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When Should You Test for AML Mutations?

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Published on May 14, 2020

Key Takeaways

  • The baseline, or when you are newly diagnosed, is the best time to test for mutations.
  • There are currently five different induction therapies that are now the standard of care for different AML subtypes. They are dramatically improving response and survival rates.
  • Relapse is another important time to test for mutations.

In the new world of genetic testing, mutations can be identified to determine a patient's specific acute myeloid leukemia subtype. How does knowing your subtype impact care? And how does having your subtype impact response rates and survival rates?

Watch as Dr. Naval Daver, from The University of Texas MD Anderson Cancer Center, explains how this information is used to personalize AML therapy. 

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Transcript | When Should You Test for AML Mutations?

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Dr. Daver:

What is the ideal time to check or test for mutations? This is an important question in acute myeloid leukemia therapy. We have had a lot of progress over the last two or three years in identifying targeted therapies, and it is very important to look for particular mutations. In my view and at MD Anderson as well as large academic centers across the United States and now the world, the baseline or newly diagnosed time point is probably the most important time to check for mutations. When we say mutations, each institution as well as commercial mutation panels have different numbers. Some will do 50 mutations, 80 mutations, 100, 200, but there are three mutations that I say are most critical, or four. So one of them is FLT3. This is a very common mutation seen in about 30 percent to 35 percent of acute myeloid leukemia. There is a drug approved for the FLT3 mutation called midostaurin (Rydapt) and this can be added to standard induction chemotherapy. It showed improvement in survival when midostaurin was added to standard induction versus doing the standard induction alone, which is what we did before this phase three data showed the midostaurin benefit.

The second mutation that we usually look for is a mutation that is called IDH1, IDH2. Now in a newly diagnosed AML patient, we don't specifically change treatment based on IDH1, IDH2, but there are new drugs called IDH1 IDH inhibitors that have been approved in relapsed AML that may be considered in clinical trials in addition to standard induction and IDH-mutated new AML. So it's good to know or look for these. The third is not really what we call the molecular mutation, but is a chromosome or a cytogenetic abnormality. This is called the core binding factor chromosome changes, and there are specifically two of them; inversion inv(16) chromosome and translocation t(8;21). You don't need to remember those. But the point is if your leukemia, or your patient's leukemia, has one of these chromosome changes, then it is very beneficial to add an immune antibody therapy called gemtuzumab ozogamicin (Mylotarg) to the standard induction, which was shown to dramatically improve the duration of response and survival.

The fourth important chromosome change that we look for is what we call acute promyelocytic leukemia where the chromosome is a translocation t(15;17). This is probably the best success story of all leukemias, maybe all cancers, that we have two drugs, non-chemotherapy, ATRA and arsenic, which can give us 96 percent cure rates or five-year plus remission rates. So these are the four or five groups of patients where we want to know—before we start any treatment—the mutation. Now there's another group, the fifth group, which is also a chromosome based where we look for what we call secondary or therapy-related AML. There are particular chromosomes that the WHO AML classification is listed as being associated with secondary or therapy-related AML. If a patient has one of those and there's another drug called CPX-351 (Vyxeos) that were shown to be superior to the traditional induction.

So now really in the last four years we have entered what we call personalized therapy. We talked about it, wrote about it papers and all for many years. But today truly there are five different potential induction therapies, not on clinical trials, but standard induction approaches that could be used for a given AML based on their molecular chromosome—each of which could dramatically improve both response rates and survival. Some of them could even double or more the survival. So this is the right time to do mutations, and we actually are recommending to wait for those mutation tests. Now you cannot wait indefinitely in AML but seven to eight days in a controlled environment with close monitoring, especially if the patient does not have a very proliferative disease. It is better to know the mutation or chromosome and give them the appropriate therapy than rushing into therapy very quickly.

The second time point which is very important to check for mutation is at the time of relapse. So many of our patients we give them frontline therapy. Unfortunately, they may or may not go to transplant and they may still relapse either before or after transplant. At the time of relapse, there are three mutations that are very important to check for FLT3, IDH1, IDH2. For each of these three there is an approved targeted therapy. For FLT3 there's a drug called gilteritinib (Xospata), a very potent second generation, highly effective, well-tolerated FLT3 inhibitor. That actually showed superior responses, superior survival and better tolerability when it was compared to high dose chemotherapy. All the patients prefer oral, better tolerate therapy, especially if it even gives you better responses and survival.

Same way for IDH1, and there are two drugs; ivosidenib (Tibsovo) for IDH1, enasidenib (Idhifa) for IDH2. All three are U.S. FDA-approved. So if we find one of these mutations, we look for them actually, and if we can find them it is good, because then we can give them these targeted therapies and improve the tolerability, survival and chance for potentially controlling the disease. So these are the two time points where we check for mutations in all of our AML patients.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.
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