Hematologic Oncology Update, Issue 1, 2016 (Video Program)Activity of the FLT3 inhibitors midostaurin and sorafenib in acute myeloid leukemia (AML)
3:16 minutes.
TRANSCRIPTION:
DR SMITH: We’re getting really good at picking out these FLT3 mutated leukemias because of their presentation, often monocytic, often high white count leukemias. And they can be pretty abrupt in presentation. We don’t get lots of these people that are lingering for long periods of time. One of the things that’s been really important in the FLT3 world is this idea that there are some mutations of FLT3 that probably have a lot of prognostic importance and others that don’t have as much prognostic importance. And there are low allelic burdens of FLT3 and high allelic burden. And in our program, we decided to add an FLT3 inhibitor. So one of the drugs that’s available, sorafenib, it’s a drug that’s approved for treatment of kidney cancer — has a lot of FLT3 activity. So our clinical trial, in-house clinical trial, is to induce people with ara-C-based chemotherapy, then proceed to give them an FLT3 inhibitor when possible. Interestingly, at ASH this year one of the plenary sessions, a really important session, was really talking about this. Now our study, like the study presented by Rich Stone at ASH this year, added an FLT3 inhibitor to traditional chemotherapy and followed the paradigm that these are high-risk patients. Once in remission, one should consider an allogeneic stem cell transplant as the definitive therapy. And the question really was, what’s the role of additional drugs to block FLT3 in the induction and in the maintenance strategies following a transplant? And for the first time, we saw a really nice study, a large study, randomized trial, Intergroup study, looking at midostaurin, one of the FLT3 inhibitors. That was combined with chemotherapy as well as a maintenance strategy in transplant. And we’re starting to see some benefit in a large study for adding FLT3 inhibitors to traditional chemotherapy as well as following transplant in a maintenance strategy. FLT3 has been this really phenomenally interesting and important target for AML. And that’s because, number 1, we can measure it. Number 2, it offers prognostic implications. And number 3, there’s been a handful of drugs designed really to target it to see if we can improve things. DR LOVE: If someone were to, say, ask you whether it would be rational, reasonable or even you would encourage somebody to actually use sorafenib in the way you’ve used it outside a trial setting, how would you answer? DR SMITH: The answer is, I believe we’re now at the point where patients with high allelic ratio, FLT3/ITD mutations in remission seem to be benefiting from FLT3 inhibition. And when primary docs say, “Hey, my patient lives 4 hours from here. We can’t get her there every month for a supply of drug,” we are able to get insurance companies to help cover the cost because of the effectiveness of it in the clinical trials that show it works. |