Treatment options for newly diagnosed AML


Courtney DiNardo, MD: Hello everyone. I’m Courtney DiNardo at [The University of Texas] MD Anderson [Cancer Center] in Houston, Texas. Today I am going to talk about the use of venetoclax in the treatment of newly diagnosed acute myeloid leukemia [AML].

Treatment has changed so much in terms of the opportunities and treatments available to our patients. There is an age limit of 60, which is very arbitrary, so I encourage you not to think of it as a point of discrimination but to assess your patient’s fitness and the suitability of a chemotherapy regimen intensive or non-intensive chemotherapy. Patients who are appropriate for an intensive chemotherapy regimen are usually younger patients who have no underlying comorbidities.

There’s what we call standard 7+3 therapy, which is 7 days of cytarabine and 3 days of anthracycline. We also have CPX-351 approval, called Vyxeos. This is for patients who have treatment-related AML or AML of an underlying secondary malignancy, whether solid or different hematological malignancy. They then develop AML or AML with MDS [myelodysplastic syndrome]–related changes. For our patients eligible for intensive chemotherapy who are FLT3 mutated, the standard is intensive chemotherapy with an FLT3 inhibitor. Midostaurin is the recommendation for these patients.

For patients who were older or unsuitable for intensive chemotherapy due to underlying comorbidities or things like that, the standard was a hypomethylating agent alone: ​​azacytidine or decitabine mostly in the US, or a low-dose cytarabine, which is 1 of the older standards and used worldwide, but not often in the United States. Over the past few years, we have gained approval for several combinations that have improved outcomes for seniors. They receive low-intensity combinations: azacytidine with venetoclax, decitabine, a hypomethylating agent with venetoclax, and low-dose cytarabine with glastegib or venetoclax. We don’t use many low dose cytarabine regimens in the US, but these are approved and available. A recent approval just obtained in May: azacytidine with the IDH1 inhibitor ivosidenib for newly diagnosed patients HDI1-LMA mutated.

Fitness is a difficult thing to discuss in one sentence because we still don’t have a single approach to say who is fit for intensive chemotherapy. We look at patient age because age is associated with frailty and other comorbidities. In general, people over the age of 70 or 75 are not suitable for a standard intensive chemotherapy regimen. For patients 70 years and older, the risk of toxicity from intensive chemotherapy is a challenge; the risks outweigh the benefits. But for younger patients who have underlying comorbidities, especially cardiac or pulmonary comorbidities, or who have a poor performance status, i.e. they are not lifted more than half of their day, these things are associated with a higher risk of toxicity, morbidity, and mortality than standard intensive chemotherapy. The FDA uses the Ferrara criteria to determine suitability. They include things that I’ve talked about: age over 75, underlying heart dysfunction, underlying lung dysfunction, poor performance status, or something else that puts the patient at risk for standard intensive chemotherapy, such as inflammatory bowel disease.

Transcript edited for clarity.


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