What Are Potential Impacts of Artificial Intelligence on AML Patient Care?

What Are Potential Impacts of Artificial Intelligence on AML Patient Care? from Patient Empowerment Network on Vimeo.

How might acute myeloid leukemia (AML) patient care be impacted by artificial intelligence? Expert Dr. Andrew Hantel from Dana-Farber Cancer Institute and Harvard Medical School shares his perspective on potential risks and benefits of the impact of AI on AML patient care.

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Transcript: 

Lisa Hatfield:

Dr. Hantel, can you elaborate on the significance of oncologists believing that AI-based clinical decision models need to be explainable? And how might this impact AML patient care and decision-making processes?

Dr. Andrew Hantel:

Sure. So I think just taking a step back and saying you know what is AI, and what does explainability of AI even mean? So AI or artificial intelligence is essentially computer algorithms that learn to some extent like us, but in other ways differently, kind of how to process information and make decisions based on that information or make recommendations, at least.

And to some extent, like you or I, we can’t really explain “Why did I decide to have Cheerios this morning versus having like whole wheat toast or something?” It’s kind of difficult for me to say, “Oh, I just felt like I wanted to do that instead of that.” To some extent, AI also does that. It can kind of arrive at a decision after digesting a lot of different data over its lifetime to say that it prefers Cheerios versus whole wheat toast.

But it can’t necessarily tell you why it wanted one versus the other. And in medical decisions, to some extent, the same things can happen. It can’t really adequately explain to some extent why it might recommend one treatment versus another. And we like to think that in medicine, we’re making evidence-based recommendations that we choose treatment one or treatment two over treatment three, because the evidence for one and two is better for the person in front of us.

And AI can also kind of explain things some ways to that extent, but in other ways it might not know all of the other characteristics of the person that aren’t in that computer that make us think treatment one or two is better than three. And so our ability to actuallyd say, “Is the AI making this decision appropriately and able to explain why it came to decision one and two?”

If it can’t do that, we can’t actually understand whether or not it’s gone wrong and whether or not we should trust what it’s recommending. And so for that, we kind of have to create artificial intelligence models that are explainable by saying, “I’m telling you, you should choose this option versus that option because of reasons A, B, and C as they apply to this patient who is being taken care of.” And the hope is that there are ways computer scientists are using to try and get AI towards that.

But we really need to make sure that we create an AI that’s trustworthy in order for us to make you know AML patient care decisions that do better for our patients, because we know that AI is powerful, and it can bring in a lot of different data sources that are difficult for any human to make in any kind of scenario. But to be able to do that in a way that doesn’t put patients at risk and that really improves their care and improves our ability to maintain and optimize people’s health is essential. And so while AI is not kind of right now being used to make decisions in AML patient care, it’s going to be tested probably in the near future to help out with that in clinical trials and controlled settings.

And so you as a patient or somebody who is very interested in the power of AI, I would say once we start to hear about those things, it might be something that you’re interested in participating in a trial, or you’re interested in kind of learning more about that. We could come back and talk about that more. For the moment though, I think it’s just more of a risk that we’re trying to avoid of making AI that’s not explainable and potentially harms patients rather than helps them.

Lisa Hatfield:

Okay, thank you. One of the things I know in some cancer research is they are using artificial intelligence and machine learning models to help predict outcomes based on certain therapies. And I wonder if you have any comments on, because the data used is historical and real time coming in all the time, but we know there are inherent biases based on disparities in healthcare anyway from underrepresented communities. Do you think that those biases can be overcome in future models that are used to predict outcomes to treatment for different types of cancers?

Dr. Andrew Hantel:

Yes. So I think there’s a number of different biases that can come into artificial intelligence models. And it’s the same, a lot of the same biases that we have in our current clinical trials, and that historically marginalized groups have not been well-represented, either in participating in trials or in their data that’s input into these AI models. And for kind of the same reason, we don’t really know how generalizable the data that we have from the trials or from the AI really apply to those populations.

We assume because they have a lot of the other same characteristics as the people who are in the trials or kind of in these models that we can apply those data to them. But I think the push is to use both data sets and to encourage participation in trials for those communities, such that we know that these drugs and that AI are safe and effective for them.

And so there are both efforts to do that in leukemia and cancer broadly, and across healthcare even more broadly. And that can be either by working together with kind of multinational consortia of physicians and researchers to kind of pool data that includes patient populations from around the world. And the same thing is being done for trials as well as to kind of help make sure that the people who are underserved also kind of within our own communities are included in both of these processes.

Lisa Hatfield:

If a patient were to come on to you and said, “Dr. Hantel, I looked up on ChatGPT, what is the best treatment for me given these mutations or this characteristic of my disease?” What might you say to them? Would you involve that in your decision-making? Would you discuss that with them a little bit more? How would you handle that?

Dr. Andrew Hantel:

I think I would just generally be curious about you know what the actual transcript of the conversation was like. I think right now one of the major concerns for a lot of AI is that it can hallucinate things. And so there are some famous examples of lawyers putting in you know kind of briefs that they wanted to file and the AI coming up with like court cases that never existed to justify things. And so the last thing that we want is in medical decisions for people to rely on kind of made-up facts to make treatment choices.

And so, I’d be interested in kind of its medical decision-making process and kind of the data that it was able to rely on to make the decision. More from the standpoint of curiosity and education for myself to understand how patients are interacting with these things, as well as to make sure that the patient was also understanding kind of the information that was being put out and wasn’t having any misconceptions.

I think that the potential for these AI to help patients is vast in terms of their ability to understand a lot of the medical jargon and a lot of the information that’s coming at patients through portals and everything else, that could be very scary. But I also want to make sure that we’re not kind of overloading patients with what we think is an answer, but actually can come with a lot of falsehoods and harm.

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AML Research: What’s New in Treatment?

 AML expert, Dr. Jessica Altman, discusses the future of AML research, and new learnings that continue to improve current treatment approaches.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about Dr. Altman here.

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Transcript:

Patricia:            

Are there any new treatments on the horizon that you can talk about, Dr. Altman?

Dr. Altman: 

Absolutely. So, I love to talk about new therapies in AML. Until the last couple of years – it had been 40 years since we approved a sustained treatment in the marketplace in AML. We had been treating the disease the same. And over the last couple of years there have been a growth of therapies. We’re now trying to sort out exactly when we’re using one over another. We also have clinical trials where we’re combining novel therapies for adults with either newly diagnosed disease or relapsed and refractory disease. 

We are in an era of looking out at antibody therapy in AML – that’s one of the new waves of treatment. We are still exploring targeting therapies in the sense of inhibition of FLT3, IDH, and other mutations. So, it’s an era where there’s lots of excitement, and I’m hopeful for our patients.

Patricia:     

Yeah. Tell me what makes you most hopeful about the future of research in this area, and treatment?

Dr. Altman: 

So, I think that’s a great question. I think the fact that we now – the deeper the understanding we have of the biology of the AML, why AML happens, what mutations drive the disease, and then how to target those mutations with individual therapies is what excites me the most. So, our basic science research has exploded, and that occurs at a very quick pace, and that’s allowing us to develop therapies at a much faster rate than I would have anticipated before.

Patricia:

What a wonderful way to end our chat. Thank you so much, Dr. Altman, for taking the time to join us today.

Dr. Altman: 

It’s a pleasure to be here. Thank you so much.

Misconceptions in Clinical Trials: What’s Fact and What’s Fiction?

AML expert, Dr. Jessica Altman, addresses common misconceptions patients have about clinical trials regarding treatments, regulations, and standards of care. Want to learn more? Download the Program Resource Guide here.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about Dr. Altman here.

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Transcript:

Patricia:            

What about clinical trials? What common misconceptions do patients have about enrolling in trials?

Dr. Altman: 

So, I think the misconceptions regarding clinical trials can be very masked. And I think it really depends on the intent of a clinical trial and the phase of the clinical trial. I think that a well-designed clinical trial is almost always the right choice for a patient with acute leukemia at any stage in their therapy. 

That is a bias as a clinical trialist. I think it’s the right bias, but it is still my bias. I think patients frequently worry that they’re being treated as a guinea pig, or they’re not getting an appropriate treatment. What I can tell you is the clinical trials that we and my colleagues across the country and across the world participate in are clinical trials where the patients are getting at least what we consider a standard of care for that phase of their disease, and they may be getting something in addition to that or something that is slightly different, but expected to have a similar response rate. 

We have this phrase in clinical trials, something called equipoise, that if there’s a randomization between options that we need to feel, as the practitioner and as the clinical trialist, that each option is at least as good as the other.  

Patricia:

That kind of goes back to the vetting of treatments before they go to a clinical trial. Tell me a little bit about history. How can we make patients feel more comfortable?

Dr. Altman: 

I want to make sure that I understand the question.

Patricia:

So, how thoroughly are treatments vetted before they go to a clinical trial?

Dr. Altman: 

Great. So, the way that agents get into early phase clinical trials and then later phase studies are these are compounds that have been studied in the laboratory, then studied in small animals, then larger animals. And then, frequently, a drug is started in a patient with relapsed and refractory Acute Myeloid Leukemia and found to be safe – that’s what we call a Phase I study. 

Once we know the right dose and the associated side effects from an early phase clinical trial, later phase studies – i.e. Phase II, where the goal is to determine the efficacy and response rate is conducted. And then, if that appears and looks like it’s promising, a larger, randomized, three-phase study is frequently conducted, where we compare a standard of care to the new approach. 

Patricia:

So, patients should be comfortable that the clinical trial that they’re going through has been thoroughly vetted, has gone through multiple stages before human trials occur?

Dr. Altman: 

That is accurate in terms of compounds get through animal studies, and then depending on the way that the trial is being connected, will then be studied in patients either with relapsed or refractory disease or very high-risk disease. But it’s also very important to mention that these pharmaceutical companies and physicians are not making these decisions alone. 

The clinical trials are all reviewed by scientific review committees through the cancer centers, which are other investigators making sure that everything appears appropriate. In addition, there are institutional review boards at every university whose goal it is to keep patients and research subjects in well-done clinical trials safe. That is their primary goal. And the IRBs – institutional review boards – are very involved with making sure that clinical trials are appropriate and that the conduct of clinical trials is appropriate.

Addressing Common Myths About AML Treatment

AML expert, Dr. Jessica Altman, discusses common myths surrounding available AML treatment options, stem cell transplant and how leukemias are classified.

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Transcript:

Patricia:            

Dr. Altman, let’s talk about some AML treatment myths floating around. I’ll throw some stuff out there, you let me know if you’ve heard this. “Leukemia is one disease.”

Dr. Altman: 

So, I have heard that. Leukemia is actually a number of different diseases, and it’s very heterogenous. There are acute and chronic leukemias. The acute versus chronic really depends on a couple of factors. The biologic factor is the presence or absence of 20% loss or more in the bone marrow, but that also coincides with how patients present clinically. Acute leukemias tend to present more acutely, more rapidly. And chronic leukemias tend to be a bit more indirect. And the treatments are very different for those entities. 

There are also myeloid or lymphoid leukemias, so there’s Chronic Myeloid Leukemia and Acute Myeloid Leukemia and Chronic Lymphocytic Leukemia and Acute Lymphoblastic Leukemia. So, those are the four major categories. We’re talking about Acute Myeloid Leukemia today. Within Acute Myeloid Leukemia, there are multiple different types of Acute Myeloid Leukemia that are really now best categorized by history – patient history – and the molecular and cytogenetic abnormalities of the disease. 

Patricia:

Now, we’ve already learned about a bunch of them. So, “There are limited treatment options” is definitely a myth. Correct, Dr. Altman?

Dr. Altman: 

So, we have had a major growth of the number of treatment options available for Acute Myeloid Leukemia really in the last couple of years. It’s been a very exciting time for practitioners and for our patients that we have now a number of new therapies. So, there is not just one treatment available. In fact, the conversation regarding treatment options becomes quite extensive with patients and their families, because there are choices. And that’s why consideration of goals in the intent of treatment becomes even more important. 

Patricia:

Here’s another one: “Stem cell transplant – the only chance for cure.”

  Stem Cell Transplant, also called a bone marrow transplant, is a procedure in which healthy blood stem cells are used to replace damaged or diseased bone marrow. This procedure can be used to treat certain types of blood cancers.

Dr. Altman: 

Okay. So, that is also a myth. There are certain types of Acute Myeloid Leukemia where stem cell transplant is the most appropriate treatment once the disease is in remission if the goal of the patient is of curative intent. Stem cell transplant is not appropriate for every individual, and for some types of Acute Myeloid Leukemia, stem cell transplant is not considered. 

Patricia:

What kinds of things do you think about when you’re considering a stem cell transplant with a patient? 

Dr. Altman: 

So, again, I go back to patient goals and understanding their goals of treatment. A stem cell transplant is among the most medically intensive procedures that we have. It is also not just a treatment that occurs over a short time. While the actual transplant is a relatively limited hospitalization and the administration and infusion of stem cells and preparative chemotherapy, it is something that can continue to have side effects and alterations in life quality that can persist for months to years afterwards. 

So, that’s one aspect of things that we talk about regarding stem cell transplant. And really understanding what the benefit of transplant is in terms of a survival advantage, versus what the risk and the cost in terms of toxicities are. And that’s the basis of a lot of the conversations we have.

Patricia:

Sure. Here’s one more: “AML patients require immediate treatment.”

Dr. Altman: 

Sometimes AML patients require immediate treatment, and sometimes they don’t. And that depends on the biology of the disease. How high is the white blood count when the patient comes in? What are the best of the blood counts? Is the patient having immediate life-threatening complications of their acute leukemia? 

And there’s some forms of acute leukemia that require immediate therapy to prevent complications, and there’s some forms of acute leukemia who present an extreme distress from their disease, but there are many patients who present with acute leukemia, and we have time to get all of the ancillary studies back – the studies of genetics and the molecular studies1 – to help further refine the conversation, and further design an appropriate treatment strategy. 

Patricia:

What else? What do you hear from your patients that you feel is maybe a misconception or something they’re not quite understanding about the AML?

Dr. Altman: 

So, I think one of the biggest things that I would like to mention is that response rate and cure are not the same. So, it is possible for one to be treated for Acute Myeloid Leukemia and the disease to enter remission, and yet still not be cured of their disease. 

Acute Myeloid Leukemia is a disease that frequently requires additional cycles of treatment or a stem cell transplant after the initial induction therapy to be able to have the best chance for a long-term cure. So, response and cure are not the same thing.

Valerie share’s her story for AML Awareness Month

This video was originally published by CancerCare on June 17, 2016, here.

 

AML Genetic Testing: Could It Lead to a Targeted Treatment for You?

AML Genetic Testing: Could It Lead to a Targeted Treatment for You? from Patient Empowerment Network on Vimeo

AML expert, Dr. Pinkal Desai, outlines the reasoning behind the necessity of cytogenetics and molecular testing when managing an AML diagnosis. Want to Learn More? Download Your AML Navigator Resource Guide, here.

Dr. Pinkal Desai is an Assistant Professor of Medicine at Weill Cornell Medical College and Assistant Attending Physician at the New York-Presbyterian Hospital. More about this expert here.

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Transcript:

Dr. Pinkal Desai:         

So for patients who are undergoing molecular testing or any diagnosis of AML, both cytogenetics and molecular profiling are important, so they do not supersede each other. This is the conglomerate information that we need from the diagnosis to make important medical decisions. Usually the diagnosis would include: looking at the cells under the microscope by the pathologist; flow cytometry, which is a way to identify the subtype of leukemia; chromosomes or karyotypic analysis, which is to look at the individual chromosomes and whether they are abnormal in these leukemia cells; and the last one would be the molecular mutations, which would be single-gene profiling of the leukemia cells.

All of these are important, and it’s not that one can be omitted. They’re all part and parcel of the diagnosis of AML, and all of them should be done.  

So my advice to patients whenever this topic comes up of molecular mutations is always an unequivocal – there should be no question that this should not be done. The advice is plain and simple. This has to be done at diagnosis and, in certain cases, at relapse as well in order to figure out the best treatment possible. If they’re at a site or a clinic where this molecular testing is not available, then they should seek a second opinion to a site that would do this testing because in this day and age of leukemia, there is no treatment and diagnosis that can be done without all of these components in place.

In the old days, we didn’t have a lot of treatment in AML. It was either chemotherapy or hypomethylating agents, and that’s it. But now we have several drugs, five or six of them, that were just approved in the past two years specifically for leukemia and targeting some of these mutations. We have Midostaurin, Gilteritinib, Ivosidenib, Enasidenib, and I don’t want to go on and on about these drugs, but the most important thing is that in this day and age where you have so many drugs, how to incorporate these drugs into the management for patients, both upfront and in the relapse setting, it’s extremely relevant to do this testing, and this is highly encouraged and should be done as part of the diagnosis and treatment.

What’s Next in AML Treatment and Research?

What’s Next in AML Treatment and Research? from Patient Empowerment Network on Vimeo.

Dr. Pinkal Desai, an AML specialist, discusses research in-progress on MRD testing and pre-disease mutations in leukemia.

Dr. Pinkal Desai is an Assistant Professor of Medicine at Weill Cornell Medical College and Assistant Attending Physician at the New York-Presbyterian Hospital. More about this expert here.

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Transcript:

Dr. Pinkal Desai:         

So we at Weill Cornell are a big leukemia center, and we are leading a lot of the clinical trials in AML, both in the upfront and the relapse setting. There are several research initiatives that we are highly interested in. One of them is how to incorporate some of these targeted treatments, both in the upfront and in the relapse setting.

The most important one that we’re actively working on is to monitor these patients, so MRD testing, or minimal residual testing, is extremely relevant in order to figure out whether the treatments are working in the right fashion, and would you change treatment or would it impact the patient’s overall survival if some of these mutations persist or not.

And we are really interested in monitoring these patients and these mutations to figure out a plan which is targeted not only for the mutation but also for the specific patient, and that is one of the things that we are very interested in and doing at Cornell.

We’re also looking at pre-disease mutations. There are several mutations – this is personally my research interest as well – there are certain people who are at risk of developing leukemia; for example, people who are undergoing chemotherapy for other cancers, and the presence of some of these mutations before the diagnosis of leukemia would highly be relevant because if we’re monitoring some of these people and figuring out who can develop this leukemia and can you do something about it, so this is sort of more on the prevention aspect of leukemia or secondary leukemia, which is also something we are interested in at Cornell and ongoing research is for us.

But the most important things is obviously for patients who actually have the diagnosis of AML, the best available agents as part of clinical trials, the best way to monitor them and design treatments so that we can achieve the best possible results for the patient is what we are striving for at Cornell, and it would be extremely helpful for patients to enroll into these trials and contribute both to their own treatment outcomes and also to the AML community at large.