Dr. John Byrd, University of Cincinnati Cancer Center hematologist, talks about a new treatment for blood and bone marrow cancer.
Interview conducted by Ivanhoe Broadcast News in 2022.
Interviewer: All good. Dr. Byrd, the first question is the easy one. I just want you to say and spell both your first and last name for me.
What does AML stand for and what is it?
BYRD: AML stands for acute myeloid leukemia and it is the most common type of leukemia that’s diagnosed in adults. And the foremost important thing is a better term would be acute myeloid leukemias because although it has one name, they’re probably 15-20 different types of AML. And this is a disease that patients are diagnosed with very acutely. So they can come into their doctor with fatigue, say muscle aches, fever, have a blood count shock, and there’s something clearly wrong. And often they’ll be home and when the blood test comes back the doctor will call them into the emergency room. And in the past, they would get admitted very, very quickly and receive therapy that was very intensive and have to stay in the hospital for a month. This is receiving that therapy, disrupting their whole life and long-term it’s a disease that before we had some of the newer therapies, less than 10% of patients could be cured or were alive five months after, sorry, five years after receiving the initial treatment for it.
Was bone marrow transplant the only option?
BYRD: So the two options that are typically used, most patients are older and are not candidates for bone marrow transplant. We have adopted new ways of doing bone marrow transplant where intensive therapy is not given before the transplant. Say for most patients with AML, that’s the only curative therapy. For a subset, we can give very intensive chemotherapy. But again, this chemotherapy is really, really tough on patients. They have to stay in the hospital for months at a time but are not able to work. About 10-20% of people going through the therapy will die as a consequence of the therapy. So something I think we’ll look back 100 years from now when we’re using, we’re treating everything with novel technology and say this was barbaric.
What are you and your colleagues looking at here in the lab?
BYRD: Our group is part of a large consortium that is looking at new ways of treating AML. And this is a clinical trial sponsored by the Leukemia & Lymphoma Society that the University of Cincinnati is part of that took the approach of rather than seeing AML as one disease, that AML is actually 15-20 diseases based upon the genetic markers of the disease. Because as I said before, when people are diagnosed with AML, they would come in and everybody would be treated the same way. So imagine if you had prostate cancer and you’ve got treated with a colon cancer therapy, it’s not going to work. And this is part of the hypothesis that if we took all of the information about AML into account, the genetics, the cytogenetics and instead you have Type A AML and therefore we’re going to treat you with a targeted therapy toward Type A, you would better than just a random therapy. And this, it sounds pretty simple, but for many years, AML it wasn’t recognized that it was multiple diseases and it was treated with a general therapy that was very toxic. The BDML study address this by bringing patients in, getting all of the genetic information, and then using that to assign patients to therapy. The study started in 2016 and it was a partnership that the Leukemia and Lymphoma Society brokered between universities like the University of Cincinnati and many other lead universities that take care of patients with AML pharmaceutical companies, the FDA, to address this question, can we pick a therapy for the AML, do it safely and have better patient outcomes? And about two years ago, a little less than two years ago, we reported the first results of this, which showed two remarkable things. First, when we looked at people who came into the study where we waited and got all the information and then made an educated decision toward treatment A, B, or C based upon the type of AML they had, it was safe to do. So there was not an adverse outcome, and the patients that we did that for did much, much better both early on and long-term in terms of their survival than patients who just received standard therapy that wasn’t matched with their disease. The coolest part of the study though was there were small subsets of AML that we identified that had genetic markers directed toward IDH1 or IDH2 mutations where there was a pill medicine that those patients could take. And the story typically of AML of having to stay in the hospital for months, receive transfusions, getting real sick. The patients that went on this study, that were in this group, were able to take a pill and stayed on that pill. A subset of those patients never even came into the hospital to receive their therapy. They were all outpatient. They never received chemotherapy. There’s a subset of those patients that are still alive in remission having never taking chemotherapy for their AML based upon the treatment approach that was piloted, it’d be a male.
Where are you and your colleagues now in the lab? What are you focusing your test on?
BYRD: After proving that we could do this, the group now is looking at because most type of AML, it’s going to require combination approaches. It’s developing targeted therapies toward multiple genetic markers and giving several targeted medicines together. We can prevent resistance from developing and ultimately cure more patients with patient-friendly therapy. The BDML study is also looking to expand. Initially we were focused on patients who are newly diagnosed and we’re extending our studies to patients who have received other therapies for AML and their diseases come back and then lastly, we’re working with the National Cancer Institute in helping them plan a national study that the National Cancer Institute will find called myelin match. That’s taking this approach to a bigger level. It’s not going to be at just ten to 15 sites that are part of BDML. But it’s going to be at most of the cancer centers and hospitals around the country. Again, that’s another exciting part of beat BDML leukemia lymphoma societies study is that we’re able to take a concept from a small number of leading institutions like the University of Cincinnati and the other principal sites to a national platform where this will be available for all patients across the United States and Canada.
What are the implications of having some of this information that you have?
BYRD: I think every time we make an advance in treating a type of cancer by using our genetic information and showing outcomes are better. We chip away at the number of patients that are both dying from cancer, but also the number of patients that go through either unnecessarily toxic therapy or therapies that aren’t going to work. Many of the mutations that exist in AML where we develop targeted therapies. Those mutations and I was giving the example of the IDH2 mutations. Those are in brain tumors, those rem lymphomas, those are in glandular carcinoma different types of cancers where once a medicine gets approved in one application, it can potentially be applied to a lot of other types of cancers that have that same mutation but might be in a different part of the body.
Is that the way in your mind cancer treatment is going? It’s about treating the exact diseases, treating the mutation?
BYRD: I think a component of cancer therapy is going out way of treating of it being agnostic to how the tumor looks like under the microscope or where it originates but the mutation. I also think that we were using those targeted therapies together with treatments that awaken the immune system. Because cancer develops in AML all types, all cancers develop in part because the outsmart the immune system. When you can retrain the immune system with medications together with a targeted therapy, that’s often where you have the biggest outcome in terms of not only patients responding, but potentially being cured of their cancer.
Are you still at a site that is recruiting?
BYRD: It’s still ongoing. The University of Cincinnati is recruiting to beat AML and the university plays a major role. I’m the Chief Medical Officer for the entire study. One of the principles and we, along with the along with the other sites, are actively toward different trials. Both doing pilots to facilitate into the bigger National Cancer Institute study as well as looking at newer molecules that are being tested in relapse. Our laboratory is looking at about 5-7 different targets that are new and relevant to AML. The path of drug development starts with getting samples from patients often that participate in trials where we test the compounds in the laboratory, see if the compounds cause the leukemia cells to die. Then we test them in mouse models of leukemia. Mice that are genetically engineered to develop leukemia and we test the drugs and the drugs work in those two settings. Then they move to the next level of testing and ultimately get into early phase one clinical trials where they’re tested in AML.
Is there anything that I didn’t ask you about the AML that you want people to know?
BYRD: I think say, compared to where things were several decades ago. Much progress has been made in understanding the biology and the new therapies. That’s come from both the research that all of us have funded who pay taxes that the National Cancer Institute and other organizations leukemia lymphoma society support. But also many patients that participate in clinical trials to move the field forward. Because of that, there’s more optimism in AML than there ever has been before. We still have a long ways to go compare it to the other leukemias and the other types of leukemias that we’re, we have much better therapies. But we’re going to get there. Because there are a lot of exciting things that are coming forward.
How many people in the U.S. are diagnosed?
BYRD: About 22,000 a year.
How many deaths?
BYRD: It’s about 14,000 a year. The average age is about 67.
END OF INTERVIEW
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