Treatment Options for Older Patients with Acute Myeloid Leukemia
Martha Arellano, MD, discusses the challenges and uncertainties for older patients with Acute Myeloid Leukemia, treatment options available, ongoing research and when it is important to refer to the specialists at Winship Cancer Institute of Emory University.
Featuring:
Dr. Arellano is a clinical member of the Discovery and Developmental Therapeutics Research Program at Winship Cancer Institute of Emory University. She currently leads the Department of Hematology and Medical Oncology's Fellowship program.
Dr. Arellano earned her medical degree from Emory University School of Medicine in Atlanta, Georgia. She went on to complete her internship and residency at Emory University Hospital in Atlanta, Georgia.
Dr. Arellano's areas of research interest include adoptive immunotherapy for hematopoietic malignancies, novel therapies for acute leukemias and myelodysplastic syndromes, and palliative and supportive care.
She is principal investigator on therapeutic trials for patients with acute leukemias and myelodysplastic syndromes, including immunotherapy and allogeneic transplantation. She is also co-investigator on a tissue repository for hematological disorders, a project that leads to collaborations with scientists within and outside of Emory University.
Martha Arellano, MD
Board certified in hematology, medical oncology and internal medicine, Martha L. Arellano, MD, specializes in the treatment of leukemia and myelodysplastic syndromes. Dr. Arellano started practicing with Emory Healthcare in 2006.Dr. Arellano is a clinical member of the Discovery and Developmental Therapeutics Research Program at Winship Cancer Institute of Emory University. She currently leads the Department of Hematology and Medical Oncology's Fellowship program.
Dr. Arellano earned her medical degree from Emory University School of Medicine in Atlanta, Georgia. She went on to complete her internship and residency at Emory University Hospital in Atlanta, Georgia.
Dr. Arellano's areas of research interest include adoptive immunotherapy for hematopoietic malignancies, novel therapies for acute leukemias and myelodysplastic syndromes, and palliative and supportive care.
She is principal investigator on therapeutic trials for patients with acute leukemias and myelodysplastic syndromes, including immunotherapy and allogeneic transplantation. She is also co-investigator on a tissue repository for hematological disorders, a project that leads to collaborations with scientists within and outside of Emory University.
Transcription:
Melanie Cole (Host): Welcome to Emory Healthcare Rounds. I’m Melanie Cole. Today’s topic is treatment options for older patients with acute myeloid leukemia. My guest is Dr. Martha Arellano. She’s an Associate Professor in the department of Hematology and Medical Oncology at Emory University School of Medicine. And she specializes in the treatment of leukemia. Dr. Arellano explain a little bit about acute myeloid leukemia and when does it typically present?
Martha Arellano, MD (Guest): Yes. So, acute myeloid leukemia is a pretty rare disorder. It presents – it effects patients older than 65 years old and it’s pretty difficult to treat in that population which is why I became interested in it.
Melanie: So, what is the clinical presentation?
Dr. Arellano: Patients can present – the clinical presentation varies from someone presenting in an indolent fashion just with mild symptoms such as fatigue or peripheral blood abnormalities. Or they can present extremely ill with infections, organ dysfunction, hypoxia, or with bleeding or thrombosis related to disseminated intravascular coagulation.
Melanie: So, how is it diagnosed and what are the diagnostic criteria and tools that you might use?
Dr. Arellano: AML is diagnosed generally with a bone marrow biopsy and aspiration. We send the bone marrow sample for assessment of morphology, full cytometric analysis, chromosome analysis. We have a panel – an AML FISH panel which is pretty similar across cancer centers and we also have some new tools that include next generation sequencing for myeloid malignancies which can give us information about specific molecular abnormalities that can help with both the prognosis of AML and also for the potential to use targeted treatments, both in induction, consolidation and maintenance phases of the treatment.
Melanie: So, when we are going to get into some of those but tell us some of the challenges and uncertainties when treating older patients with AML.
Dr. Arellano: So, treating older patients with AML is challenging. There are – I think of it as two things that sort of fight to make this a difficult situation for the patient and the treating physician. And so, one is patient-related factors that include comorbidities. As we know, AML is a disease of the older patient with a median age being around 69 years of age and we know that as we get older, we accumulate more and more comorbidities and some of those are severe enough that they create a situation where the patient will not tolerate what we consider standard induction kind of chemo treatments. In addition to patient-related factors that cause difficulty in us being able to deliver what we consider standard treatments; there are also disease-related factors that are more common in the older patient with AML. Those include poor risk cytogenetics or molecular markers. It also includes more therapy-related types of AML which can make AML in the older patient more resistant to regular chemotherapy. And so, those are some of the challenges that we have to navigate in the treatment of older AML.
Melanie: When you are determining treatment course and as you mentioned comorbidities; speak about how you evaluate some of the baseline measurements of physical performance or cognitive abilities, depression, self-reported function score, things that older patients have going on anyway and how that would affect your treatment decisions.
Dr. Arellano: Yes. So, there are several tools out there that we use, a combination of performance status of the patient and comorbidities of the patient. Putting these factors together can help us to determine which patient is likely to benefit or to tolerate intensive treatments and which patients should be offered lower intensity types of treatments.
Melanie: So, then speak of some of the advancements and innovations in treatment. Tell us about your research and what are your research goals and some ongoing current clinical trials.
Dr. Arellano: So, part of what I do in my clinical practice is determining which patients should or should not receive intensive treatment and determining which patients will not benefit from intensive treatment and should be offered less intensive regimens. We have a cadre of clinical trials for both types of patients. One of the exciting studies that we have here at Emory is a clinical trial that’s sponsored by the Leukemia Lymphoma Society, it’s called Beat AML. This is a clinical trial for newly diagnosed patients with AML, age 60 and older. The trial involves obtaining bone marrow aspirate and biopsy samples at the time of diagnosis. The sample is then sent for genetic analysis and then based on the mutations that are found, the patient is allocated to one of several sub-studies. For example, there is a mutation called IDH1 and for those patients that have IDH1 mutation, they will go on to receive a combination of chemotherapy and an IDH1 inhibitor. For those who have a mutation in P53, they will then go on to get chemotherapy – we are hypomethylating therapy with a drug that has been shown to have activity in P53 mutated AML. The name of the drug is entospletinib. And for those patients who don’t have any targetable mutations, they will go on to receive a combination of hypomethylating therapy and a CD33 – a novel CD33 antibody for treatment.
There is a population that they benefit from a standard type of induction treatment and that would be the patient with favorable cytogenetic and molecular panels. That patient would then be allocated to a standard induction kind of treatment with combination chemotherapy and a targeted agent as well. So, this trial is very exciting for patients because it basically has something for everyone.
Melanie: So, as these genomic investigations of AML have shown that several genes are recurrently mutating, leading to new genomic classifications; give us a little blue print and some promising therapies that you see maybe in the next five or ten years happening.
Dr. Arellano: Yes. So, I think the drug entospletinib, that seems to have a lot of activity in patients with P53 mutation which we know that that carries a very poor prognosis. I think that this drug is very likely to move forward in the future. There’s also – there have been a few treatments that have been FDA approved recently. The 10-15% of patients whose AML harbors an IDH1 mutation now can benefit from a drug that is an IDH1 inhibitor called AG120 or ivosidenib. It was just recently FDA approved for the treatment of relapsed refractory AML with an IDH1 mutation. Now we are investigating it in a randomized clinical trial for patients with newly diagnosed AML. So, I’m very excited about the study. I think it will advance the treatment of older patients with AML. And we would also hope to combine this drug with – for those older patients or for all patients with AML who would be receiving induction chemotherapy. The phase trial that we have currently is for older patients who are not candidates for intensive induction. It uses a hypomethylating agent azacytidine with or without AG120 the IDH1 inhibitor.
The other agent that I think is very exciting is a BCL2 inhibitor called venetoclax. This drug is already approved for the treatment of CLL and myeloma and it has significant activity in AML. So, I think this will likely be a very strong new player in the AML arena.
Melanie: So, in summary Doctor, wrap it up for us, what you would like other physicians to know about acute myeloid leukemia in the older population and when you feel it’s important for them to refer.
Dr. Arellano: So, I think it’s very important to keep in mind that even in the best-case scenario; the older patient with AML is unlikely to be cured with the kinds of standard treatments that are available. So, I would encourage anyone that sees this patient for the first time to refer them for clinical trials as I think that is the only way that we are going to advance the field.
Melanie: It’s great information. Thank you so much for joining us today and sharing your expertise on this complicated and challenging topic. You’re listening to Emory Healthcare Rounds. For more information on the latest advances in medicine please visit www.emoryhealthcare.org/referwinship, that’s www.emoryhealthcare.org/referwinship. This is Melanie Cole. Thanks so much for listening.
Melanie Cole (Host): Welcome to Emory Healthcare Rounds. I’m Melanie Cole. Today’s topic is treatment options for older patients with acute myeloid leukemia. My guest is Dr. Martha Arellano. She’s an Associate Professor in the department of Hematology and Medical Oncology at Emory University School of Medicine. And she specializes in the treatment of leukemia. Dr. Arellano explain a little bit about acute myeloid leukemia and when does it typically present?
Martha Arellano, MD (Guest): Yes. So, acute myeloid leukemia is a pretty rare disorder. It presents – it effects patients older than 65 years old and it’s pretty difficult to treat in that population which is why I became interested in it.
Melanie: So, what is the clinical presentation?
Dr. Arellano: Patients can present – the clinical presentation varies from someone presenting in an indolent fashion just with mild symptoms such as fatigue or peripheral blood abnormalities. Or they can present extremely ill with infections, organ dysfunction, hypoxia, or with bleeding or thrombosis related to disseminated intravascular coagulation.
Melanie: So, how is it diagnosed and what are the diagnostic criteria and tools that you might use?
Dr. Arellano: AML is diagnosed generally with a bone marrow biopsy and aspiration. We send the bone marrow sample for assessment of morphology, full cytometric analysis, chromosome analysis. We have a panel – an AML FISH panel which is pretty similar across cancer centers and we also have some new tools that include next generation sequencing for myeloid malignancies which can give us information about specific molecular abnormalities that can help with both the prognosis of AML and also for the potential to use targeted treatments, both in induction, consolidation and maintenance phases of the treatment.
Melanie: So, when we are going to get into some of those but tell us some of the challenges and uncertainties when treating older patients with AML.
Dr. Arellano: So, treating older patients with AML is challenging. There are – I think of it as two things that sort of fight to make this a difficult situation for the patient and the treating physician. And so, one is patient-related factors that include comorbidities. As we know, AML is a disease of the older patient with a median age being around 69 years of age and we know that as we get older, we accumulate more and more comorbidities and some of those are severe enough that they create a situation where the patient will not tolerate what we consider standard induction kind of chemo treatments. In addition to patient-related factors that cause difficulty in us being able to deliver what we consider standard treatments; there are also disease-related factors that are more common in the older patient with AML. Those include poor risk cytogenetics or molecular markers. It also includes more therapy-related types of AML which can make AML in the older patient more resistant to regular chemotherapy. And so, those are some of the challenges that we have to navigate in the treatment of older AML.
Melanie: When you are determining treatment course and as you mentioned comorbidities; speak about how you evaluate some of the baseline measurements of physical performance or cognitive abilities, depression, self-reported function score, things that older patients have going on anyway and how that would affect your treatment decisions.
Dr. Arellano: Yes. So, there are several tools out there that we use, a combination of performance status of the patient and comorbidities of the patient. Putting these factors together can help us to determine which patient is likely to benefit or to tolerate intensive treatments and which patients should be offered lower intensity types of treatments.
Melanie: So, then speak of some of the advancements and innovations in treatment. Tell us about your research and what are your research goals and some ongoing current clinical trials.
Dr. Arellano: So, part of what I do in my clinical practice is determining which patients should or should not receive intensive treatment and determining which patients will not benefit from intensive treatment and should be offered less intensive regimens. We have a cadre of clinical trials for both types of patients. One of the exciting studies that we have here at Emory is a clinical trial that’s sponsored by the Leukemia Lymphoma Society, it’s called Beat AML. This is a clinical trial for newly diagnosed patients with AML, age 60 and older. The trial involves obtaining bone marrow aspirate and biopsy samples at the time of diagnosis. The sample is then sent for genetic analysis and then based on the mutations that are found, the patient is allocated to one of several sub-studies. For example, there is a mutation called IDH1 and for those patients that have IDH1 mutation, they will go on to receive a combination of chemotherapy and an IDH1 inhibitor. For those who have a mutation in P53, they will then go on to get chemotherapy – we are hypomethylating therapy with a drug that has been shown to have activity in P53 mutated AML. The name of the drug is entospletinib. And for those patients who don’t have any targetable mutations, they will go on to receive a combination of hypomethylating therapy and a CD33 – a novel CD33 antibody for treatment.
There is a population that they benefit from a standard type of induction treatment and that would be the patient with favorable cytogenetic and molecular panels. That patient would then be allocated to a standard induction kind of treatment with combination chemotherapy and a targeted agent as well. So, this trial is very exciting for patients because it basically has something for everyone.
Melanie: So, as these genomic investigations of AML have shown that several genes are recurrently mutating, leading to new genomic classifications; give us a little blue print and some promising therapies that you see maybe in the next five or ten years happening.
Dr. Arellano: Yes. So, I think the drug entospletinib, that seems to have a lot of activity in patients with P53 mutation which we know that that carries a very poor prognosis. I think that this drug is very likely to move forward in the future. There’s also – there have been a few treatments that have been FDA approved recently. The 10-15% of patients whose AML harbors an IDH1 mutation now can benefit from a drug that is an IDH1 inhibitor called AG120 or ivosidenib. It was just recently FDA approved for the treatment of relapsed refractory AML with an IDH1 mutation. Now we are investigating it in a randomized clinical trial for patients with newly diagnosed AML. So, I’m very excited about the study. I think it will advance the treatment of older patients with AML. And we would also hope to combine this drug with – for those older patients or for all patients with AML who would be receiving induction chemotherapy. The phase trial that we have currently is for older patients who are not candidates for intensive induction. It uses a hypomethylating agent azacytidine with or without AG120 the IDH1 inhibitor.
The other agent that I think is very exciting is a BCL2 inhibitor called venetoclax. This drug is already approved for the treatment of CLL and myeloma and it has significant activity in AML. So, I think this will likely be a very strong new player in the AML arena.
Melanie: So, in summary Doctor, wrap it up for us, what you would like other physicians to know about acute myeloid leukemia in the older population and when you feel it’s important for them to refer.
Dr. Arellano: So, I think it’s very important to keep in mind that even in the best-case scenario; the older patient with AML is unlikely to be cured with the kinds of standard treatments that are available. So, I would encourage anyone that sees this patient for the first time to refer them for clinical trials as I think that is the only way that we are going to advance the field.
Melanie: It’s great information. Thank you so much for joining us today and sharing your expertise on this complicated and challenging topic. You’re listening to Emory Healthcare Rounds. For more information on the latest advances in medicine please visit www.emoryhealthcare.org/referwinship, that’s www.emoryhealthcare.org/referwinship. This is Melanie Cole. Thanks so much for listening.