Deciding a Frontline Treatment for Newly Diagnosed AML

Transcript: Naval G. Daver, MD: The most difficult challenges in managing patients with acute myeloid leukemia are identification of appropriate prognostic and targeted markers that can be quickly available so we can use targeted immune therapies in an appropriate way. We now have a number of drugs that are showing great efficacy such as the FLT3 inhibitors, including midostaurin, gilteritinib, and quizartinib, as well as IDH inhibitors and new monoclonal bispecific antibodies. But the key is to select the patients who will have the maximum benefit for these treatments, and that requires rapid molecular sequencing data, access to these drugs in a quick approach, as well as doing combination therapies, which are showing much better activity than single-agent approaches. So a lot of these things are moving, but we see there’s a big difference between the large academic centers that have been involved in the trials where sequencing and immune results come in within 2 to 3 days versus community hospitals, or even smaller private practices where it may take 8 to 10 days, and then often the patients miss the opportunity to get these effective targeted immune therapies.

The biggest way patient factors influence decision making is differentiating between what we call high intensity therapies, and lower intensity therapies. Historically we used to use high intensity therapies very frequently because the response rates with high intensity regimens such as 3+7 [daunoribicin/cytarabine], or FLAG-IDA [fludarabine/cytarabine/G-CSF/idarubicin] are much higher than it used to be with the historical low intensity therapies like azacitidine, low dose cytarabine. We would see response rates of 70% to 80% with high-dose chemotherapy versus 20% to 30% with low dose therapy. And so people would be much more inclined to do high intensity therapy unless the patient really was above 75 years old or a very poor candidate for other comorbidities.

Now the gap has actually become much smaller. What we call lower intensity therapies, such as azacitidine with venetoclax, or low-dose cytarabine with venetoclax, or hypomethylating agents in combination with some of the FLT3 inhibitors, are actually showing response rates in the range of 60% to 70%. So almost as good, or maybe even as good as we would get with high intensity therapy.

Now we don’t have enough durable follow-up and survival endpoints, but it is becoming a much more intricate process. And patients are now involved where we may have a 70-year-old, or a 65-year-old who could be a candidate for intensive chemotherapy, but with a lot of risks, a lot of toxicities, long stay in the hospital, high early mortality of 15% to 20%. And that same patient may be able to get azacitidine/venetoclax, or other low-dose therapies with an equivalent response rate, maybe with a similar survival, with a lower early mortality, less days in the hospital, less toxicity.

So we are now presenting these options to our patients saying that these are newer, we don’t have as long follow-up, but these are probably good considerations. And then patient will say, “No, I want to try it and test the thing, the one that has the best rack record, transplant; I want to go for the cure. I don’t mind managing toxicities. If I have to be admitted, that’s OK, that’s my end goal.” And many will say, “No, if you can get me a few years, if you think it has a high response rate, I can spend more time outside the hospital with my family, with friends; that’s what I want.” We actually do see that there’s not one answer. Patients have very different goals of what they expect and want, even patients who are 65, 70 years of age.

Transcript Edited for Clarity