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Transcript

((Voice Over))
Welcome to the presentation titled “t-AML: 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 Tuscon, Arizona. She will take you through an overview of t-AML, or therapy-related acute myeloid leukemia.

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

Here is that new World Health Organization Classification Terminology. If any of you have had an opportunity to look at the World Health Organization…

…Classification of Hematological Malignancies, it reads a bit like a chemistry textbook. So, everything is getting very complicated, very molecularly driven, and each individual subtype of disease is categorized by cytogenetic profiles and molecular attributes. So, it's become a ... And this is, I think, true of any of the malignancies that we're dealing with today. So, we just have to sort of embrace that…

…hold on tight, try to learn as much as you can, so it's good to be here. But this is the way it's going to be going forward as we get more and more into individualizing therapy based on risk stratification and the disease profile itself.

So I've been at the Arizona Cancer Center for 33 years, and I've followed some patients for more than 20 years as a nurse practitioner. And we're beginning to see more and more…

…secondary malignancies from prior therapies. And we know that there are 2 clusters of patients: one group receiving alkylators and radiotherapy, particularly to the pelvis…

…so we even see this happening in patients with prior radiation for prostate cancer because you're radiating the marrow -- the primary source of marrow, which is in the pelvis.

Drugs in this category -- think about these drugs. Cytoxan, cyclophosphamide, carbo[platin], cisplat[in]; mechlorethamine, we don't use anymore, nitrogen mustard -- we used to use that in primarily Hodgkin patients way back when; procarbazine, similarly; chlorambucil, still around; melphalan -- well, what do we transplant people with myeloma ... high-dose melphalan; carmustine; and busulfan.

And so, exposure to these alkylators…

…can put people at risk for secondary malignancy, treatment-related AML in particular, 5 to 10 years out from their diagnosis. We're starting to see…

…women with breast cancer who've had AC develop…

… treatment-related AML. It's a very devastating diagnosis ... and we'll talk a little bit about the prognosis here in a minute.

The second group are Topo-II inhibitors [topoisomerase II], and these induce chromosomal translocation. So, we'll look a little bit about…

…these balanced and imbalanced chromosomal abnormalities, and kind of looking at where are those coming from relative to someone's treatment history.

But drugs that we see here are VP-16, or etoposide; teniposide…

mitoxantrone; epirubicin; and doxorubicin. So, you think about anybody getting…

…CHOP chemotherapy, anybody getting AC; anybody getting Cytoxan as a part of whatever regimen; high-dose melphalan...

…these are things we use commonly, and it is something that when we have conversations with people getting these primary therapies…

…we have to talk about potential for these treatment-related secondary diagnoses.

You can see that the onset…

…here is much quicker, so in people that get some of both groups there is some variability in there, but that group you tend to see a peak of 2 to 3 years.

The overall percentage of patients with AML with this treatment-related subtype is 5 to 10 percent, so not the largest group.

So, let's just talk about a hypothetical case here. So, characteristics of treatment-related AML.

So, this is a woman with a prior history of radiation and chemotherapy; this could be for breast cancer, lymphoma, multiple myeloma, ALL even; 5 to 10 years after exposure to these agents; and 2 to 3 years after exposure to topo-II inhibitors is the potential risk.

So, this is important when we're seeing patients who are coming in to have their follow-ups…

…and when you start saying, you know, you're going to release patients after their 5-year anniversary. We don't typically do that unless we know there's somebody who's going to be keeping an eye on their counts…

…because typically what you start to see is the development of cytopenias, and if they have a history of hematological malignancy you're going to think…

…"Well, maybe that malignancy is back," but in fact it may be that it's one of these secondary problems.

So, you basically are going to start to see the development of cytopenias.

There's a high incidence of these abnormalities and overall survival is less than a year.

So, these people have a very poor prognosis in the absence of effective treatment.

Here are some of the different groups that are involved, and this is based on a study of over 3,000 patients from 2000 to 2013 in Denmark -

6.6% of whom had the treatment-related AML.

Solid cancer ... so, we're starting to see patients with colorectal cancers who are getting treated with new combinations of drugs. We've had breast, obviously; ovarian cancers -- you think about the platinums being in that mix. So, we're seeing a lot of patients now that ovarian cancer patients are living a lot longer where they're ending up with these treatment-related AMLs.

Lymphoproliferative disorders ... obviously, these people are at high risk, so you look at lymphomas, myelomas as well.

Rheumatic diseases ... so, these are people that may be on methotrexate for years, and are developing actually treatment-related AML.

And then ALL, which in men…

…we treat for 3 years minimum, and in women they get treated for a full 2 years. So, they're exposed to multiple combinations of drugs over a long period of time.

((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.