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IACH Focus on Leukemia 2020 | The need for new treatment regimens in older AML patients

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Farhad Ravandi

Farhad Ravandi, MD, University of Texas MD Anderson Cancer Center, Houston, TX, discusses problems treating older patients with acute myeloid leukemia (AML). The majority of AML patients are over 60 years old. For many decades, the only treatment strategy for AML included the use of cytarabine, anthracycline and idarubicin. However, as patients get older, they are less able to tolerate chemotherapy and therefore that regimen has been associated with high toxicity, morbidity and mortality. Therefore, there is a need to develop a new treatment regimen that is low in toxicity but still as clinically effective. Additionally, Dr Ravandi discusses the combination of hypomethylating agents, such as azacitidine and decitabine, with venetoclax. This interview took place during the 2020 Annual Meeting of the International Academy for Clinical Hematology (IACH).

Transcript (edited for clarity)

For the majority of patients with AML are older and the vast majority are above the age of 60 and 65. So, for many decades now we have had only one strategy in treating any AML and that was a combination of cytarabine and an Anthracycline, either daunorubicin or either idarubicin. We have used that in our older patients as well and this is across the board in U.S. and Europe. They typically have used this 3+7 regimen, but unfortunately, as we get older, our ability to tolerate chemotherapy gets less and giving that kind of regimen to older patients has been associated with significant toxicity and morbidity and mortality...

For the majority of patients with AML are older and the vast majority are above the age of 60 and 65. So, for many decades now we have had only one strategy in treating any AML and that was a combination of cytarabine and an Anthracycline, either daunorubicin or either idarubicin. We have used that in our older patients as well and this is across the board in U.S. and Europe. They typically have used this 3+7 regimen, but unfortunately, as we get older, our ability to tolerate chemotherapy gets less and giving that kind of regimen to older patients has been associated with significant toxicity and morbidity and mortality. So our department in particular and other groups have been interested in developing less toxic and yet, as effective regimens for older patients. Of course, the biggest problem are the very old, over the age of 75 and with significant comorbidities and for those we’ve been using essentially single-agent hypomethylating agents over the last two decades.

This is not the best option, because single-agent hypomethylating agents, like azacitidine or decitabine are only associated with about 20 to 30% response rate. They’re much better tolerated, but you know, of course, you want to have a regimen that is well tolerated, but also is highly effective. Now with the introduction of venetoclax we are getting there. So the combination of azacitidine and venetoclax has clearly been shown to be superior to single-agent azacitidine. We’ve also done strategies combining decitabine plus venetoclax, and this has become the standard of care for what they call older and unfit AML at the moment. And the question is, can this be expanded to more fit and younger AML patients? And I think that will be the question of the future.

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