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Transcript

((Voice Over))
Welcome to the presentation titled “AML-MRC: Definition, Presentation, and Risk.”

VYXEOS is indicated for the treatment of adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes.

VYXEOS has different dosage recommendations than other daunorubicin and cytarabine-containing products. Do not interchange with products containing these ingredients.

Do not use in patients with a history of serious hypersensitivity reactions to cytarabine, daunorubicin or any other components of VYXEOS.

This segment is presented by Sandra Kurtin, a nurse practitioner at the University of Arizona Cancer Center in Tucson, Arizona. She will walk through an overview of AML-MRC or acute myeloid leukemia with myelodysplasia-related changes.

((Sandra Kurtin, RN, MS, AOCN, ANP-C))

This is that new World Health Organization for AML with myelodysplastic-related changes or MRC. So, by definition, to make the diagnosis of AML -- and this came out of the 2008 criteria -- they switched the threshold for blasts from 30% to 20%. So now, we say, "If you have greater than or equal to 20% blasts in the peripheral blood or bone marrow, you by definition have AML.”

And then we're going to say, "Okay, could it be that it's one of these treatment-related or myelodysplasia-related changes…

…that brought you to AML?"

So, to make the diagnosis of AML-MRC, you have to have a documented previous hematologic malignancy -- in this case MDS, or the MDS/MPN crossover. MDS/MPN crossover is MDS -- myelodysplastic syndrome -- and myeloproliferative neoplasms.

The endpoint for all of those diseases is AML.

Morphological detection of multilineage dysplasia in greater than 50% of the cells, so this can be a tricky diagnosis to make, and it does take a trained hematopathologist to really be able to detect those changes. It needs to be present in greater than 2 cell lines excluding…

…these rare cases of mutations of NPM1 or biallelic CEBPA, which are 2 of the molecular markers commonly found in de novo AML.

And then you see these balanced and unbalanced abnormalities. So, the unbalanced abnormalities are usually deletions or additions. And so, you see the 7s and the 5s here very commonly -- chromosome 7 and 5.

Balanced abnormalities are translocations, so you're basically taking part of one chromosome and another one, and you're translocating them.

So, these are the common attributes that the hematopathologist is looking for when they're evaluating that case.

Here's our second case. So, this is a AML-MRC patient.

These tend to be older patients; average age at diagnosis depending on which data you look at…

…is somewhere in the mid-70s, so some are between 73 and 76 depending on the data set.

MDS-related cytogenetic abnormalities, commonly 5s and 7s. You also see 17p, which is not good ever in any situation ... we all know 17p is bad.

Multilineage dysplasia…

…talking about myeloid ... myeloid is where you get your red blood cells, white blood cells and platelets, from that myeloid lineage. So, what we're looking at -- is it just the red cell lineage -- erythrocytes; is it platelets -- thrombocytes, or megakaryocytic changes; or does it include the granulocytes, which are the myeloid white blood cells? So, you're looking for these different abnormalities.

Again, poor outcomes when associated with cytogenetic abnormalities.

So, therapy-related and secondary AML are associated with poor outcomes.

I'm finishing up work on my Ph.D., collecting my data right now, and took a lot of statistics, but basically the one thing you learn very quickly is, if the line goes straight down that is not good ... just to simplify. I know that my statistics professors would be shocked that I'm up here saying that, but you can see that it's very poor. It's a very quick drop, and neither group does well.

The second thing that's a problem is, because these are older adults, in this study -- again, these 3,000 patients -- 52% received intensive therapy -- so, barely half. 11.4% received low-intensity therapy, so these are things like hypomethylating agents, low-dose cytarabine, or similar therapies; and 37% roughly got best supportive care.

So, there is still some reluctance, and ageism unfortunately is alive to some degree…

…in treating older adults with more aggressive therapies. So, we have ... In my mind, we need to really look at physiologic age, and not so much chronologic age, in making those decisions.

So, how do we do this? Well, we say, "Okay, what's the patient's history if they have a new diagnosis of AML?” You want to say, "Have they had one of these prior malignancies? What did we use to treat them? Was it a hematological malignancy? And, have they had any unexplained cytopenias historically?"

Then, "What kinds of therapy did they get? How much of that did they get, and when did they get it? And, do they fit into one of these 2 known categories of prior therapy?"

And then the disease characteristics. Does the patient have myelodysplastic-related cytogenetic abnormalities, or does the pathology report indicate multilineage dysplasia? So, this is part of the process of figuring out, are they in one of these groups?

((Voice Over))
Serious or fatal hemorrhage including CNS hemorrhage have occurred with VYXEOS. Monitor blood counts regularly and provide platelet transfusions as needed.

Due to the risk of cardiotoxicity, VYXEOS is not recommended in patients with impaired cardiac function. Discontinue in patients with impaired cardiac function unless the benefit of treatment outweighs the risk. Calculate the lifetime cumulative anthracycline exposure prior to each cycle of VYXEOS.

Discontinue in patients with severe or life-threatening hypersensitivity reactions, treat the signs and symptoms and monitor until resolution.

Use only if the benefit outweighs the risks in patients with Wilson’s disease or other copper-related metabolic disorders. Discontinue in patients who develop acute copper toxicity.

Administer by the intravenous route only.

Advise females and males of the potential for VYXEOS to cause fetal harm and to use effective contraception.

The most common adverse reactions include hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

IMPORTANT SAFETY INFORMATION

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

Important Safety Information

WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS

VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.