Eytan Stein, MD

Videos

Eytan Stein, MD and Hetty Carraway, MD, wrap up their discussion with a review of the unmet needs in AML treatment and exciting therapies in the pipeline.

Unmet Needs and the Future of AML Treatment

Hetty Carraway, MD, explains the importance of bone marrow biopsies in patients with AML receiving treatment with venetoclax + azacitidine.

The Importance of Bone Marrow Biopsies in AML Patients on Venetoclax Treatment

Hetty Carraway, MD and Eytan Stein, MD, discuss the appropriate strategies for the management of cytopenias in patients with AML on venetoclax + azacitidine treatment.

Management of Cytopenia in Patients on Venetoclax + Azacitidine Therapy

Eytan Stein, MD, presents the case of an 81-year-old patient with AML who is unfit for intensive induction therapy for discussion.

Case Presentation: An 81-Year-Old Male with AML

Hetty Carraway, MD, highlights the role of venetoclax + azacitidine in the treatment of patients with acute myeloid leukemia who are unfit for intensive induction therapy.

Treatment of Patients Unfit for Intensive Induction with Venetoclax + Azacitidine

 We also talked about patients with other types of mutations, such as 

 mutations. What’s your approach to this patient population?

 specifically—tend to respond to whatever treatment you give them. They tend to respond quite well to intensive induction chemotherapy. They also tend to respond relatively well to a lower intensity therapy, such as azacitidine or an HMA [hypomethylating agent] and venetoclax. I don’t make my treatment decisions for 

-mutated patients based on the specific mutation. I make those decisions based on what we talked about earlier: the relative fitness and unfitness of the patient. For example, if I had a 45-year-old patient who had an 

 mutation, I’d give them intensive induction chemotherapy. There are no randomized data right now that suggest that adding an IDH inhibitor to intensive induction chemotherapy improves survival.

There’s a phase 1/phase 2 experience that looks very good. But of course, in every phase 1/phase 2 experience, when you combine IDH inhibitors with intensive induction chemotherapy, there are various forms of bias across all those experiences. I’m excited about a randomized placebo-controlled phase 3 study being conducted in Europe by HOVON [Dutch-Belgian Cooperative Trial Group for Hematology-Oncology] and the AMLSG [German-Austrian AML Study Group] that’s randomizing younger patients with 

-mutated AML [acute myeloid leukemia] to receive intensive induction chemotherapy with an IDH2 inhibitor or intensive induction chemotherapy with placebo. I’m hoping that’s going to answer the question regarding whether adding a targeted therapy against 

 mutations to the backbone of 7+3 is beneficial when it comes to survival.

When it comes to initiating intensive chemotherapy while I wait for molecular testing results, whether I do it or not, the only molecular test that’s actionable when it comes to intensive induction chemotherapy is whether the patient has a 

 mutation. The good thing about all the FLT3 inhibitor trials is that the addition of the FLT3 inhibitor to the backbone of 7+3 occurs on day 8 of treatment. That gives you an 8-day window to find out whether the patient has a 

But maybe the bigger issue is that once you find out they have a 

 mutation, you have to get the prior authorization to get them their FLT3 inhibitor and whatever copay assistance you need, and unfortunately that can take time. It can take even 1 to 2 weeks in certain cases. I wait to start intensive induction chemotherapy to the point where I’m sure that if the patient has a 

 mutation, I’ll have their FLT3 inhibitor on hand on day 8 so they can start treatment. If I know I’m going to have that result and have the medication on hand by day 8, I don’t have a problem starting treatment a little earlier when it comes to intensive induction chemotherapy.

 I completely echo your comments about patients with 

 mutations and starting a FLT3 inhibitor on day 8. We’re sometimes challenged by our patients with core binding factor leukemia, the inversion 16 and translocation (8;21) and the addition of GO [gemtuzumab ozogamicin] to the backbone of induction chemotherapy. The 2 cases that we’re challenged by in terms of doing the induction therapy and adding to the backbone is both the FLT3 inhibitor, which we typically don’t have a problem with, and the favorable risk with GO. Are you challenged by that at all? What’s your timeline like in New York?

 It’s an interesting question because for a variety of reasons that are probably too complicated to get into right now, we have been a non-GO institution. We never give it. That’s a discussion over a drink in a bar about why we don’t give it.

 You might imagine it would be challenging if you did give it to patients in terms of the turnaround time.

 Of course. We get our FISH [fluorescence in situ hybridization] results back relatively quickly, but it certainly is challenging. If you were a place where you gave GO, especially because there seems to be a benefit, I’d want to wait for those FISH results. This is a little off topic, but a lot of these results from a technical standpoint can be done quickly. At large institutions, or if you’re sending it out to an external vendor, the issue often has to do with the resourcing that’s available to have the personnel turn these things around. I’m hoping one day we’re able to turn these things around quicker than we currently do.

 I’ll echo that, but we handle this by relying on our pathologists at our institution. If our pathologists are looking at the morphology and they’re worried about a core binding factor leukemia in morphology alone, we give it. We don’t wait for the FISH tests. We’ve learned that we haven’t missed that many, based on relying on and communicating with our pathology experts.

 Sometimes you don’t need all the fancy testing.

Eytan Stein, MD, continues the discussion of AML treatments with a look at the options for patients with AML and mutations.

Eytan Stein, MD | Authors

Articles

Unmet Needs and the Future of AML Treatment

The Importance of Bone Marrow Biopsies in AML Patients on Venetoclax Treatment

Management of Cytopenia in Patients on Venetoclax + Azacitidine Therapy

Case Presentation: An 81-Year-Old Male with AML

Treatment of Patients Unfit for Intensive Induction with Venetoclax + Azacitidine

Treatment Options for AML Patients with IDH2, RUNX1, or DNMT3A Mutations