Is CAR-T a one time treatment?

Is CAR-T one time treatment?

Typically, CAR-T cell therapy is a one off treatment and most of the trials that have been performed so far give CAR-T cell therapy as a single infusion. Now, within myeloma, unfortunately, we are seeing that patients do relapse following CAR-T cell therapy, which is then asking the question, can you re infuse patients? So far, we don't have much data. The little data that we have is that repeat infusion with exactly the same CAR-T cell has not been very effective. 
So I think if you are going to have a second CAR-T cell infusion, you may need to think about switching the antigen or adopting a slightly different approach to make it more effective. What we are also, however, looking at is to give maintenance treatment following CAR-T cell infusion to try and really extend that progression free survival and in multiple myeloma, try and get that cure that we're desperate to achieve. 
So far, we really don't have any data about giving any maintenance treatment after CAR-T cell therapy. But it does make sense to give some of the immunomodulatory drugs. This may include daratumumab or lenalidomide, which are standard drugs that we give for myeloma, but they modulate the immune system to try and enhance those effects of those CAR-T cells. 
So those clinical trials are being planned, and we'll have to wait to see what some of those results are like. 
So I think that's a that's an excellent question when we don't fully have the answer to yet. Right now it is. Right now it's a one time treatment. Patients have their cells engineered in the lab and then they receive a short course of lymphoma bleeding chemotherapy to kind of prepare their body and bone marrow. The immune system for the CAR-T cells. 
And they get that as a one time infusion. And then we just watch after that. I think one of the areas of sort of development going forward is figuring out whether or not that's the right approach, whether we should consider giving multiple infusions over time, whether we should consider combining CAR-Ts with other treatments to improve the activity or efficacy, whether we should combine two different CAR-Ts together, things like that. 
So I think it's an area of active research, but right now it's a one time treatment.Yes, for now it is the way that it is approved as a one time treatment. But as we all know, it's not a curative treatment. While it gives you, you know, a really good response, a durable response, more so than we would have with any other treatments at this time. For example, in the fifth line setting, there's still need for improvement. 
Again, as of right now, the insurance commonly authorizes one CAR-T treatment. However, in our US Multiple Myeloma CAR-T Consortium, we have looked at patients who have had multiple CAR-Ts for example, if somebody had received CAR-T on clinical trial, whether that was a CAR-T using your own cells or a CAR-T using somebody else's cells, what we call allogeneic CAR-T, they have been subsequently treated with a commercial product. 
And our experience is very limited with this. It was actually only about five patients, but we saw that the response rate was essentially over 80%. For now, the way it's approved, it's a one time treatment, but in the future, you know, there is a possibility, especially as we get new targets and we learn more about sequencing, of sequencing of the agents we have available now, certainly could be a possibility 
But we are seeing good responses at present time. 
So CAR-T is a genetically engineered lymphocyte, and when they're given, they're supposed to be living drug and they go after the cancer cells, they proliferate, they replicate, they release the cytokines, and then the cancers. And if the patient does go into remission, theoretically they should go into memory state or hibernate. And in case there is a relapse, they're supposed to wake up and supposed to fight the cancer back again. 
Unfortunately, one of the problems that we are seeing in CAR-T is fantastic response, but it is not persisting and that could be from the t cell senescence and they get fatigued. So there are now trials going on in different aspects how to maintain the persistence of the CAR-T in the system. Now, in clinical trials we have found CAR-T by flow cytometry and other techniques many months and years after the initial first time infusion of CAR-T.

But we should be expecting to see that in majority of the patients active, ongoing in the memory system for that. adequates of CAR-Ts have been proposed also CAR-Ts associated with PD one inhibitor that actually accentuate the effect of the car T that has been proposed. So I think the future is very bright in CAR-T therapy in general in cancer. 
We don't know yet if repeated doses are going to be the way to go. It kind of makes sense. But we also don't know if the cells are going to mutate their BCMA so it no longer binds. And the CD19 we have a lot more experience about mechanisms of resistance? In some cases, CD19 disappears from the tumor and it gets modulated off. 
We don't have the target anymore. That may be different in BCMA. We don't know. The tumors are unfortunately get very smart, and they figure out ways to circumvent or get around the car t cell. And we just don't have a lot of experience in myeloma. Some patients still express BCMA sometimes they have lower levels. It also turns out BCMA is shed by the myeloma cells. 
So if there's a ton of BCMA protein in the blood, it may block the car t cell why because it's binding to the BCMA receptor on the T cell. So these are all sort of multiple approaches to trying to sort out what we're doing with this. So it may be you give multiple infusions and maybe you only give one you or you, the laboratory people figure out a way to make the T cells live longer in the patient so that you don't have to give multiple infusions. 
You may want to optimize the target. There are some that are using different types of binding to BCMA, different types of receptors that may have better affinity or bind to different parts of BCMA so you can decrease resistance. These are all new questions that we're going to answer in the future.