What Is MRD-Positive Acute Myeloid Leukemia?

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What Is MRD-Positive Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about MRD-positive AML? Dr. Catherine Lai from Penn Medicine discusses minimal residual disease (MRD). Learn about the meaning of MRD, complete remission, and MRD testing methods.

[ACT]IVATION TIP from Dr. Lai: “Ask if MRD testing can be done on your bone marrow biopsy at the time at which you or after you’ve had your chemotherapy.” 

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Transcript: 

Art:

Dr. Lai, what is MRD-positive AML?

Dr. Catherine Lai:

So, that’s a really good question. And to answer that question, I’m going to actually answer a different question, which is, What is the definition of complete remission? So the definition of complete remission is when we do a bone marrow biopsy, and we have less than 5 percent of those blasts or leukemia cells in the bone marrow, and that is also in the setting of a relatively normal immune system or normal other blood counts have improved, so that your neutrophil count is above 1,000, and your platelet count is above 100,000. So, MRD, which stands for measurable residual disease, means that you’re in complete remission, so you have less than 5 percent blasts, but you’re more than zero.

And we, in general, when patients who are MRD-positive, we know that if you were to do nothing, that those patients have a high likelihood of relapse. We know for the patients who are going to transplant, if you’re MRD-positive before transplant, those patients also have a higher likelihood of relapsing after transplant. And so we tend to monitor it if possible…the tricky thing is, is that there is not a standard way to measure MRD testing as of yet, the common approaches are right now are with either flow cytometry or with PCR or next-generation sequencing, if you have a particular targeted mutation that we can follow.

So your activation from that standpoint is to ask if MRD testing can be done on your bone marrow biopsy at the time at which you or after you’ve had your chemotherapy. 

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What Is FLT3-Mutated Acute Myeloid Leukemia?

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What Is FLT3-Mutated Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

Some acute myeloid leukemia (AML) patients may have an FLT3 mutation. Dr. Catherine Lai from Penn Medicine shares insight about the two types of FLT3 mutation, treatment options for FLT3-mutated AML, and progress in research

[ACT]IVATION TIP from Dr. Lai: “Ask your oncologist, if your FLT3 mutation testing was done, ask which type of mutation they have, if it’s the ITD or TKD, if they are FLT3-positive and what the drug options are available for them.”

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Transcript: 

Art: 

Dr. Lai, what is FLT3 mutated AML and what treatment options do patients with FLT3 AML have?

Dr. Catherine Lai: 

Yeah, so FLT3, FLT3 mutations occur in about 25 percent to 30 percent of patients. There are two different types of FLT3 mutations. There’s a FLT3, the ITD mutation and the FLT3, the TKD mutation. They just are there, different parts of the mutation on different parts of the cell, and so how I think about that is, if you think of a leukemia cell and each leukemias has a different color-coded flag, and so the FLT3 mutation I think of is just having a specific color coding, and while a FLT3 mutation in general does predict for a worse prognosis for patients, we do have targeted treatments. In a newly diagnosed setting, we have midostaurin (Rydapt), which is added to intensive chemotherapy for those fit enough to tolerate it. 

And in the relapsed refractory setting, we have a medication called gilteritinib (Xospata), which is given as a single agent, so a chemo pill, and that was compared to all types of chemotherapy, both intensive and low intensive chemotherapy, and that pill alone and the refractory and relapsed setting was better than either of the chemotherapies alone, so we’ve made a lot of progress for the FLT3-mutated patients to the majority of those patients end up going to transplant if possible, and so there are studies that are looking at FLT3 inhibitors in the post-transplant setting to also help improve long-term survival and overall survival. So the activation tip from that standpoint, that is to ask your oncologist, if your FLT3 mutation testing was done, ask which type of mutation they have, if it’s the ITD or TKD, if they are FLT3-positive and what the drug options are available for them. 

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What Are the Latest Acute Myeloid Leukemia Therapies?

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What Are the Latest Acute Myeloid Leukemia Therapies? from Patient Empowerment Network on Vimeo.

What are the latest treatments in acute myeloid leukemia (AML)? Dr. Catherine Lai from Penn Medicine discusses the increase in available AML treatments. Learn about combination therapies and treatment options for patients with IDH1, IDH2, and FLT3 mutations.

[ACT]IVATION TIP from Dr. Lai: “Ask your physician and your oncologist when you’re talking with them about what all the newest therapies are and what would be specifically the best treatment for their specific leukemia with respect to the different mutations.”

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Transcript: 

Art:

Dr. Lai, for newly diagnosed AML patients, what are the latest available therapies?

Dr. Catherine Lai:

That’s a great question. The last, I would say, a handful of years have really seen a dramatic increase in the number of new treatment options for AML patients, specifically since 2017, the FDA has approved 10 new drugs for AML, that’s both for patients who are newly diagnosed and in the relapsed refractory setting.

And so what I would say is that we break our patients into two different categories in terms of being able to tolerate intensive chemotherapy versus non-intensive chemotherapy, and as well as looking at specifically targeted mutations that patients may have so that we can better understand the disease but also treat these patients more specifically to try to maximize efficacy while minimizing toxicity. 

And so specifically, I would say for patients who have FLT3 mutations, there are drugs such as midostaurin (Rydapt) and gilteritinib (Xospata), there are drugs for mutations in IDH1 and IDH2, enasidenib (Idhifa) and ivosidenib (Tibsovo) and recently, or in December of  2022, olutasidenib (Rezlidhia) was also approved for IDH1-mutated patients as well.

We have a general targeted agent that’s an oral chemotherapy that probably has made the biggest difference in how we treat patients called venetoclax (Venclexta), and that’s used in combination with azacitidine (Onureg) or decitabine (Dacogen), or low dose cytarabine (Cytosar).

Although most commonly in the United States, we use azacitidine or decitabine in combination with the venetoclax, and that I think is really what I’d say has been practice changing for the most part, in terms of both increasing the complete remission rates as well as the overall survival for these patients. So I would say there are a lot of new drugs. It is all very exciting.

The biggest activation tip in terms of takeaways is to ask your physician and your oncologist when you’re talking with them about what all the newest therapies are and what would be specifically the best treatment for their specific leukemia with respect to the different mutations.

Art:

Okay. Dr. Lai, what are the latest approaches to combination chemotherapy to treat AML?

Dr. Catherine Lai:

So, the latest approaches for combination chemotherapy would be in the combination of a hypomethylating agent, azacitidine or decitabine in combination with venetoclax. This is the most practice-changing combination that has been approved since 2017 to 2018, and now more recently, what’s been happening is now looking, so we call that a doublet, and now it’s been looking at…what we’ve been studying is now whether or not triplets are more effective, when we do have triple combinations, we do see an increase in toxicity and so on, we haven’t come up with the right algorithm in terms of what that exact formula should be, but often I think about it in kind of a three-fold in terms of wins the right time, what’s the right combination, and how do we see in the drugs, and I think the sequencing is the biggest thing that we don’t yet know, and how do we combine the two different..two different drugs in a way, and how do we give them in a way that will maximize efficacy, will minimize the toxicity, so as an example is, Do we give two drugs for a specific period of time, and then after some determined time point, do we…

And change it to a different set of combination of drugs to make sure that patients are getting the most benefit of the drugs, and we don’t know that yet, but I think that that’s where the general direction…where the landscape is heading, so the activation tip I would take home from this is just to have a conversation with your physician about potential clinical trials and how combination therapies are being used. 

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How an AML Survivor’s Resilience Saved Her Life

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How an AML Survivor’s Resilience Saved Her Life from Patient Empowerment Network on Vimeo.

Acute myeloid leukemia (AML) patient Sasha’s symptoms were dismissed multiple times before her diagnosis. Watch as she shares the story of her cancer journey from diagnosis through treatment as a BIPOC patient – and her advice to other patients to receive equitable and optimal care.

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Transcript:

My name is Sasha. I live in Brawley, California. In 2017, I was diagnosed with acute myeloid leukemia (AML). When I first noticed signs and symptoms, I wasn’t sure what was wrong, but I knew I didn’t feel like myself. I was really tired, fatigued, and getting random little bruises everywhere.

I went to my local hospital three separate times, and each time they didn’t take my concerns seriously. I’d sit in a room for hours until someone finally walked by, and I’d ask to see an expert. Staff members assumed I had already been discharged without even know what my “diagnosis” was.

When I was finally seen, they ran a few tests and sent me home saying it was just anemia or a blood disorder and if I took whatever medication they prescribed, I’d be okay. I felt very ignored. As a plus size woman of color, I’ve been told all my life from medical professionals, no matter what my issue was, if I just lost weight, I’d be fine. There were even moments when the staff assumed I didn’t know English and rudely commented behind office doors. Ironically, they thought I couldn’t understand when English is actually my first language. I knew there had to be a better explanation, but I let the medical staff push my concerns aside.

Finally, after a battery of tests, I remember the doctor walking in the room. He was acting very sad and very concerned. He put his hand on my shoulder and said, “I’m really sorry to tell you, but you have leukemia.” The day of my diagnosis, I started chemotherapy and began experiencing several side effects. One of the hardest things after being diagnosed was losing my hair. Not seeing my family was equally difficult, because my parents didn’t have the gas money or transportation.

After the full week of chemo, we had to wait for results to see if the leukemia cells were gone. It was mostly a waiting game. Finally, they told me the chemotherapy worked and that the leukemia cells were gone. But in order for them to stay gone, I would need to move forward with the bone marrow transplant.

Fortunately, the results came a few months later indicating the transplant was working. I am happy to report I’m cancer-free, but the road has not been easy. If there’s one thing I learned from my situation, it’s always trust your gut. If anyone knows your body, it’s you. My advice to other AML patients:

  • Trust your gut and listen to your body. If you feel something is wrong, fight for yourself
  • Get yourself a good healthcare team who will also fight for you and your needs
  • Make friends and talk to others in the cancer community
  • Mental health is just as important as physical health. It’s okay to talk to someone professional and ask for help

Remember, you are in control of your journey and your future. These actions are key to staying on your path to empowerment.