Some patients fear that clinical trials may be too experimental and risky. Dr. Martin Edelman outlines the clinical trial process and addresses myths surrounding trials. Want to learn more? Download the Program Resource Guide here.
Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.
Here’s the last one that I have on my list here. Clinical trials are experimental and risky.
Yeah. Well, so is the rest of life. So, there generally – is there risk? Yes. Essentially, every patient is always a trial because we for the most part don’t – even in the disease states where we have very active treatment – so, let’s say – for example, we were talking about the EGFR mutation. So, we have excellent drugs. We have a drug now, osimertinib – outstanding drug, easy to take, low risk of side effects.
The earlier generations – there was a lot of rash, diarrhea. That’s been pretty much done away with. But on average, patients benefit from this drug for about a year and a half.
So, that’s not great if you’re 40 or 50 years old. You want to do better. So, what are our current studies? Well, we’re looking – we’re re-addressing a question that we thought had been answered, but really it wasn’t – about, well, what’s the value of chemotherapy plus this drug? What about the value of other drugs?
So, we can’t promise anybody anything, but our current treatments are still not good enough. There are certain diseases, let’s say Hodgkin’s disease, where you know you’re gonna cure almost all the patients up front or testicular cancer, etcetera, where – again, but thanks to trials, clinical trials, we now are at that stage. We’re not there yet in lung cancer, and the reality is is every patient should really be on a study. I think it’s – and we have this problem now in that our studies have also become far more complicated to enter people in because there are many more variables one has to look at it. What’s the molecular background of the tumor? How many prior therapies?
The condition of the patient, their organ function, etcetera – and the regulatory burden has become much, much greater. But clinical patients are in clinical trials. Let’s look at the question. Are they risky? Well, everything is risky, but we do a lot to manage that risk. Patients who are in studies are observed more closely. We have to. It’s the law. There’s frequently additional personnel assigned. They’re usually getting standard of care plus a new treatment or a new treatment followed by the standard of care or some variation of that.
They’re observed, like I said, much more carefully than we would otherwise. And so, I think actually patients on trials generally will do better, and we actually have evidence. Multiple individuals have looked at this – everything from first-in-man trials or early dose escalation studies, controlled studies – that show that patients, even those on the control arm, generally do better than similar types of patients who are not treated on studies because we just are more careful.
And the physician who participates in trials is generally someone who has a greater knowledge of the disease.
https://powerfulpatients.org/pen/wp-content/uploads/Are-Clinical-Trials-Too-Risky_-A-Lung-Cancer-Expert-Reviews-the-Facts.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 16:33:162020-02-10 10:04:04Are Clinical Trials Too Risky? A Lung Cancer Expert Reviews the Facts.
Let’s talk a little bit about some of the concerns that patients have about the side effects. Let’s see: Side effects are unavoidable.
Well, that’s not true. As I said, what were the side effects? If you go back a couple decades and you ask patients what were they concerned about, many of them were concerned about nausea and vomiting. And that is largely a thing of the past. Many patients will still have some queasiness with treatment, but even our most nausea-producing drugs – we really do have outstanding drugs for the prevention of that. You have to use them. You have to take them.
It’s very important to give them appropriately. There are very excellent guidelines that are out there. Sometimes, patients are still undertreated, no question about that. Not every drug has industry strong backing. There’s one drug – for example, olanzapine, (Zyprexa) was actually developed as an antipsychotic, and I always tell the patients, “No, I don’t think you’re crazy.”
But it’s at a lower dose, and we have excellent, excellent evidence that that drug given for a few evenings after chemotherapy is extraordinarily effective along with the other drugs in preventing nausea and vomiting. So, that’s one thing.
Hair loss is still somewhat inevitable with certain drugs – the taxanes. But many of our regimens don’t cause hair loss.
Or as I tell folks – only you and your hairdresser will know for sure because its hair on the pillow, but the average person won’t pick you out of a crowd. Those are big concerns still. There still are potentially life-threatening effects from chemotherapy, and we spend a lot of time educating people about that. But those are not inevitable, and it’s actually a minority of patients in lung cancer.
One should not confuse – there are different malignancies. Still, the treatments for say leukemia, though even that’s changing, can be extraordinarily toxic or the bone marrow transplant patients. Many, not just lung cancer, but in the other diseases as well – many of the things that people attribute to the drugs are more due to the disease. So, I always say, “The greatest failure and side effects to the drugs are they don’t work well enough because the side effects of the disease can be considerable.” So, that’s the bigger issue. The immunotherapeutic drugs have a rather interesting set of side effects.
They are clearly initially or frequently better tolerated than the older cytotoxics, which still have an extremely valuable place in the treatment and cure of lung cancer. The immunotherapeutics have clearly been quite beneficial, but their side effects can be subtle and far less predictable and can be very severe. Virtually, any organ in the body can be affected by this. We like to say, “If it ends in ‘itis,’ you can get it from immunotherapeutics.”
So, there are lots of side effects, no question. But they can be managed. They can be prevented. They can be treated. Sometimes, we have to abandon a drug. So, people who get severe – what we call immunotherapy-related adverse events – may not be able to continue on their drugs. But even that is not necessarily always the case.
This next one really gets to the heart of the doctor-patient relationship.I shouldn’t share my side effects with my healthcare team because I don’t want them to stop my treatment routine.
Well, you can’t prevent the side effects if you don’t know about them. And I always would tell patients, I said, “You know, if you’re having a problem, please don’t call me at 4:00 on Friday afternoon. I’m gonna end up sending you to the emergency room, which I may anyway.” But a lot of times, we can solve certain things over the phone. There are a lot of side effects that can be treated and particularly if one is aware early on. So, yeah, you should share the side effects because how’s somebody gonna know how to deal with them?
Now, the problem we run into sometimes is in a population that’s on average 60s and 70s, could be younger. There’re lots of things that can be just part of ordinary life. Everybody gets headaches, back pain, etcetera, etcetera.
We have to treat those sometimes and evaluate them much more aggressively because of the possibility of them being related to disease or drug, but it helps to sort it out. You can’t be too blasé about it because sometimes things need to be looked at very urgently, particularly with immunotherapeutic drugs. Some of the side effects that can be severe can sometimes be very subtle in their onset.
https://powerfulpatients.org/pen/wp-content/uploads/The-Truth-About-Managing-Lung-Cancer-Treatment-Side-Effects-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 16:26:122020-02-10 09:59:49The Truth About Managing Lung Cancer Treatment Side Effects
Let’s talk a little bit about health literacy. What would you suggest patients use for online resources? What are good resources?
So, there are some excellent resources. The International Association for the Study of Lung Cancer has resources for patients. The National Coalition of Comprehensive Cancer Center Network (NCCN) has resources. American Society of Clinical Oncology has resources. So, those or American Cancer Society. So, there are some really reliable sources out there. And there’s a great deal that’s very unreliable – people’s Facebook pages. I’ve seen this.
It’s a big place.
Everybody always – and I think it’s important for people to understand. There will be people who will get something and have a fantastic response. I’ve used anecdotes.
The anecdotes I’ve used are to illustrate the potential hope of benefit. They’re not exceptions to the rule anymore. They’re the good case scenarios. I could have just as many anecdotes of people who didn’t benefit and stuff. And I think it is important going into this – and that’s why we are reassessing patients constantly and getting repeat scans because we don’t necessarily know always – even if something’s 90 percent effective, it means 10 percent of the time it’s not.
And each patient – we’re getting better at individualizing and personalizing therapy, but we’re not perfect yet. And we probably never will be. So, there will always be anecdotes. I think what’s – as a friend of mine puts it – the plural of anecdotes is not data. When I say, “Well, chemoimmunotherapy works.” It’s not because I have anecdotes of that, though anecdotes illustrate the magnitude of benefit.
I have data that shows that the chemoimmunotherapy regimen was compared to chemotherapy and was clearly and unequivocally superior. When I give a statistic that 60 percent of patients, 65 percent, can benefit from those types of regimens. That’s based upon prospective randomized control trials.
https://powerfulpatients.org/pen/wp-content/uploads/Trustworthy-Resources-to-Help-You-Learn-More-About-Lung-Cancer-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 16:16:092020-02-10 10:05:05Trustworthy Resources to Help You Learn More About Lung Cancer
How about this one? Treatment is not effective in older patients.
Treatment is highly effective in older patients. It’s interesting. So, we had long arguments about, when I started in this field, whether treatment ever worked, and there were a number of studies that showed that chemotherapy – that one platinum was better – what’s called a platinum-based agent – was better than no therapy.
And then that two drugs were better than one drug. And people would say, “Oh, well, that doesn’t work in the elderly. And they should only get one drug.” And that’s because, I guess, their burning bush on the lawn told them this. And the fact is is that then got evaluated in a controlled trial, a very nicely done study by my European colleagues. But what was crucial was that they used somewhat lower doses of chemotherapy, a little bit different schedule of chemotherapy, and it was clearly superior to a single agent. And those were even days before immunotherapeutics and these targeted agents. So, many patients will benefit. You just have to be aware of certain basic principles in geriatric medicine as well as basic principles of lung cancer care.
So, first off, if the patient is elderly but their tumor is characterized by a driver mutation, they get one of the so-called targeted agents. And these are these days very non-toxic, easy to take, and highly effective.
Patients – many are going to be eligible for immunotherapy either as a single agent or combined with chemotherapy. Chemotherapy drugs could certainly be cut in their doses and still preserve much activity and be done safely.
I had a woman with small cell lung cancer. This is now about a year and a half ago or so. And she’s in her 80s. And she came to me because she was told – oh, just sorta get your affairs in order. And her disease was what we term an extensive small cell. The staging system’s a little bit different, but she didn’t have a really vast bulk of disease. And we treated her with standard chemotherapy drugs but at somewhat lower doses and some careful TLC and some other supportive things like growth factors.
She got all of her treatment on an outpatient basis, had an excellent response. We used radiation later to consolidate her treatment, and I see her back every couple of months. I wouldn’t say that she’s necessarily cured of her disease, but she does yoga every day. She lives a full life. She sees her grandchildren. And she’s, I think – I wanna say 83-84 years old. I think she’s quite grateful for that. It’s not the numerical age.
The flipside is if somebody’s 50 years old and they’re extremely ill when they come in, then one has to be very cautious about what one does. We used to say that those patients who come in who are severely impaired should simply get supportive care and hospice services.
And actually, how would I put it? Our lives have gotten a little bit more difficult lately because as things have gotten better for patients – because I can’t necessarily say that as much because some patients may be very susceptible to the effects of – their disease may be very susceptible to the effects of immunotherapy. I had one patient who was a younger gentleman who was on a gurney. He was in his 50s, lost an enormous amount of weight , he was on oxygen. We immediately gave him fluids. My fellow – I had an excellent fellow at the time – came to me and said, “Should we admit him and send him to hospice? Or just send him to hospice?” And I looked, and he had a biomarker that indicated that he might have an excellent response to immunotherapy, so we gave him solely immunotherapy and saw him back a few days later. He was still pretty touch and go. We gave him some fluids. A week after that – still, we were kinda touch and go, but he was still with us.
And then a week after that my medical assistant, comes in, and she says, “You know, he looks a little bit better today.” And he was in a wheelchair that day. And then a few weeks after that, he had a walker, and a few weeks after that a cane and about a year after that was asking me about whether or not he could go on a cruise. Again, I still see this gentleman – a couple weeks ago. It’s now almost two years later. And the question now that we have is – should we stop his treatment? And he is restored to complete full health, has had almost no side effects of treatment.
So again, this is not every patient. Some people will be treated and get every side effect and no benefit, but I think I’ve become a lot more reluctant to say that any patient should not at least be offered the opportunity for treatment knowing what the potential side effects are. And there still are considerable and sometimes severe side effects from therapy.
https://powerfulpatients.org/pen/wp-content/uploads/Is-Lung-Cancer-Treatment-Effective-in-Older-Patients_-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 16:09:432020-02-10 09:59:16Is Lung Cancer Treatment Effective in Older Patients?
Sure. Here’s one I hadn’t heard until just now. Surgery causes lung cancer to spread.
Yeah, that’s common in certain states. When I was in Maryland that was a biggie.
So, there’s a myth that the air gets to the tumor, and then it spreads. But that’s certainly not true. It certainly is possible that in a bad surgical procedure that disease can be spread, but I think historically what that was was in the days before we had as accurate of radiographic studies. So, it’s kinda interesting. I always say, “I’m not that old, and I began medical school before there were CT scans.” So, the way you would diagnose something was with a chest x-ray. That was your best chest imaging. And the brain you’d image with something called a pneumoencephalogram, which is – you don’t know what that is. Most people don’t, and they should be thankful for that. But we had no real way of knowing these things. So, what would happen is there would be a surgical exploration. They would say, “Well, it looks very localized.” But then you’d go in, and there was lots of disease all over the place.
And for the most part, that doesn’t happen anymore. Now we have CT/PET scans. We have MRIs. Patients before they go to surgery usually have had – our pulmonary physicians will usually have sampled the nodes in the middle of the chest, the mediastinum. So, it isn’t that there aren’t surprises, but there are far fewer. And certainly, a properly done operation should not spread lung cancer. I would emphasize the properly done operation. It is my strong belief that nobody should have surgery for lung cancer from other than a board certified thoracic surgeon who spends their time thinking about lung cancer, preferably in an institution with a fair volume of this.
We know – it should be no surprise to people, practice makes perfect. People who really focus in an area – people at the NCI-Designated Cancer Centers, comprehensive cancer centers – who do a lot of this have greater expertise.
https://powerfulpatients.org/pen/wp-content/uploads/Does-Surgery-Cause-Lung-Cancer-to-Spread_-The-Facts.-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 16:02:452019-12-12 16:18:44Does Surgery Cause Lung Cancer to Spread? The Facts.
How are you approaching treatment decisions with your patients?
Well, the treatment decisions that we make – that I make are those that are in ways similar to other medical oncologists. It really depends because some of the patients may first go to a surgeon or whatever. However they come into the system, there are a few key factors in this. First is – make your decision based upon, Number 1, which kind of lung cancer. So, there are two major varieties. You have small cell and non-small cell, and they are treated – they are biologically distinct, and they are treated in distinct ways.
And then the next major consideration is the stage of the tumor, which is our way of expressing how advanced that is and deciding on both the therapy as well as conveying a prognosis and evaluating a patient for a clinical trial. And that’s based upon the size and location of the tumor; presence, absence, and location of lymph nodes; and the presence or absence and, these days, the number of metastatic areas of disease.
And then, lastly, and again depending a little bit upon the stage and interacting with all the others is what condition is the patient in? Anybody can get lung cancer, but still the median is in older individuals.
Many of these patients have compromised cardiac and pulmonary status as well as other diseases of aging, hypertension, cardiac disease, etcetera. Those people – one obviously has to tailor one’s treatments to fit those comorbidities. So, that’s sort of how the basic assessment – obviously, some patients show up with metastatic disease. We know that, but we go through a whole process for this.
The staging system that we use is complicated, and it keeps changing. We’re, gosh, up to version eight of this? I started with version three. I’m not quite sure I’ve fully mastered the current one, and the ninth edition is coming soon. And why does it keep changing? Because our knowledge of the disease keeps changing. The database keeps expanding.
We’re able to be more refined. Molecular variables have not yet fully entered into our considerations. Unquestionably, they will. But basically, one could consider lung cancer – despite the four major stages and multiple substages – that you really have three buckets that people will fit into. They have localized disease, which we will predominantly address with a localized therapy – surgery, radiation. And many of those patients, however, particularly those who might have a lymph node that’s positive, will benefit from chemotherapy to prevent recurrence.
We have patients with locally advanced disease. Primarily, those are patients who have lymph nodes located in the middle of the chest as opposed to more localized disease where if there’s a lymph node present it’s more in the lobe of the lung. Those patients with lymph nodes in the middle of the chest or larger tumors are approached with frequently a combination of chemotherapy, radiation, sometimes surgery.
And then we have patients with advanced disease who will be predominantly treated with drug therapies, which nowadays, depending upon the molecular background of the tumor, could be a targeted treatment if they have a specific mutation.
Something we see most frequently, though certainly not exclusively, in patients with scant or no smoking history, they may be approached with immunotherapy or chemotherapy combined with immunotherapy.
And there are many considerations that go into those decisions. And even in advanced stage, there are certainly roles for surgery and radiation depending upon whether there are structural abnormalities, occasionally whether there are relatively few areas or several areas of metastatic disease. And in the localized and locally advanced disease, our goal is cure in those, though we certainly are not there for every patient yet.
And in advanced disease, it’s extension of life, which is now quite considerable compared to untreated disease. And I think in certain situations, particularly those who only have a single area of metastatic disease, curative treatment is a realistic possibility. And even those with more disseminated disease, we’re now beginning to see a substantial fraction of patients who are still alive at five years or more. So, we’re beginning very cautiously to think that perhaps some of those patients may even be cured of their disease, though I’m not quite ready to say that.
https://powerfulpatients.org/pen/wp-content/uploads/Lung-Cancer-Treatment-Decisions_-Which-Path-is-Best-for-You_-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 15:52:012019-12-12 16:34:05Lung Cancer Treatment Decisions: Which Path is Best for You?
So, genetic testing – and in this case the testing of the tumor, not the germline, not the individual – has been very, very crucial. If you go back about 20 years ago, there was a family of drugs called epidermal growth factor receptor inhibitors or EGFR inhibitors.
And the basic science at the time made it look like these would be best combined with chemotherapy in squamous cell carcinoma. And as it turned out, combined with chemotherapy they weren’t very useful. But as single agents, there were these occasional very dramatic results.
So, that came at a time when we were able to evaluate tumor DNA, sequence it with some degree of ease at a reasonable cost. So, there was a discovery of specific mutations, which were targeted by these drugs. So, it was sort of interesting in that it was the clinical observation that led to the discoveries in biology, not really the other way around.
But then that in turn resulted in looking for other mutations, which were found, and then the development of other drugs – in some cases, the repurposing of other drugs for those. And now we have about a half a dozen very validated targets, each one of which in a small slice of the population – between say 1 percent and 5 percent – 10 percent of the lung cancer population – but these – if the patient has within their cancer that particular mutation, these are drugs that are 80 percent-plus effective and frequently can be administered with relatively little toxicity.
And usually they’ll give them benefit for one-plus years or more. So, that’s been an example of progress there.
https://powerfulpatients.org/pen/wp-content/uploads/How-Genetic-Testing-Has-Revolutionized-Lung-Cancer-Treatment-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 15:27:552020-04-07 14:28:37How Genetic Testing Has Revolutionized Lung Cancer Treatment
Let’s start with an overview of lung cancer’s research. Can you tell us a little bit about the field right now?
So, I think the field has been remarkable over the last few years. There’s been more progress, more drugs, more things that have happened in the last five years than probably the prior 50. It’s been an amazing time both for developments in microbiology as well as in immunotherapy of the disease, which is exciting for all concerned.
For patient’s, of course – really a promise of longer, better lives, even cures where we previously did not see any in advanced disease. For the scientists – an amazing amount of new information. And for clinicians and clinical investigators – just almost too many questions for us to answer.
It sounds like the field is really advancing quickly. What do you attribute that to?
Well, you know, I think there are a number of things. Everybody always talks about breakthroughs, but breakthroughs really happen after decades of other work. And what’s happening now is really a result of many, many years of different types of work. There were our colleagues in immunology who built this area of cancer immunology for many years – I have to say with much skepticism from many, myself included.
The advances in molecular biology – our abilities to do things with tumors to determine genetics at a rate and a pace and a cost that was previously unimaginable. All of these things have developed in the last few years but really are a result of the decades of work before that. If you look at immunotherapy – probably one of our biggest areas of progress – the roots of that are a century old. So, nothing’s really new. It’s just now we have the technology and the ability to really use it. And then I would also say that we’ve created the infrastructure that lets us test this – the people who have done the studies, the endpoints for the studies, the expertise in doing clinical trials – that also was there for decades, and we frequently were kind of ridiculed at times.
Oh, you’re just testing this drug against that drug, but the reality is is it was those incremental advances. It was the ability to know the endpoints, to refine the populations, to develop the infrastructure that allowed for all of this to happen.
Dr. Edelman, as a researcher in the field, tell us why you’re hopeful about lung cancer research.
Well, I think that we have gone from trials with very small incremental improvements and frequently a very slow degree of progress where if we had a positive study every two or three years, we were thrilled – to the point where we’ve had an avalanche of positive studies. I don’t think my younger colleagues know what a negative trial looks like anymore. Even our negative trials are pretty impressive. We’ve had studies where an immunotherapy agent was compared with chemotherapy. And it was designed to show that the drug would be better.
And it was just as good, and that was a negative study. That’s the correct interpretation, but still I would point out that that’s quite remarkable because these other drugs had taken us 25-30 years to develop. And now we have another drug with a very different mechanism of action that’s as good potentially. That’s impressive. I think we’ve just had an amazing degree of progress in the last few years. We have far more drugs. We understand far more about the disease – the technology at every point from diagnosis to assessment of response to the ability to evaluate better what we’re not doing well. So, our studies now frequently have biopsies before, during, and after treatment in a way of trying to figure out why is stuff working or not working.
Back in 2006 or so, I proposed a study. We ended up doing it, but it took two or three years because we were requiring a biopsy result – actually, not even a new biopsy but just an archived specimen from the original biopsy to determine eligibility, and there was strong pushback that we would never be able to do that. And now, we routinely are getting biopsies and re-biopsying, and that’s over a brief period of time.
So, we’re getting to get better understanding of the disease, and why stuff works and doesn’t work. And I think that that’s why our progress will accelerate. And I would again emphasize progress only happens – real progress – only through clinical trials. We’ve cured a lot of mice for many decades. A mouse is not a person. You actually have to do the studies patient by patient, and I think we are making substantial progress. We almost have too many things to test right now.
https://powerfulpatients.org/pen/wp-content/uploads/Could-Advances-in-Lung-Cancer-Research-Benefit-You_-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-12-12 15:20:142020-02-10 10:03:14Could Advances in Lung Cancer Research Benefit You?
Dr. Daniel Pollyea, an AML specialist, dispels common myths around the causes and symptoms of AML and shares advice so that you can identify credible resources for information. Download the Program Guide here.
Dr. Daniel A. Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. More about this expert.
I’m Ross Reynolds. Today we’re gonna be debunking some common misconceptions about the causes and symptoms of AML.
And joining me is Dr. Daniel Pollyea. Dr. Pollyea, could you introduce yourself?
Yeah. Hi. Good morning, everyone. I’m Dan Pollyea. I’m an Associate Professor of Medicine here at the University of Colorado, where I am the Clinical Director of Leukemia Service.
I wanna emphasize to you that this program is not a substitute for medical advice, so be sure to consult your healthcare team when it comes to solid information about it. But you will get some background that I think you’re gonna find useful. And you might have some questions as we go along.
Dr. Pollyea, let’s start out with the basics. What are the causes of AML?
Yeah. So, Acute Myeloid Leukemia, it’s a disease, a cancer of the bone marrow.
And it’s the result of an accumulation of mutation and chromosomal abnormalities that affect the DNA of a precursor cell in the bone marrow, otherwise known as a stem cell.
And those abnormalities accumulate until that cell can no longer properly mature, and it also can’t properly die. And so, a cell like that just makes copy after copy after copy of a cell until it crowds out the whole bone marrow with these sorta useless, immature cells.
And the end result of that is the failure of the bone marrow, which causes all of the problems associated with this disease. So, biologically, that’s sort of what happens to make this disease occur.
What are some of the myths that you hear from patients that come in and they say, “Oh, this must’ve caused my AML,” but you have to tell them that’s not so?
Right. So, I mean, this is one of the most frustrating issues for patients and their families after diagnosis. I mean, it’s a rare disease, only about 30,000 cases a year in the United States. And so, trying to associate a rare disease with external or environmental factors is difficult to impossible. So, although there are a variety of exposures that probably contribute to this disease, we have very little understanding of what those exposures typically are or how that all works.
So, there’s a few things that we know pretty well; large doses of radiation, either associated with like industrial accidents like the Chernobyl disaster, or some of the radiation therapies that patients receive for other types of cancer. Other types of chemotherapy that are used to cure other cancers can contribute to this disease in later years.
We know that there are certain precursor conditions that can evolve to AML, so a person with myelodysplastic syndrome, for instance, has a fairly high chance of someday evolving to develop Acute Myeloid Leukemia. But beyond these sort of a few associations, there isn’t a whole lot that’s known or proven.
Now there is radiation associated with X-rays, and some people think that X-rays can cause AML. Is that true?
So, I mean, I think a priori no because millions of people get X-rays every day, and only 30,000 people a year get AML. So, clearly it’s not a simple association between getting an X-ray and developing AML. But I think that there is an unknown interaction between environmental exposures and a person’s individual genetic makeup that makes a person more or less susceptible to developing something like AML with respect to exposure to the environment or X-rays and things.
So, while you cannot say that getting an X-ray will lead to AML, certainly there are some people who are more sensitive to the damage that’s done by something like an X-ray. And so, the best course of action is to be cautious and judicious about your exposure to these things, but not to not get these things when they are medically necessary.
So, that’s the challenging balance.
Here’s something else we’ve heard, that weed killers can be a risk factor for AML. Is that true?
I mean, I think there’s a lot coming out now about weed killers and their association with other types of cancers. Again, I go back to the limitation we have in that in only 30,000 people a year in the United States get AML. Millions of people are exposed to weed killers.
We’re statistically never going to be able to make a clear association. I think that there are certainly some risks for some people. Whether you’re that person who’s more susceptible to developing leukemia or any other cancer because of exposure to a weed killer is impossible to know.
So, like all of these things, I think the advice we have is you have to live your life. You have to do your best to sort of avoid things that you can avoid that you think would be… Or that may cause problems. But not to let those things prevent you from living a normal life.
I know that’s not a satisfying answer, but at the moment that’s the best answer we have.
Is formaldehyde exposure another risk factor for AML?
Yeah. We think that it is, and kind of along the lines of benzene. But, again, we think that those studies that have shown those types of association show it in very high amounts, amounts that most people in this country would not be exposed to. But I do think, or we do think that there is something to that, to formaldehyde somehow contributing to this.
What’s the difference between a risk factor for AML and a cause of AML?
Yeah. So, I think risk factors by definition are things that may contribute to AML. And a risk factor for AML by that definition could be walking down the street and having some exposure to radiation from the sun. A cause of AML is something that is a much more solid sort of well-understood factor.
Like I said before, having myelodysplastic syndrome, there is a high chance that that can evolve to Acute Myeloid Leukemia. And if that happens then the MDS, the myelodysplastic syndrome, could be considered or would be considered the cause of your AML. So, very, very different in terms of the amount of evidence that goes into making those determinations
Is there a genetic component to this? Can this run in a family?
Yeah. So, this is a disease of the genome.
So, I mean, in a lot of respects it is a genetic disease. But the question is very different when you ask is this an inherited genetic disease? Is this disease due to a gene that I inherited from a parent or could pass along to a child?
For many, many years, the answer from the medical community was, “No.” This was not considered to be a disease that clustered in families or that could be inherited. We now know that that’s not necessarily the case. There are some very rare cases where this does seem to travel in families or cluster in families. And we’re now beginning to understand who those people are and what those genes are.
But the vast majority of people with this disease did not inherit a gene to contribute to it and cannot pass this along to a child. This is a random, spontaneous event that occurred within one person’s own body and is not traveling within family. So, we’re learning more and more about this, but really, the vast majority of this is not an inherited genetic condition.
You’ve mentioned gene mutations. What mutates a gene? What causes that to happen that could lead down the line to AML?
Yeah. Yeah. That’s a great question. Most of the time we do not know the answer to that. These gene mutations occur spontaneously, randomly, and we don’t understand why they happen when they do happen.
And I know that’s, again, not a satisfying answer. It’s very frustrating, particularly patients come in, and, “I’ve lived a healthy lifestyle. I’ve done everything right. I exercise. I eat right. How could this have happened?”
These are things that for the most part are out of the control of a person. These aren’t impacted by your diet or your activity levels, what you eat or don’t eat, what you do or don’t do. That’s a real frustration. In the end, in almost all cases we don’t know or understand why these gene mutations or these, I call them mistakes in the body, occur when they occur. We don’t understand them.
And, Dr. Pollyea, someone asked if benzene can be a risk factor for AML.
Yeah. So, benzene is one of the sort of rare environmental exposure associations that we do have clear associations with AML.
But the level of benzene that a person would need to be exposed to is really something that hasn’t been seen in this country in a very long time.
We’d be talking about like an industrial accident type exposure in almost all cases, so being exposed to a cleaning solution or some other fairly minor exposure to benzene, we don’t think is enough, in most cases, to prompt this disease. But benzene in very high doses, like an industrial accident, yes, that is something that we understand can certainly contribute or cause AML.
Autoimmune diseases, such as arthritis, can they increase the risk of AML?
Oh, boy. That is a really interesting one. So, there are papers in the literature that do support those associations. And I know in my own practice I certainly see that trend. So, I do think that there is something there. There is a proven association between autoimmune conditions and myelodysplastic syndrome, which I said before can be a clear precursor condition to AML. So, certainly, that is an association that is a possibility.
It can be a little difficult to tease out whether it’s those diseases that are associated with ultimately developing AML, or the treatments that people get for some of those autoimmune diseases. Those treatments can modulate the immune system in certain ways that may, in fact, contribute or drive the disease. So, that’s a difficult thing to tease out.
But in general terms, yes, I think there are some associations. Now not by a long shot everyone with an autoimmune disease gets AML. It’s a teeny, tiny fraction. But I think there is an association there.
How easy is it to diagnose AML?
Well, I mean, I think there’s very clear diagnostic criteria for AML. But I guess that doesn’t really answer the question. And we certainly have patients who come to us after many months of frustration without a clear diagnosis.
So, those scenarios can play out. Many times AML’s a very dramatic presentation, so people get very, very sick very, very quickly with extraordinarily high white blood cell counts and suppression of all the other blood counts that come from the bone marrow like red blood cells and platelets.
In those cases it’s pretty clear that there is a type of acute leukemia going on. There can be some difficulty distinguishing Acute Myeloid from Acute Lymphoblastic Leukemia; those are sort of like cousins, but very different and treated differently. So, it kinda runs the gamut. I mean, it can be pretty clear, but it’s sometimes missed, so yeah.
This is a great lead-in to my next question, which is about the symptoms of AML. What should be the warning signs that this might be something you need to get looked at?
Right. So, at presentation, the main symptoms are reflective of the fact that the bone marrow, the organ that makes all the cells of the blood, has failed.
So, that can cause severe anemia. Signs of anemia: a white sort of appearance, feeling dizzy or lightheaded when standing, short of breath, weak, tired, fatigue. Those are all pretty clear presenting symptoms for AML. Because the bone marrow also is responsible for making platelets that clot the blood, some people will present with a bleeding complication, or a very subtle rash made up of these particular red dots. We call that a petechial rash. And that rash can come on when the platelet count gets very low.
Sometimes a person will present with an infection or infections that don’t go away or don’t clear because of decrease in white blood cells, the infection-fighting cells of the bone marrow. Those are made in the bone marrow and can fail in the setting of this disease. So, those are the most common symptoms at presentation, symptoms that are reflective of bone marrow failure.
You mentioned that sometimes the presentation could be very dramatic, and it sounds like the symptoms are very severe, very quickly. Is that always the case? Is that often the case?
That is the case in, I would say, a minority of times. That’s usually the case. It’s more often seen in younger patients with AML. Typically, older patients with AML have a more smoldering course and a much less dramatic presentation, although this sort of very dramatic and dangerous presentation can happen in older patients, but it’s probably something like a third of the time that those very dramatic and medical emergency presentations occur.
How important is early diagnosis?
Well, I mean, it’s crucial. I mean, in particular in those cases where it’s a very dramatic and proliferative diagnosis, or presentation. A quick diagnosis and recognition of this condition is very important because the sooner a person starts effective treatment the better the ultimate outcome is.
I would say in general terms that applies to all AML patients, but certainly there’s some degrees of variation. So, there’s some AML patients that when I hear about their case on the phone from a referring doctor, it’s appropriate to see them next week in the clinic.
So, it’s not always a medical emergency, but we would never, even in those next-week-in-the-clinic patients, this isn’t something that can wait for weeks or certainly months. This is something that needs to be addressed fairly quickly.
What are the best ways to manage those symptoms?
Right. So, I mean, at presentation, all those symptoms, the best way to manage those are to start treatment as quickly as possible. So, impacting the underlying cause of this disease is the most important and critical factor to getting a person feeling better because all of these problems stem from the disease in the bone marrow, and so everything else that you do to sort of help a person’s symptoms are Band-Aids when you’re not talking about getting to the root cause.
So, that’s at presentation. Now once we start treatment, there are many potential side effects to any number of treatments. And it all is dependent on what treatment you’re getting and other things about you that will make this a significant problem in some cases. And in that setting, we do have ways that we can aggressively manage a person’s side effects.
Can you manage all of the symptoms? Or can people still be experiencing symptoms even after they’re in treatment?
Absolutely. So, a person with this disease, depending on how long they’ve had it and some of the features, may not be feeling back to their baseline self for potentially weeks or months after treatment starts in the best-case scenario. So, that can be very frustrating, but a person needs to sort of be able to continue to have a good outlook and stay positive.
Because we are able in many cases to make a big impact on this disease and return a person to their pre-disease quality of life.
What are some of the myths that you hear, Dr. Pollyea, about the treatment? Some things that people come in to you saying they think that it helps, but there’s no science to back that up?
So, myths about treatment, so many people have a lot of preconceived notions about the intensity of a therapy that they’re going to be asked to withstand. And although sometimes we do treat this disease very intensively, that’s not always the case, and now we have some very effective lower-intensity regimens that can be used in a variety of different scenarios.
There are a lot of people who have a lot of preconceived notions about a stem-cell transplant or a bone-marrow transplant and whether or not they would be eligible for this based on maybe what they’ve heard from friends or family, or what they’ve seen in the internet.
And those are often incorrect. And so, keeping an open mind about treatment options, and discussing those in detail with your doctor are really, really important.
You mentioned sometimes it presents in young people, sometimes in older people. What’s sort of typical?
This is a disease of predominantly older patients, so the median age of presentation is 68. So, that means that over half of the patients are over 68 years old at diagnosis. So, while this does happen, can happen in younger patients, that’s really an unusual situation. This disease is, like I said, it is predominantly a disease of older patients.
There are some patients who I understand think that supplements can deal with the symptoms of AML. Is that accurate?
You know, I mean, I think the supplement question is always a challenge. A lot of these supplements, or most of these supplements have never been tested with the rigor of treatments that we’re accustomed to in the medical establishment.
That being said, I won’t deny that some of the supplements can help patients based on what patients’ experiences are and what they tell me. I think what’s really important is just be very open and honest with your doctor about the supplements that you’re taking or want to take to ensure that there are no sort of unanticipated interactions with treatments.
Because I think most doctors are very open to having their patients care for themselves in the ways that they’ve become accustomed to, and they know their bodies very well, and we’re very open to that. But there are sometimes that a drug or a supplement might have a bad interaction with the treatment.
And so, a good example in my practice is antioxidants. So, there’s a lot of literature, a lot of interest in antioxidants as cancer-prevention treatment.
And a lot of that is not well-established, but still I don’t see much harm. But when it comes time to treating a cancer, that’s a very different situation. When we give a patient treatment to try to kill the cancer cells, many times we’re trying to provoke oxidation. That’s part of how these drugs and these treatments work.
So, if you’re taking those treatments, but also at the same time taking antioxidants, there’s the potential you could sort of be cutting your therapy off at the knees, fighting it with one hand behind your back. So, for the period of time when my patients are getting an active treatment, I ask that they don’t take it antioxidant.
And they can resume that in the future in the hopes of preventing another cancer. But the time to prevent with an antioxidant isn’t appropriate when you’re dealing with an active cancer. So, that’s just one example.
Fatigue could be a symptom of AML, but there are a lot of causes of fatigue.
How do you differentiate between something that really could be AML and something that isn’t?
Yeah. That’s a challenge because I think these are, as I said, older patients. And older patients have a lot of other medical problems. And older people get fatigued, just that’s unfortunately part of the normal aging process. So, we would usually make an assumption that a person’s fatigue and diagnosis is due to the leukemia, the anemia as a result of the leukemia.
But as we successfully treat a patient if they are responding based on their numbers and other objective criteria, but the fatigue is not improving then I think that’s where we would start to look at other contributing factors, and there can be many, so having an open mind at that point is important.
But at the beginning, this is such a monster of a disease, it’s so overwhelming, I think the focus is usually on assumption that the fatigue is due to the disease or to a treatment associated with this disease.
This question: is loss of appetite a symptom of AML?
Yeah. I definitely see that, hear that, so sometimes people come in and they say that. Sometimes it may not be a loss of appetite, but an extreme weight loss, so a lot of different types of cancer, including AML, can cause that, just basically unintentional weight loss.
A person’s not trying to lose weight. They’re eating what they think is their normal amount and they’re losing tremendous amounts of weight. So, those are both potential presenting symptoms with AML. And loss of appetite, unfortunately, can be associated with some of the treatments for this disease. And taste changes, things not tasting good, can all contribute to that as well, so those are all challenges that our patients face.
How important is to get a second opinion? I mean, are all doctors like you pretty much on the same page when it comes to symptoms and treatment?
So, this is a challenge. So, the answer to the second question first is unfortunately, no. A lot of this hasn’t quite been standardized. And some doctors, oncologists, cancer doctors, they’ll predominantly be treating the things that are common: colon cancer, breast cancer, prostate cancer. And they will probably only have a few cases of acute leukemia a year.
And so, their approach to this is going to be different than somebody who spends all day seeing patients with AML and thinking about AML.
So, a second opinion is a very nice thing to be able to do. The problem with this disease is that most times it doesn’t afford that opportunity. So, with other conditions you have some time to go out, read about it, talk to some different doctors, get a good plan together.
With AML, often that’s not a possibility. A person is so urgently sick that you have to sorta deal with the resources where you are. The best recommendation I have there, if you do find yourself in a situation where there’s not a lot of expertise is to ask your doctor to just call somebody in the region or email somebody in the region who may have that expertise.
And most doctors all over the country have that sort of resource or partner that they will go to and talk the case through with them, and maybe a transfer to one of those high-volume centers is appropriate.
And maybe that’s not a possibility or appropriate, but maybe you would benefit from just talking… Maybe your doctor would benefit from talking this through. But in cases where it’s not such a dramatic presentation, then yeah, for sure, I think a second opinion can be appropriate. But this isn’t something that can be sort of drawn out for long period of time.
You know, when you find out something like this, your tendency might be to jump on the web and start searching for AML. How do you vet those sources that you look at? How do you figure out that their – what would be a sign that they’re bogus sources?
Yeah. I mean, I think this field is so rapidly changing and the treatment that we have, that I would, for the most part, assume that what you’re finding on the web is not relevant and is not an up-to-date resource. So, the resources that I listed, the NCCN, UpToDate, the Leukemia & Lymphoma Society, I should mention.
A very important resource that has up-to-date information, and they have even phone numbers for patients and their families to call to get connected with the proper people in a particular city, so that is a really important resource. But I’d be really, really cautious about what you find on the internet because things are changing so fast in this field. There’s a lot of outdated and misinformation on the internet.
Well, then there’s outright scams. One of the things you mentioned before we went on is be cautious if someone’s asking you to put money upfront, or if it’s a nonmedical facility. What are some things that people should watch out for?
Yeah. So, one of the things that is so important in our area is clinical trials and participating in clinical trials. Patients who opt to do this and receive experimental therapies can sometimes get the treatment of the future, get a drug that’s not currently available through the FDA, but may have a lot of promise.
And this is the way that we fight this disease. We’ve recently had an onslaught of approvals for AML and that’s because the patients being willing to participate in sanctioned clinical trials. So, participating in a sanctioned clinical trial is crucial, and it’s always a recommendation of all leukemia doctors.
When you participate in a conventional clinical trial, you’re asked to sign a consent form that explains what you’re doing and why. There is a confirmation that this has been vetted by an institution’s regulatory board that is prioritizing the safety and well-being of you, the patient. This has been approved by the FDA as a clinical trial. Nobody would ever ask you to pay money. That’s not ethical to participate in a clinical trial. Insurance covers whatever standard of care. And the clinical trial covers anything that isn’t.
So, if you find yourself in a situation where you’re not being asked to sign a consent form, where a clinical trial has not been reviewed by a regulatory board, where your doctor is not a leukemia specialist, where the FDA has not sanctioned the treatment, all of those are alarm signs.
Because there are people out there that are preying on patients in a desperate situation, a very difficult time in their life, and giving them sort of false hope and leading them down paths that are not legitimate.
One easy thing to do to sorta check to see if a clinical trial is legitimate is to go onto clinicaltrials.gov.
This is a resource set up by our national healthcare system that now feeds in every legitimate clinical trial from all over the world, needs to be registered on clinicaltrials.gov. So, if you can’t find your clinical trial on clinicaltrials.gov, I would have a lot skepticism and caution about that.
Like what advice do you have for people when they’re first diagnosed? What are the first things they should try to do?
Yeah. I mean, that reaction is totally normal and natural. I mean, many times these people are perfectly healthy or have been perfectly healthy, and this news is a complete shock.
And so, it is normal and appropriate to have some period of grieving for the healthy life that you are losing. But I would also, while giving yourself that time to grieve, first, draw on your support system, your family, your friends. Allow them to help you. Accept that assistance that they have. And to be optimistic because we are getting so much better at treating this disease.
I had mentioned before, there has been an onslaught of approvals for drugs in this area the likes of which hasn’t been seen in decades. We have new tools and weapons in our arsenal that we couldn’t have dreamed of even a few years ago.
We in our community are very excited and hopeful about the future and we hope that that will translate ultimately to patients, but being depressed or being down, being scared, all of that is normal.
All of that is expected. Anyone would feel like that. Allowing yourself to have those feelings and emotions is important, as long as it doesn’t get in the way of doing what you need to do to fight this disease.
It sounds like you’re hopeful about new treatments for the disease. How about a cure? What’s the science? What’s the medical science say about that? Are we getting any closer to that?
We are getting closer to curing this in more cases. So, like I mentioned before, as bad as this is, we can already cure some subsets of patients. There’s one type of Acute Myeloid Leukemia called Acute Promyelocytic Leukemia, APL. It’s an uncommon form of AML, less than 10 percent.
But we can cure close to 99 percent of people with APL. And APL, 15 years ago, was universally the worst form of acute leukemia to get. So, that dramatic 180 that we’ve seen in APL, we are hoping to translate into other forms of AML.
Some other forms of AML have cure rates as high as 50 percent, 60 percent, 70 percent in the right setting. Sometimes we can cure patients with a stem cell transplant fairly reliably. So, we are very, very hopeful about our ability to continue to make progress and cure more and more and more of these patients. That’s the future that we see.
Dr. Pollyea, thank you so much. And thank you so much for ending on such a positive note. We really appreciate it. And thank you for joining us for this program today.
To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Ross Reynolds. Thanks for joining us.
https://powerfulpatients.org/pen/wp-content/uploads/Pollyea-1.png600600Kara Rayburnhttps://www.powerfulpatients.org/pen/wp-content/uploads/New-Logo-300x126.pngKara Rayburn2019-06-05 15:38:122020-02-05 16:27:13Fact or Fiction? AML Causes & Symptoms
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