CAR-T Cell Therapy Use in B-Cell Malignancies - Episode 2
Krishna V. Komanduri, MD: So, I want to actually move to considerations, and I think just for the audience that may not yet be familiar with treating these patients primarily, Michael, maybe you can talk to us about where patients get CAR T-cell therapy and who administers this, and does this require hospitalization at this time?
Michael Pulsipher, MD: That’s a very important question, and David and Steve had alluded to the fact that on-target but nontumor side effects can lead to a lot of complications associated with CAR T’s that we’ll talk about in a little bit more detail later. But many of the trials that have been designed to administer this agent have been based on mainly doing this as an inpatient procedure. But what we found is that a decent number of patients can be treated outpatient and have this as an outpatient infusion. But I think we’re transitioning right now. It’s going to differ depending on which CAR you’re using. Because, some CARs can have very early fevers and other toxicities. Other CARs have much less of a chance of having significant toxicities. So, that particular question that you ask, Krishna, is something that we’re actually really resolving. Some are designing this to be given as an outpatient and others may need to be given inpatient.
Krishna V. Komanduri, MD: And I think to be fair, so far most of the patients have been treated, other than at very highly specialized centers, and have been managed mostly in the inpatient setting. So, I think as we better understand the complications and who will develop those complications, we will see a transition. But the vast majority of patients, at least initially, will likely be treated in the inpatient setting.
I want to move to another practical point that’s general across these products, which is, what about the timing required to produce these cells? And, Steve, especially as a lymphoma expert where you sometimes see rapidly growing disease, how does that timing vary and how does it affect the therapy?
Stephen J. Schuster, MD: I think, currently, the products can be prepared within 17 to 22 days, depending on which CAR you’re talking about. And that seems like a relatively short period of time but in a very sick patient who has a rapidly progressing disease, it could be a critical amount of time. So, in some cases, patients get what we call bridging therapy; therapy to stabilize them prior to getting the lymphoid depletion chemotherapy that we give prior to giving the CAR cell infusions. So, it can be challenging at times. And it’s not necessarily the 17 to 22 days that’s the problem, it’s also the production slots. How many products can you make at the same time in a given facility? A facility may not be able to accept products because they’re making as many as they can at that point in time. So, it’s one thing to talk about how many days it takes to make a CAR cell, it seems rather short, but the logistics are different and it can be long, and it can be challenging to manage these patients in preparation for this therapy.
Michael Pulsipher, MD: Well, I think one important point that needs to be made with that is that when we have very complex and resistant malignancies, our tendency is meant to treat them incredibly intensely, get patients into the best remission possible. And one thing we’re finding is that CARs are so potent that we may not need patients to be in a deep remission prior to giving their CARs. We’ve changed our philosophy with ALL to keep the patient alive, give them therapy that controls the disease but don’t hurt them prior to giving the CAR because we have drop off of patients who are not able to get the CARs because they get too sick or they have fatal complications prior to the CAR. So, we’re really changing the way we think about these patients.
Stephen J. Schuster, MD: That’s exactly the way we’ve been approaching the lymphoma patients. The idea is to stabilize the patient, keep them in good shape, but not to try to achieve a deep remission. The CARs are the therapy that’s aimed at getting the patients into remission.
David Maloney, MD, PhD: But I also think it’s important to remember, it’s the total package. So, we’re all starting from when we’re giving the CARs, but in reality, it starts with getting the patient on the service, evaluating their disease, dealing with their insurance, then collecting cells by apheresis, sending them off to whoever is going to make the cells, or make them in your own facility, then waiting the 17 to whatever days to get the cells back, then give lymphoid-depleting chemotherapy the CARs, and then observing the patient over the next month. So, the treatment course is still on par with an autologous transplant. That is the best way I think about it. And it does require just to be done in specialized centers.
Krishna V. Komanduri, MD: All great points to be made. The only other thing I would add to that is that as we look at the trial results, some of these trials allow bridging therapy and some did not. We should make sure that as we interpret those trial results that we consider that, because obviously a trial where a patient was not allowed to get bridging therapy might end up with a different patient upset than one where gene therapy was allowed, and that’s important going forward as well.
Transcript Edited for Clarity