What are the common side effects of venetoclax?

What are the common side effects of venetoclax? So there are two well-known side effects of venetoclax. So one is something called the tumalizer syndrome. So that was first seen in a different disease called CLL, chronic lymphocytic leukemia. So while I'm not talking about that, venetoclax has been approved for CLL a while ago before AML. And CLL cells are truly dependent on Bcl2. So you hit them with a little bit of venetoclax and they're going to die. So what happened in the CLL patients because they have a large tumor mass, usually with the lymph nodes and high white count. That's kind of typical presentation. When they took venetoclax in the initial studies, there was so much tumalizer. So there was so much tumor killing at the same time, very short time. So the drug works very quick. So within hours, essentially, that there was this complication called tumalizer syndrome. So what happens is essentially when the cells burst open, they release a lot of substances. One of them is being potassium. And when the potassium levels are high, that can impair cardiac function and cause arrhythmias. And this could be lethal. So this became what we call black box warning for venetoclax. And the initial studies, in fact, in CLL were held for some time till we figured out how to give it safely. So again, it's different than acute myeloid leukemia, but it can still happen in acute myeloid leukemia. So to mitigate that, we limit the starting white blood cell count to less than 25. And we have drugs to reduce that. And then when we start venetoclax, we usually monitor the labs very carefully, like twice a day for the first few days, just to make sure that we don't have the complication. It's easily treatable when you can recognize it. But the main thing is just to kind of see that it's happening. In AML, it happens very rarely. It's only about 4% risk of TLS, which is mainly like laboratory and not a clinically significant risk. But still, these guidelines of monitoring and starting with a low white count exist. The second more common side effect that I already mentioned, that's something that we're trying to educate all the physicians across the U.S., is what we call myelosuppression. So the patients develop low counts for a long time, especially when you use it uninterrupted. So it's again, the label tells you to use it 28 days a month. And so what happens is that many physicians would just keep going with this treatment. It's oral medication. So you just give the chemotherapy like we give some other medications on a continuous basis. And then the counts have a very long time to recover, and patients usually develop infections. So that's on target side effect, because again, normal myeloid cells depend on BCO2. And again, the ways to mitigate that is to interrupt treatment when the counts, you know, when you treat, for example, for two or three weeks, you interrupt treatment and allow counts to recover. And if the count recovery takes too long, despite this interruption, in the next cycle, you interrupt it for after two weeks of treatment. So essentially, we have to adjust the duration. Once patients are in remission, we have to adjust the duration of treatment based on their count recovery, based on the ability of the normal bomber to recover from this toxicity. And that requires a little bit of practice and a lot of education to make sure that we're doing this safe across the country. How are side effects typically managed? So the side effects, again, there are two side effects. So one is the Stumulizer Syndrome. So if potassium is high, we have special medications to bring it down. We have to repeat labs a few hours later. It's not just potassium. So sometimes something called uric acid is being elevated. And that's something we see when in general there's a lot of leukemia in the blood. And we use prophylactically agents that reduce uric acid regardless of even therapy. So there are certain measurements. Then patients usually have to drink a lot of fluids to kind of wash out everything, the debris. So this is our management of Stumulizer. Also, phosphorus is another one that is easily managed. For the mild suppression, I already talked about. So it's basically interruption of the duration of the nanoclux management. But these are pretty much the only side effects. Again, we do not see any side effects related to the kidney, liver function, cardiac side effects. So essentially the only side of, you know, clinically significant side effects is the risk of infection because of the low counts that develop with prolonged therapy. And then we also use growth factors sometimes. So when the counts are low and they do not recover in time, we do use generously the growth factors to help the recovery if patients are in remission. So that's another approach to manage the mild suppression. What are growth factors? There is a growth factor called granulocyte stimulating growth factor. It's called GCSF. It has many different names depending on the company. But it's essentially an injection under the skin. And you can give one or two or three injections like every day. And that facilitates a wide count recovery. It's used routinely, for example, in patients who are undergoing stem cell transplantation to facilitate engraftment of the stem cells. So it's approved for the chemotherapy induced low counts, wide count particularly.