What is bridging therapy?

What is bridging therapy? So bridging therapy is something that not everybody needs, but when patients first get their CAR T cells collected, so this is autologous CAR T's that we're talking about, we have to collect those cells by apheresis, and then it takes four to five weeks sometimes to have them made and grown and come back to us, down to the hospital. So in that meantime, we have to make sure that myeloma is staying controlled. And basically, some patients, their myeloma is okay and stable, so we might not need any bridging therapy. But sometimes, if patients have a disease that's really rapidly growing, we don't want them to have kidney problems or problems with their counts right before there's a need to get their cells. So we give treatments that are myeloma specific to help control that disease or maybe even knock it down a little bit so that the CAR T cells have a better chance of killing all the myeloma. There's no standard of care for bridging chemotherapy. So for most patients, we do whatever we think is going to work. So a lot of patients, whatever therapy they were on before, if their disease is just slowly increasing, we might keep it on so that it doesn't take off. Or we might change a couple of drugs that they've had in the past that worked. Sometimes we'll use something newer just to make sure we have a good control. But the main thing is we don't want, right now, we don't know the answer, but we don't want all the myeloma to go away because we don't know if the CAR T cells will work then, if there's no myeloma there for them to attack. And the other, again, is we don't want a lot of myeloma because that's where people end up getting more toxicity. So in the patients with silted cell that we've talked about before, there's a group of patients that get this neurotoxicity. It's a small number of patients. It was 9% who got really bad neuropathy and things like Parkinsonianism. And what they found was it was the patients that had a lot of disease going into CAR T that were more likely to get it. So in the rest of their studies, they actually made sure with bridging therapy the disease was controlled and then they didn't see those types of toxicities. So again, that's the main goal of bridging. Are there any bridging therapies that should be avoided? We don't know what to give yet. I will say we don't know if there's anything we should avoid for bridging. Before apheresis, so before you actually collect your cells, we want your T cells to be the best possible. And so there are certain drugs we tend to not use, like alkylators. So bendimustine, cyclophosphamide, those are the ones that knock your T cells down a lot. So we don't want to use that right before the collection or the apheresis piece. For bridging, I use Cytoxan all the time. If someone's disease is really taking off and I need something strong to work, I will use that as long as it doesn't affect their counts. So any treatment we use, we want to make sure that by the time that four to five week period, their counts are going to be okay, their kidneys are okay, they're not having major toxicity. The other one is the BCMA therapies. So we don't know the answer yet, but you know, some people will say let's avoid all BCMA. So the ADCs or you know, we don't have a bispecific right now that we can just use off the shelf. So that's not a problem. We have the ADC. To use it during bridging, the question is, will it knock down that BCMA expression so that when the CAR-Ts go in, they can't find the myeloma as well? There's no evidence of that, but we just don't know. So we're sort of trying to figure that piece out. But if someone's disease is really bad and I need something to knock it down, I will use the ADC to help knock it down before they get to CAR-Ts.