Ryan Haumschild, PharmD, MS, MBA: I know there's been a lot of changes in AML [acute myeloid leukemia] therapy and even with the different agents that are being preferred as frontline therapy. Dr. McCoy, can you talk about some of the recent changes you've seen in AML, specifically some of those first-line treatments?

Cole McCoy, MD: Dr. McCloskey really laid out that patient workup, gathering specific information regarding cytogenetics and molecular abnormalities that not only gives a prognostic value but leads to leads to specific treatments. There's been several new FDA approvals in the last 5 years, and I’ll list some. We had our FLT3 inhibitor, midostaurin, which was in 2017; gilteritinib followed in 2018. We had enasidenib, which is an IDH2 inhibitor, in 2017, which followed by the IDH1 ivosidenib. Then, we have venetoclax, the BCL2 inhibitor, in 2018, as well as glasdegib, which affects the hedgehog pathway. Those are all targeted therapies that infiltrated the treatment algorithm, some of them upfront and some in their relapsed/refractory setting. There's other non-targeted agents that hit the market as well, or came back to the market like gemtuzumab ozogamicin, which is an antibody drug-conjugate to CD33 and was actually pulled off the market due to hepatotoxicity but then came back on the market. There was a new formulation called liposomal daunorubicin cytarabine, CPX-351, which was in 2017. As we can see, just in the last 5 years, there has been several new medications in our arsenal for treatment.

Going back to your question for first-line treatment, when breaking those up into 2 buckets for induction-eligible patients, not everyone will see receive what they did in the past. There was a traditional 7 plus 3, so there were 7 days of continuous cytarabine and then 3 days of an anthracycline; that could be daunorubicin or idarubicin. Now it's changed; there's more information that we have to gather, so let's say a patient’s cytogenetics came back with core binding factor AML, which is t(8;21) translocation or inversion 16. We would give the 7 plus 3, but we would add that gemtuzumab ozogamicin to that treatment. Another example would be looking at poor risk cytogenetics, like a secondary AML. They either had an antecedent MDS [myelodysplastic syndrome], or they receive that liposomal daunorubicin cytarabine instead if they're older. That changed the landscape. Another one of the targeted agents that we use upfront: if the patients have flipped 3 mutations, we'll give that 7 and 3, and then we'll add that midostaurin, which is an oral chemotherapy, on days 8–21. There's a lot more information we gather upfront, not only for prognostic value, but it really does affect our treatments.

Looking at the flip side for those patients that are not induction eligible—older patients—one of the biggest changes that we've seen is the BIOLASE study, which was the approval of venetoclax. These patients historically had poor prognoses and not many treatment options out there, but with azacitidine venetoclax, they do quite well. They're improved from an overall survival of 14.7 months vs 6.9 months and have a complete remission rate of 36% vs 17%. In that older patient population with comorbidities, we have a much better treatment strategy.

Ryan Haumschild, PharmD, MS, MBA: You laid out a lot of updates there, which I think are exciting and add to that breadth of treatment options for patients. The more we become specific, being driven by the specific cytogenetics, the better outcomes we can have. I always get excited when I hear about overall survival being increased. That’s the gold standard of what we're looking at in terms of treatment. With all those changes you mentioned, are there any other NCCN guideline changes that you've seen specifically for AML outside of front line that you want to mention, anything else that you think is relevant in the disease state?

Cole McCoy, MD: I know I threw a lot of different treatments out there, but to goi back to all those different treatments that were approved and focusing on the upfront… We talked about midostaurin for a specific FLT3 mutation, [the return] of the gemtuzumab ozogamicin for more favorable risk or core binding factor AML. Patients that have poor risk within that secondary AML could potentially see that liposomal daunorubicin cytarabine. Those all have changed, but it has a lot of NCCN updates, and it's affected the relapse/refractory as well. I mentioned a couple of drugs earlier, ivosidenib and enasidenib. The IDH1 and the IDH2 mutations, respectively, were first approved in the relapsed/refractory setting. We have oral medications now that we treat patients with that can be treated from home in the refractory setting. The other FLT3 inhibitor, gilteritinib, is approved in the relapsed/refractory setting as well, another old drug that you can use from home. I know they're being studied in other realms, but that's the main NCCN approvals as of now.

Ryan Haumschild, PharmD, MS, MBA: To see the different agents come up adds a lot of value. We look at orals, and we think about adherence. How do we make sure that the patient stayed here on the therapy? We might see that great clinical efficacy in the clinical trial, but does that translate to real-world evidence? Is that patient staying motivated? As we finish up talking about NCCN guidelines, Dr. McCloskey, is there anything else that you want to add around the treatments? Some of the biggest changes you've seen since you've been practicing for a while now in this area?

James McCloskey, MD: There have been a lot of changes. One thing to highlight since it's changing so quickly are some of the things that have stayed the same. One thing that I think is important is that for fit patients, induction therapy is still standard. It is still important that patients are evaluated for their eligibility for intensive chemotherapy. Likewise, it's important that all patients under the age of 65 or 70, at the very least, be evaluated for stem cell transplant. As someone who works in an urban area, we've built a lot of really rewarding and valuable relationships with the community where we collaborate a lot on patients’ care. It’s still important that we have those patients assessed and get them plugged in with a transplant center, as well as offer patients [induction therapy for those] who are eligible for induction.

Ryan Haumschild, PharmD, MS, MBA: I love that you brought in those community and academic relationships because I think it's so important for AML patients. We're seeing so many more patients getting access to therapy early or getting access in their own community. Establishing those relationships not only for treatment, but bone marrow transplant, is the right way to establish patient-centered care.

This transcript has been edited for clarity.