What are the common side effects of ivosidenib and how are these side effects managed?

What are the common side effects of IvoCitinib? How are they managed? So the common side effects of IvoCitinib are really, it's actually very well tolerated. Now, the main side effect that we really worry about with IvoCitinib is a special toxicity called differentiation syndrome. And it has to do with how IvoCitinib works to treat leukemia by making these very early type leukemia cells grow up quickly into mature blood cells. And in that process, it can cause things like fever, fluid accumulation, and problems breathing. And so we monitor patients very closely for this differentiation syndrome. And if it does occur, we promptly institute medications called steroids to help treat that disease. But it is, in general, a pretty well tolerated medication, and it's not associated with a lot of lowering of blood counts that we see with other leukemia-directed treatments. Can IvoCitinib cure AML? IvoCitinib is a great medication that can produce responses in patients who have IDH1-mutated AML. But unfortunately, it's not a cure for AML. And that even if you treat someone and they do get a response with IvoCitinib either alone or with combination with another medication, the leukemia can come back over time. So unfortunately, it's not a cure. How effective is IvoCitinib for IDH1-positive patients? IvoCitinib is very effective for the treatment of IDH1-mutated acute myeloid leukemia. And we measure effectiveness in a few different ways. And one way is a response. Does the leukemia go away when we look under it under the microscope? That occurs in approximately 40% of patients who are treated with just IvoCitinib alone. And if you add IvoCitinib with combination with azacytidine, that number goes up even more to 50%, 60% of patients. But the other way that we really measure how effective a medication like IvoCitinib is is how much it really improves someone's lifespan, their survival. And the combination of azacytidine and IvoCitinib significantly improves a lot of these things and these outcomes versus just azacytidine alone. Importantly, too, IvoCitinib can also help clear that mutation, that IDH1 mutation. It can make that IDH1 mutation go away. In patients who respond, especially about 20-30% of patients with a single agent and even more when given a combination with azacytidine. It's so good at targeting that mutation and specifically targeting that part of leukemia that has that mutation. It's so good at making those cells not be leukemic anymore that it makes that mutation go away. While research is being done to make IvoCitinib even more effective. Research in IvoCitinib is taking place in a number of different ways. One way we've touched upon is how to make IvoCitinib even more effective in IDH1 mutated patients. And that includes combining it with drugs like we mentioned azacytidine before, but also other medications such as Venetoclax and trying to see if instead of two drugs, three drugs is even better in terms of producing responses and improving survival. Other ways we're trying to improve IvoCitinib in the treatment of IDH1 mutated AML is trying to understand which patients will respond and which patients won't respond. So we can predict if you give someone with IDH1 mutated AML IvoCitinib, is this someone who's going to have a good outcome with it or is this someone who's not going to respond? And the last way we're really looking at to improve IvoCitinib treatment is to understand how patients become resistant to IvoCitinib. How do patients relapse? What are the mechanisms and what are the ways that the leukemia cells can figure out a way around IvoCitinib and continue growing? And identifying those mechanisms is really important so that we can develop strategies to target those mechanisms so patients can enjoy longer responses and have a longer life while being treated with IvoCitinib. How else is IvoCitinib being used? I think a really important key about IvoCitinib is that it has become approved now in the context of other leukemia drugs being approved, namely Venetoclax. So oftentimes an oncologist will have the decision in someone who's IDH1 mutated whether to treat them with Azacytidine Venetoclax or Azacytidine and IvoCitinib. And that's a distinction and a decision that is very hard to make because they're both very effective regimens. There is some people who want to give Azacytidine and IvoCitinib because it is better tolerated and easier to take than Azacytidine and Venetoclax. While other people are of the mindset that it's better to save IvoCitinib later on in the disease course so you can treat someone who maybe relapsed after Azacytidine and Venetoclax. And so I think it's important for patients to really discuss the distinctions between those two and to make the best decision for them whether it means going for something that may be potentially better tolerated versus something that is potentially worse tolerated but then saving treatment options for later on in the disease course. A lot of the decisions have to do with risk category and about how aggressive their leukemia is. H1 mutations often coexist with other mutations which can influence how high risk and adverse risk someone's leukemia is. But a large percentage of the discussions have to go down, have to deal with safety and tolerability and does the side effect profile of IvoCitinib or Venetoclax, is that better for that patient? So for instance, Venetoclax can cause low blood counts often requiring transfusions and that can be very burdensome for some patients while in other patients that might not be as big of an issue. IvoCitinib and Azacytidine has this risk of differentiation syndrome and some patients are really nervous about that. So it's important to have a dialogue with your oncologist about these different side effects and also about the comparing the efficacy and the treatment effectiveness of the two agents to see which one is a better choice for every individual patient.