Selected Podcast
Research Underway to Tailor Therapies for Acute Myeloid Leukemia
Todd Druley, MD, PhD, discusses the latest research underway to tailor therapies for Acute Myeloid Leukemia, and how advancements and innovations in treatment have lead to the Hyundai Hope on Wheels Quantum Award.
Featured Speaker:
Learn more about Todd Druley, MD, PhD
Todd Druley, MD, PhD
Todd Druley, MD, PhD cares for children with blood diseases.Learn more about Todd Druley, MD, PhD
Transcription:
Melanie Cole (Host): Recent significant improvements in the understanding of the biology and genetics for acute myeloid leukemia is now being translated into new therapies for this disease. My guest is Dr. Todd Druley. He’s a Washington University pediatric hematologist and oncologist at St. Louis Children’s Hospital. Dr. Druley, explain a little bit about acute myeloid leukemia, really what is it and who does it affect?
Dr. Todd Druley (Guest): Absolutely, thank you for having me today. So there’s different types of leukemia in children. The most common is acute lymphoblastic leukemia or ALL and that’s been one of the major success stories of modern medicine. We now cure over 85% of those children, but the other type of leukemia is AML, acute myeloid leukemia and that has not enjoyed the same type of success and it’s a leukemia that derived from a different type of white blood cell, which is an infection fighting cell.
Melanie: Then tell us a little bit about the clinical presentation and when would this show up? What are some of the signs and symptoms?
Dr. Druley: There’s a peak of AML in infancy believe it or not and then sort of a gradual rise throughout the lifetime. It’s actually the most common type of leukemia in adults and the cure rates for AML are only around 65%, 60% to 65%, so people will notice that their child may have a lot of sweating, they’re losing weight, they bruise quite easily, they have a lot of confusion, headaches, things like that, pretty common signs for an acute leukemia, and believe it or not, for AML whether you’re two years old or 92 years old, the fundamental treatment that everyone receives was developed in 1973 and hasn’t changed substantially in 45 years and we think that’s quite ridiculous actually and we’re looking to improve it.
Melanie: Well then let’s go on about those lines. Speak about the Hyundai Hope on Wheels Quantum Award that you received and how it will help further your research into treatments.
Dr. Druley: Yes, I was very honored to be one of three Hyundai Hope on Wheels Quantum Award recipients in 2018. So this is a one million dollar award that Hyundai developed last year and that was their first year of this award and so we were lucky to get it this year, and I would just like to point out that Hyundai has been a very generous supporter of our work through multiple awards since 2012. So what this award is going to do is help my team, which is taking the largest pediatric AML study that’s ever been done through the Children’s Oncology Group, so that is a group of pediatric cancer treatment centers throughout North America and some foreign countries as well. It took about seven or eight years. They finished the study in 2017. It’s got about 1,000 children that were entered on that study, looking for new treatment combinations to improve outcomes. So what we were able to do is we’ve developed some DNA and RNA sequencing technology to try to improve surveillance and selection of more precision based treatments for children with AML, and so we’re going back retrospectively, taking the samples that were collected on that study and applying our sequencing strategies to try and demonstrate how we can improve the current status quo and how looking back one might have made different treatment selections had they known that information ahead of time, which would then set the table for us doing this prospectively going forward.
Melanie: Dr. Druley, who’s involved in your research? How will this award leverage a multidisciplinary team of pediatric leukemia experts to study this mutation and improve treatments and survival rates?
Dr. Druley: So yeah, very blessed to work with a strong team of pediatric leukemia experts. So the study itself was originally started in 2010 by Richard Aplenc at Children’s Hospital of Philadelphia and so working with folks in Seattle and Philadelphia, we’ve got a computational team at Nemours Children’s Hospital in Delaware, working with statisticians in Los Angeles. So we’re taking samples from multiple different countries, working with folks all across the country to see how we can better improve these outcomes for these children.
Melanie: So tell us a little bit about how this works and what are some of the intended results? I mean obviously we know that it is for better treatment and better results, but what are you looking to accomplish in the very near future? Give us a little predicter of treatment response.
Dr. Druley: So the current methods, we know that when you have residual leukemia after you’ve received your first month of treatment, then your likelihood of a cure is much worse than if all of your leukemia has been eradicated. But the historic methods for doing that, they measure the leukemia a little bit differently than what we’re trying to do, and they just give you a yes or no answer. So yes there’s leukemia still around or no the leukemia is gone, and if the leukemia is still around that’s a really bad sign and it causes the oncologist to then give the child larger, more potent doses of really nonspecific and fairly toxic chemotherapy. Now what we’re proposing to do is offer a sequencing based approach. So we look at 80 different genes, all involved in AML, and by doing that, no only can we match the sensitivity, we can tell you just as good as the other methods if the cells are there or not but what we give you is a digital readout of the genes that are actually mutated. So the advantage that we’re hoping to provide is the physician can say okay, yeah there’s residual disease there, but instead of giving the higher doses of nonspecific toxic treatment, this gene has a very precise agent that’s available, we can get that, and we can give this to this child and reduce the toxicity and improve the outcome at the same time.
Melanie: So by these genomic investigations, are you hoping that this leads to new classifications and predictive markers and then thereby new therapeutic targets?
Dr. Druley: Absolutely, so right now we’re very focused on looking for residual disease after treatment, but I think our sequencing approach would actually enable the physicians to use this at the time of diagnosis so then you wouldn’t run the risk of just starting with these nonspecific therapies. What if you knew all the mutations from day one, and you could say okay, let’s abandon these agents that are unlikely to work in favor of other agents that are much more likely to be affective, and by doing so we’re hopeful that that would improve the percentage of children that are cured but also significantly reduce the long term consequences that come from this intensive treatment they receive.
Melanie: And as we wrap up Dr. Druley, tell other providers what you would like them to know about acute myeloid leukemia, your Hyundai Hope on Wheels Quantum Award and how this will help further research for children as far as treatment and outcome results.
Dr. Druley: Well I’m very proud of the team that we have here at St. Louis Children’s Hospital. The Siteman Cancer Center is one of the top centers in the country and the branch of Siteman that treats children is called Siteman Kids. It exists within the Children’s Hospital. We’ve got an amazing team of scientists and clinicians and I think being competitive for these types of awards such as the Hyundai Quantum Award shows the caliber of work, not just myself, but our entire team is doing and we’re really working to push the entire pediatric cancer community to make more precision therapies for children. A lot of the drugs that get developed are not geared towards kids because thankfully pediatric cancer by definition is a rare disease but they often need precise treatments that are different from adult treatments and until we know what those certain genes and markers are, we’re not going to have those agents available, so we’re really pushing the entire community to move in that direction, and I think this shows that we’re committed to that goal.
Melanie: It certainly does and congratulations again on such a prestigious award. Thank you again for joining us today. A physician can refer a patient by calling Children’s Direct Physician Access line at 1-800-678-HELP, that’s 1-800-678-4357. You’re listening to Radio Rounds with St. Louis Children’s Hospital. For more information on resources available at St. Louis Children’s Hospital, you can go to stlouischildrens.org, that’s stlouischildrens.org. This is Melanie Cole, thanks so much for listening.
Melanie Cole (Host): Recent significant improvements in the understanding of the biology and genetics for acute myeloid leukemia is now being translated into new therapies for this disease. My guest is Dr. Todd Druley. He’s a Washington University pediatric hematologist and oncologist at St. Louis Children’s Hospital. Dr. Druley, explain a little bit about acute myeloid leukemia, really what is it and who does it affect?
Dr. Todd Druley (Guest): Absolutely, thank you for having me today. So there’s different types of leukemia in children. The most common is acute lymphoblastic leukemia or ALL and that’s been one of the major success stories of modern medicine. We now cure over 85% of those children, but the other type of leukemia is AML, acute myeloid leukemia and that has not enjoyed the same type of success and it’s a leukemia that derived from a different type of white blood cell, which is an infection fighting cell.
Melanie: Then tell us a little bit about the clinical presentation and when would this show up? What are some of the signs and symptoms?
Dr. Druley: There’s a peak of AML in infancy believe it or not and then sort of a gradual rise throughout the lifetime. It’s actually the most common type of leukemia in adults and the cure rates for AML are only around 65%, 60% to 65%, so people will notice that their child may have a lot of sweating, they’re losing weight, they bruise quite easily, they have a lot of confusion, headaches, things like that, pretty common signs for an acute leukemia, and believe it or not, for AML whether you’re two years old or 92 years old, the fundamental treatment that everyone receives was developed in 1973 and hasn’t changed substantially in 45 years and we think that’s quite ridiculous actually and we’re looking to improve it.
Melanie: Well then let’s go on about those lines. Speak about the Hyundai Hope on Wheels Quantum Award that you received and how it will help further your research into treatments.
Dr. Druley: Yes, I was very honored to be one of three Hyundai Hope on Wheels Quantum Award recipients in 2018. So this is a one million dollar award that Hyundai developed last year and that was their first year of this award and so we were lucky to get it this year, and I would just like to point out that Hyundai has been a very generous supporter of our work through multiple awards since 2012. So what this award is going to do is help my team, which is taking the largest pediatric AML study that’s ever been done through the Children’s Oncology Group, so that is a group of pediatric cancer treatment centers throughout North America and some foreign countries as well. It took about seven or eight years. They finished the study in 2017. It’s got about 1,000 children that were entered on that study, looking for new treatment combinations to improve outcomes. So what we were able to do is we’ve developed some DNA and RNA sequencing technology to try to improve surveillance and selection of more precision based treatments for children with AML, and so we’re going back retrospectively, taking the samples that were collected on that study and applying our sequencing strategies to try and demonstrate how we can improve the current status quo and how looking back one might have made different treatment selections had they known that information ahead of time, which would then set the table for us doing this prospectively going forward.
Melanie: Dr. Druley, who’s involved in your research? How will this award leverage a multidisciplinary team of pediatric leukemia experts to study this mutation and improve treatments and survival rates?
Dr. Druley: So yeah, very blessed to work with a strong team of pediatric leukemia experts. So the study itself was originally started in 2010 by Richard Aplenc at Children’s Hospital of Philadelphia and so working with folks in Seattle and Philadelphia, we’ve got a computational team at Nemours Children’s Hospital in Delaware, working with statisticians in Los Angeles. So we’re taking samples from multiple different countries, working with folks all across the country to see how we can better improve these outcomes for these children.
Melanie: So tell us a little bit about how this works and what are some of the intended results? I mean obviously we know that it is for better treatment and better results, but what are you looking to accomplish in the very near future? Give us a little predicter of treatment response.
Dr. Druley: So the current methods, we know that when you have residual leukemia after you’ve received your first month of treatment, then your likelihood of a cure is much worse than if all of your leukemia has been eradicated. But the historic methods for doing that, they measure the leukemia a little bit differently than what we’re trying to do, and they just give you a yes or no answer. So yes there’s leukemia still around or no the leukemia is gone, and if the leukemia is still around that’s a really bad sign and it causes the oncologist to then give the child larger, more potent doses of really nonspecific and fairly toxic chemotherapy. Now what we’re proposing to do is offer a sequencing based approach. So we look at 80 different genes, all involved in AML, and by doing that, no only can we match the sensitivity, we can tell you just as good as the other methods if the cells are there or not but what we give you is a digital readout of the genes that are actually mutated. So the advantage that we’re hoping to provide is the physician can say okay, yeah there’s residual disease there, but instead of giving the higher doses of nonspecific toxic treatment, this gene has a very precise agent that’s available, we can get that, and we can give this to this child and reduce the toxicity and improve the outcome at the same time.
Melanie: So by these genomic investigations, are you hoping that this leads to new classifications and predictive markers and then thereby new therapeutic targets?
Dr. Druley: Absolutely, so right now we’re very focused on looking for residual disease after treatment, but I think our sequencing approach would actually enable the physicians to use this at the time of diagnosis so then you wouldn’t run the risk of just starting with these nonspecific therapies. What if you knew all the mutations from day one, and you could say okay, let’s abandon these agents that are unlikely to work in favor of other agents that are much more likely to be affective, and by doing so we’re hopeful that that would improve the percentage of children that are cured but also significantly reduce the long term consequences that come from this intensive treatment they receive.
Melanie: And as we wrap up Dr. Druley, tell other providers what you would like them to know about acute myeloid leukemia, your Hyundai Hope on Wheels Quantum Award and how this will help further research for children as far as treatment and outcome results.
Dr. Druley: Well I’m very proud of the team that we have here at St. Louis Children’s Hospital. The Siteman Cancer Center is one of the top centers in the country and the branch of Siteman that treats children is called Siteman Kids. It exists within the Children’s Hospital. We’ve got an amazing team of scientists and clinicians and I think being competitive for these types of awards such as the Hyundai Quantum Award shows the caliber of work, not just myself, but our entire team is doing and we’re really working to push the entire pediatric cancer community to make more precision therapies for children. A lot of the drugs that get developed are not geared towards kids because thankfully pediatric cancer by definition is a rare disease but they often need precise treatments that are different from adult treatments and until we know what those certain genes and markers are, we’re not going to have those agents available, so we’re really pushing the entire community to move in that direction, and I think this shows that we’re committed to that goal.
Melanie: It certainly does and congratulations again on such a prestigious award. Thank you again for joining us today. A physician can refer a patient by calling Children’s Direct Physician Access line at 1-800-678-HELP, that’s 1-800-678-4357. You’re listening to Radio Rounds with St. Louis Children’s Hospital. For more information on resources available at St. Louis Children’s Hospital, you can go to stlouischildrens.org, that’s stlouischildrens.org. This is Melanie Cole, thanks so much for listening.