presentation that was given that goes alongside of the monarch E study was that of the Penelope B study. And the Penelope B took a similar population to what was studied in Monarch E. So, again high-risk women with lymph node-positive, hormone receptor-positive, HER2-negative breast cancer; however, in Penelope B, all of these patients had received pre-surgery chemotherapy.

And in order to qualify for the trial, the patients had to have some cancer that remained in the breast or the lymph nodes that was taken out at the time of their surgery. So, these are patients clearly in which chemotherapy did not do the whole job in terms of getting rid of the cancer. And again, the idea here was to add a second targeted therapy to the endocrine therapy to see if that would improve cancer-free time for patients in this population. The difference in this study was that the partner targeted therapy that was used was a drug called palbociclib or Ibrance.

And the drug was actually only used for one year in combination with endocrine therapy rather than two years as was used in the Monarch E study with abemaciclib. Interestingly enough, the Penelope B study was a negative study, meaning that it did not improve the cancer-free survival time for women who took the endocrine therapy plus targeted therapy compared to women who took the endocrine therapy alone.

So, I think that these are two interesting studies that one should look at together. And clearly, may impact what we do for the treatment of high-risk hormone receptor-positive women moving forward. The third abstract that I’d like to touch on that I think was important for women with early-stage breast cancer is the RxPONDER study, also known as SWOG 1007. And this study again was looking at lymph node-positive, hormone receptor-positive HER2-negative breast cancer patients and seeing if the addition of chemotherapy helped to improve their cancer-free survival compared to anti-estrogen therapy alone.

And so, in this study, while the study population was all women with early-stage breast cancer, meeting the one to three lymph node-positive criteria, you really have to break the results down into the results for pre-menopausal women and the results for post-menopausal women.

Because overall the study really showed no significant benefit to chemotherapy on top of endocrine therapy for women in this population; however, we did see that there was a clear benefit for women who were pre-menopausal. So, the women who had no benefit from chemotherapy were largely those who were post-menopausal, while those who were pre-menopausal derived extra benefit from chemo on top of anti-estrogen therapy. And that benefit depended on what the Oncotype recurrent score was.

With women that had the lowest of the recurrent scores having a chemo benefit of about three percent going up to over five percent for women who had Oncotype recurrent scores in the mid-teens to 25 range. In both of these groups, women who had Oncotype scores of 26 or above would have chemotherapy as per our standard of care.

So, I think that this abstract is important because in the past women who had lymph node-positive breast cancer generally received chemotherapy no matter what. More recently we’ve understood that not all of these cancers are created equal and that some cancers may not actually have benefit from chemotherapy in terms of improving cure rate. So, this study is a big step forward to help individualize and specify the treatment for women with lymph node-positive, hormone receptor-positive, HER2-negative early breast cancer.

I’ve very hopeful about the research that is going to lead to new developments for breast cancer treatment in the next few years.

I think what we’ve seen both at this San Antonio Breast Cancer Symposium as well as other conferences in the recent past has been a lot of focus on finding the right treatment for the right patient at the right time. And so, patients seem to be very interested in finding out this information. They often come to clinic armed with the most recent data, which allows their providers to have really informed discussions about what the best treatment might be. And to talk about if the new treatments are not great right now, what treatments might look like in the future.

I think the other thing that’s encouraging about the research that we’ve seen presented at this conference is that some of these trials are very, very large. For example, the RxPONDER trial was a trial of over 9,000 patients. And I really think that’s amazing to get that many patients interested in research that may not directly impact their patient care but will impact the care of others moving forward.                                   

It’s just a sign that our breast cancer patients are empowered, and they want to make a difference in the scientific community as a whole.

 

Advocating for Key AML Testing: Advice From an Expert

Advocating for Key AML Testing: Advice From an Expert from Patient Empowerment Network on Vimeo.

Dr. Hetty Carraway, an AML specialist at Cleveland Clinic, shares advice on advocating for yourself when diagnosed with AML, underscoring the importance of asking questions, and including your caregiver as part of the conversation.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here.

See More From INSIST! AML

Related Resources:


 Treatment Approaches in AML: Key Testing for Personalized Care

 New AML Therapies vs. Traditional Chemotherapy: What’s the Difference?

 Understanding Risk in AML: How Molecular Testing Affects Treatment Options

Transcript:

Katherine:

What advice do you have for patients when it comes to asking for appropriate testing and speaking up in their own care?

Dr. Carraway:            

This is so important. I think patients are leery to stir the pot or be difficult. I think coming from a place of inquiry, teach me about this, that, or the other thing, help me understand this, that, or the other thing – I would like you to show me why this decision or talk with me about why this decision versus another decision might be better for me compared to somebody else.

I can’t underscore the importance of advocating for yourself and asking questions about why am I getting this drug? What are the side effects to this drug? What is my prognosis? What is different about my case versus somebody else’s situation? How do I best prepare myself in getting ready for the therapy that I’m about to go through?

Those are all important questions that patients should ask. They should certainly have people, if possible in their family be advocates for them. I welcome that, and I think that that’s a really important part of going through this type of therapy for any patient. Your physician should welcome having your involvement in that. Don’t be shy about that. It’s your health, and any investment in that the most important people in that is inclusive of you and your caregivers. They should be a welcome part of the team.

Understanding AML Induction and Consolidation Therapy

Understanding AML Induction and Consolidation Therapy from Patient Empowerment Network on Vimeo.

Dr. Hetty Carraway, an AML specialist at Cleveland Clinic, provides an explanation of the role of induction and consolidation therapy in AML patients.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here.

See More From INSIST! AML

Related Resources:


 Treatment Approaches in AML: Key Testing for Personalized Care

 New AML Therapies vs. Traditional Chemotherapy: What’s the Difference?

 Understanding Risk in AML: How Molecular Testing Affects Treatment Options

Transcript:

Katherine:

Would you define induction therapy and consolidation therapy and tell us what the differences are?

Dr. Carraway:            

For most patients that are diagnosed with an acute myeloid leukemia, over the last 30 to 40 years we’ve used an intensive chemotherapy regimen that we call induction. Induction means that we’re trying to get the leukemia into remission with an intensive chemotherapy regimen. Classically, that has been two agents; one, a cytarabine based regimen along with an anthracycline, either idarubicin, danorubicin, or some anthracycline that’s similar.

Now, the cytarabine based therapy is a continuous infusion over seven days. The anthracycline is given over three days as an intravenous IV push, and so that’s why it’s kind of been nicknamed seven and three – seven days of cytarabine and three days of another anthracycline.

Now, that has constituted the induction intensive regimen in the hospital with the idea that that leukemia gets under control and goes away. More recently for patients, they can receive therapy that is not this inpatient, in-hospital, induction chemotherapy but rather use oral therapy combining with venetoclax, which is a Bcl-2 inhibitor, along with azacitidine, which is either IV or subcutaneous given to patients over seven days. The oral, venetoclax is every day.

That type of induction can also be given and is now an outpatient regimen and more often offered to patients that are older, over the age of 75.

That, too can be considered induction with the idea that once a patient is diagnosed with leukemia this regimen is started, and after one month or even two months on venetoclax plus azacitidine patients’ leukemia can get into what we call remission, where the blast percentages are less than 5 percent. Then, normal hematopoiesis of platelets being greater than 100,000 and a neutrophil count greater than 500 or 1,000, and the patient is then transfusion-independent.

In general, induction chemotherapy is that first round of chemotherapy that’s trying to get the leukemia under control.

Consolidation chemotherapy is when you use subsequent cycles of chemotherapy to keep the leukemia under control because we know that if we don’t continue to give some continuation of therapy that the small, little seeds of leukemia will re-emerge and leukemia will relapse.

Essential Testing in AML: How Results Impact Care & Treatment Choices

Essential Testing in AML: How Results Impact Care & Treatment Choices from Patient Empowerment Network on Vimeo.

What tests should follow an AML diagnosis and why? Dr. Hetty Carraway, an AML specialist of Cleveland Clinic, reviews the essential testing for patients with AML and explains how those test results may inform treatment decisions.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

What Is the Patient’s Role in Making AML Treatment Decisions?

What Is the Patient’s Role in Making AML Treatment Decisions?

Navigating AML Treatment Decisions

Insist! AML Resource Guide

Transcript:

Katherine:      

Hello, and welcome. I’m Katherine Banwell. Today, we’ll discuss how you can be proactive by insisting on better AML care and personalized treatment options. Joining me is Dr. Hetty Carraway.

Welcome, Dr. Carraway. Would you please introduce yourself?

Dr. Carraway:            

Hi. My name is Dr. Hetty Carraway. I’m one of the physicians at the Cleveland Clinic. I work as the Director of the Leukemia Program, and I spend most of my time caring for patients with acute leukemia and bone marrow failure states.

Katherine:                  

Thank you.  Let’s start with the basics. What essential testing should AML patients undergo following a diagnosis?

Dr. Carraway:            

This is a pretty standard workup for patients that have this diagnosis of acute leukemia.

For most of our patients we always evaluate with a peripheral blood count including a complete blood count with differential, typically a comprehensive metabolic panel, and looking at a test called a uric acid, which looks at the cell turnover and the cellular debris in terms of the burden on the kidney. We often will get a bone marrow biopsy with aspirate for patients, and in the diagnosis of leukemia typically that’s already been done.

There are tests that are sent off of that aspirate called a test for chromosomes, whether it’s comprehensive cytogenetics or FISH, for fluorescence in situ hybridization. We’re often testing using a study called NGS or next generation sequencing looking for specific mutations of genes known to be important in the pathogenesis of leukemia.

Furthermore, we often get a test called flow cytometry from that aspirate looking at the markers on top of the leukemia cells that help us to identify the blast population. So, I would say those by and large are the tests in the bone marrow biopsy that we get, which are innumerable and detailed.

They often take some time to get back, so at the time of the diagnosis patients know that they have a diagnosis of leukemia, but those additional chromosome tests or mutation testing that can take up to two weeks if not longer to get back. And so, it’s important to follow up on that information later on and say, has that testing come back? If so, how does that change any of what the decisions are moving forward?

Katherine:                  

Genetic testing can often be confused with molecular testing. What’s the difference between the two, and why should patients undergo the testing?

Dr. Carraway:            

The chromosome testing and the mutational testing help us to really classify the risk in terms of the leukemia itself, whether or not that leukemia is responsive to chemotherapy alone, or if it means that there’s a higher likelihood of that leukemia not being controlled with leukemia only.

In that setting, we often then move towards transplant for curative intent in addition to the chemotherapy. The reasons to get the information is to really help us better tailor the therapy for each individual patient. That information really does help us guide not only the upfront therapy for some patients but even the long-term therapy. It can be incredibly overwhelming to have too much information at the get-go, so in some senses it’s better to have these pieces as they unfold over time.

For other patients, they want to know what exactly the plan is going to be A to Z from day one. That is of course more challenging now that it just takes time to get this information. I think what they need to know is that we’re working hard to get that information.

As soon as we get it, we don’t hold back. We reveal and share that information and come together to say, this is what this data or information means, and these are some of the choices that we either recommend that you consider, and these are the risks and benefits to those considerations.

Katherine:                  

Let’s look at something that is similar to what you’ve just been talking about. How do test results impact treatment and overall care?

Dr. Carraway:            

They really can. When you asked me how come chromosome or genetic information is different than mutational information, the chromosomes can help us to figure out where patients land in terms of prognosis. That information is different than the mutational testing. Both of those pieces can help us figure that out.

The mutational test, I will tell you, does help us figure out are there targets on the leukemia that allow us to use therapy that’s directed to that mutation. The key example I’ll give is a mutation in a gene called FLT3. That particular mutation has an agent now that is F.D.A. approved called Midostaurin, and so once we know that a leukemia harbors a FLT3 mutation we often add a drug called Midostaurin to the backbone therapy that is used for patients.

Now, that’s important, and now there are more and more genes that when mutated we have novel therapies that direct against that specific tag that’s on the leukemia and helps to improve eradication of the disease or control of the disease if you will.

That’s different than the genetic information when we’re looking at chromosomal changes that may allow us to say in the rare instances of  favorable cytogenetics like a translocation of chromosome 15 and 17 consistent with APL, the treatment for that type of leukemia,  acute promyelocytic leukemia, is very different than what we do for the majority of other leukemias.  

The prognosis for that leukemia is also very different. It helps to tailor the regimens, and it helps to select specific therapy that may be helpful to each individual patient.

Katherine:                  

Dr. Carraway, you just mentioned FLT3. Would you tell us about the common mutations in AML and how these may impact treatment options?

Dr. Carraway:            

There’s a multitude of mutations that we’re now following in patients. The way that we follow them is by doing this next generation sequencing test at the upfront time at diagnosis.

The reason why we’re doing that is because those mutations can regress with therapy, or they can progress where you gain additional mutations that happen as the disease progresses. Even if it’s responding to therapy or as it loses response to therapy and reemerges, it may reemerge with different mutations. As a result of that, it may change what therapy we select. Our ability at this point in being to recommend exactly at what time points we are checking the next generation sequencing we’re still learning right now as to what are the key times to do that testing.

In general, most institutions are doing that next generation sequencing at the time of diagnosis, and then also for some patients before they go to bone marrow transplant and even after bone marrow transplant.

For some of those patients that unfortunately relapse, we’re also making sure to retest the next generation sequencing mutation testing to see are there new mutations that have come about that weren’t there before?

Katherine:                 

I understand there’s something called IDH. 

Dr. Carraway:            

You were also asking about what other mutations besides FLT3 happen in patients with AML. FLT3 is one such mutation. NPM1 is another mutation that often it frequents patients that have AML. Those two mutations happen in about 30 percent of patients with AML. There are other mutations such as DNMT3A, ASXL1, and TET2 that we typically see in patients with MDS or even a pre-leukemia state called CHIP. For other patients, we have mutations that are targetable like IDH1 or IDH2.

Those two mutations happen in probably 10 percent to 15 percent of patients diagnosed with AML. Why are those important? They’re important because we have oral medications that are pills that patients can take. In the relapse setting for many patients after induction or intensive chemotherapy, they can use these oral therapies to try and control their leukemia. These are pretty exciting. 

All of these oral therapies have been approved in the last two to three years in the space of leukemia, so it’s been a game-changer in terms of identifying these mutations and then identifying drugs that target those mutations. It’s really changed the landscape for patients with AML. It’s new information, and that’s why as patients you want to hear about this so you know what questions to ask and you know, can you tell me, am I a candidate for one of these oral medications that is now available for patients with AML?

Katherine:                  

Dr. Carraway, thanks so much for joining us today.

Dr. Carraway:            

Thank you for the opportunity to be here. 

Katherine:                  

And thank you to our audience. I’m Katherine Banwell.