What is lymphodepleting chemotherapy?

What is lympho-depleting chemotherapy? Lympho-depletion chemotherapy, it's exactly that. So what does lympho-depletion mean? So we all have immune cells, T cells, NK cells, all these things in our body, that if even though the CAR T is from your own T cells, that molecule, that genetic modification that we do is not from your body. Your own T cells are smart enough to find it, just like they find viruses and other immune infections. When we give you those, if we didn't do lympho-depletion chemo, what would happen is we give those cells, your immune system kills them off. So they don't even get a chance to find the myeloma because your immune system is going to say, this isn't supposed to be here. So lympho-depletion actually knocks down those lymphocytes. So like I said, your T cells and K cells, B cells, so that your immune system is lower. And then when we give the CAR T cells, they can actually make it to the myeloma, do what they need to do. They start growing. And then in a week or so, that lympho-depletion chemo stops working, your immune system comes back, and then it does start taking out some of those CAR T cells, which is what we want. We don't want those CAR T cells at the highest level being there all the time. After they've done what they've done, we'd like for most of them to go away. What is usually used? Is it an inpatient or outpatient administration? How long is it given? So lympho-depletion chemo for the most part is two drugs right now, cyclophosphamide and fluderabine. And those are the ones that really we know knock down your T cells well enough and long enough. And that's why I said we don't like to use Cytoxan or Vendimustine prior to apheresis because we know it kills your T cells, right? So that's the main reason. So now we do want to kill them. We want them to be knocked down. So we use Cytoxan and fluderabine usually for three days. But most patients will get it outpatient because this is just chemo, but it's every day for three days. And if my patients are really sick or they might have some kidney issues, then maybe we do it inpatient. But for most it's outpatient. And then you get two days of rest for the most part. So after you get those three days of chemo, usually there's a two day rest period and then you get the T cells usually in the hospital. We're all trying to figure out how to do it all outpatient. But right now, just to make sure patients are okay, we usually do that part in the hospital so people get admitted in between the lympho depletion and the cells. Lympho depletion chemo usually is a few hours long. The main part is they check your blood counts, make sure you're okay. It depends on the institution. We tend to give fluids before, possibly even after, just to make sure patients' kidneys and everything else gets flushed out. Very few patients will get something called mezna. Most patients don't. But if you've had a lot of cytoxan, it can cause bladder irritation. So if someone's on mezna, then it's a 24 hour pump that we do. But again, most patients don't need that. It's just a couple of my patients were surprised that they needed that. So I like to make sure everyone knows everything. But again, it's usually just a few hours and then you're done. And then you come back the next day and it should be the same for all three days. The main part is the forgiving pre and post normal saline. Or if someone's kidneys are a little bit on the borderline. Or if I'm not giving any fluids, then it turns it into just a couple of hours. So lympho depletion chemo, again, it's in the same category as melphalan. So if anybody that has stem cell transplant, they think, oh my gosh, it's chemotherapy. It's at a much lower dose. So compared to transplant, most patients do really well with this. But the major side effects are usually nausea. We give nausea anti-emetics before, the anti-nausea medicine before the doses. But we also make sure our patients have some just in case and fatigue. So usually by that third day, some patients will have some fatigue. And again, with the fluid, I do have some patients that will get a little bit of fluid overload or a little bit of fluid in their ankles or legs that we just sort of monitor and it goes away after a couple of days. But those are the main side effects. Again, we'll see the platelets come down. We'll see the white count come down. But those are things we know are going to happen, and especially the white count. Very rarely have I ever needed to transfuse someone with just lympho depletion chemo. Most people do not lose their hair, but these drugs in general can cause thinning. So I've had one patient lose a lot of her hair before. But most patients, it's just thinning. And that's it. Thank you. Thank you. Thank you. Thank you.