DR LOVE: At this point, how do you differentiate the various FLT3 inhibitors that have been studied? You mentioned sorafenib, midostaurin, gilteritinib. I think there are probably others. How do you separate them out at this point?

DR TIBES: So that’s a good question. Sorafenib, it’s kind of a dirty FLT3 inhibitor or not as potent against FLT3, because it inhibits other tyrosine kinases as well. Midostaurin as well, initially it wasn’t allowed as an FLT3 inhibitor, but now it also has FLT3 inhibitory activity.

So midostaurin was used in a randomized Phase III trial which was presented at the ASH meeting, which actually showed an overall survival benefit if midostaurin was added to up-front induction chemotherapy. That was a huge effort, an international study. And that was the first positive study adding an FLT3 inhibitor to induction chemotherapy showing overall survival benefit. It is not approved yet, but definitely the data was positive.

So there are other FLT3 inhibitors. Another one I have been involved with personally, and we presented data in clinical abstracts, is ASP2215, or gilteritinib. That’s also — it was in a Phase I/II study. And that’s public data, so I can talk about it. So we presented it at various meetings, including ASH and ASCO. And we have treated more than 200 patients with that medication as a single agent. And the response rates again, CR/CRI, were in the range of 40% to 50%. And many of the patients actually had maintained responses when they were continued on this medication. Because 1 challenge is achieving a remission, and the other challenge is maintaining a remission.

DR LOVE: In this era where we’re just starting to get single-arm studies, how do you indirectly compare these agents not only in terms of efficacy, but any tolerability differences?

DR TIBES: That’s a good question. I think we cannot really compare different medications and different compounds across studies. That’s why I always highlight the general response rate for those medications. So, for example, for the FLT3 inhibitors, single agent for the first or second generation, sorafenib is a dirty one. Midostaurin is a good one but also a dirty kinase inhibitor, which has shown its overall survival benefit in a Phase III trial. We have quizartinib, or AC220, which also has shown in Phase II studies, and now it’s in Phase III studies, as single agent or in chemotherapy combinations, also our CR/CRI rates, meaning achieving a remission, in the range of 40% to 50%.

The responses in the single agent in the earlier FLT3 inhibitors were often short lived, 6 months, 6 to 9 months. So what we have reported with gilteritinib is that the responses may last a little longer than the first-generation FLT3 inhibitors.

I think another important point to make for every oncologist is, there are 2 mutations in FLT3. One is the FLT3 ITD, which is the internal tandem duplication. And there’s another mutation, the FLT3 TKD, or the tyrosine kinase domain mutation. So the ITD is the more common one. And the TKD, the classic tyrosine kinase domain mutation, is less common. It’s important, because not every FLT3 inhibitor is active against both. So I have seen patients that had both an FLT3 ITD and TKD. And I have seen patients that only had the TKD. For example, sorafenib or quizartinib, they’re not active against the TKD. So it does make a difference to test for both mutations, which most labs do, and then if you have the option of putting the patient on a trial or, at some point, if we have these medications available, distinguishing those 2 FLT3 mutations.

Non-Hodgkin lymphoma (NHL), Hodgkin lymphoma and chronic lymphocytic leukemia (CLL)

Acute and chronic leukemias and myeloproliferative neoplasms

Multiple myeloma (MM)