David Maloney, MD, PhD: Let’s change the subject slightly here. Do you guys feel that there’s an opportunity to give this kind of treatment in an outpatient or community type of setting, rather than in the intense university BMT [bone marrow transplant] programs that most of us are all affiliated with? Fred, what do you think?
Frederick Locke, MD: As we know, CAR [chimeric antigen receptor] T-cell therapy can lead to cytokine release syndrome [CRS] and neurologic events. Those toxicities can be very severe. With the different CAR T-cell products, we’re seeing that the rates of those severe toxicities can be different. I do believe that centers that administer CAR T-cell therapy need to have a minimum knowledge of how to manage those toxicities, and be comfortable in rapidly admitting patients to the inpatient side when those things happen. In my experience, where we do outpatient CAR T-cell therapy, you actually need more infrastructure to administer outpatient CAR T-cell therapy than you do to administer it in the inpatient setting. You need to have the clinical setting where you can see a patient frequently, and you need to have providers who are vigilant and there to see the patient at a moment’s notice when they do get sick.
Caron Jacobson, MD: And on top of that, I think we all are at incredibly busy centers where inpatient capacity actually exceeds the number of inpatient beds. And so, we find there’s an insurance policy to electively admitting a patient for their CAR T-cell therapy because we can plan that. It’s the unplanned admissions where we have a really hard time. Sometimes it can take patients 12 to 24 hours to get a bed if they’re coming to us in an unplanned way. We have to create the infrastructure to circumvent that, which is one of the holdups that we’ve had at our institution.
Max Topp, MD: But I think we have some efforts to stratify our patients. We know the patients who are at risk. If they are a very low-risk patient, with a low tumor burden, at a less inflammatory state, this patient could be treated in the outpatient setting. Whereas for the high-risk patients with high tumor burden, those are the ones we really want to manage in an inpatient setting.
David Maloney, MD, PhD: I know that at our center we have considerable outpatient experience now with lisocabtagene maraleucel. I think I’ve treated all of the patients in the outpatient setting. I’ve also treated quite a few patients with tisagenlecleucel in the outpatient setting. I’ve not treated anybody with axicabtagene ciloleucel in the outpatient setting. They stay in the hospital. But we saw, at this meeting, emerging data with lisocabtagene maraleucel from the trials that were presented and the pilot study of patients treated largely in community centers as well as academic centers. A lot of those patients were treated as outpatients. They were at an earlier stage in disease—first relapse, in some cases—or transplant-ineligible, and I think that the data we saw revealed that for those patients who could be treated as an outpatient, many of them actually stayed outpatient.
But I really want to echo Fred’s comments: To do this as an outpatient, it’s really dependent on the center. It’s not necessarily just the product. I think some products are more easily done in the outpatient setting. The 4-1BB constructs have a later onset. You can get to day 4 or 5 before they have to be admitted. And there may be major advantages, as you said, about reimbursement for this. But also, just the incidence of cytokine release syndrome being less than half of the patients also is conducive to keeping those patients as outpatient.
I think everyone is quite excited about that, but it does require a team. You have to have 24x7 [around the clock] triage. You have to have 24x7 ability to directly admit the patient to the hospital. I think, ideally, they don’t go through an emergency room. They have to go to a team that knows how to take care of them. They have to stay within 30 to 60 minutes of the center. They have to have a qualified caregiver with them who can at least call 911 or call the center to get them in at the first fever. Encouragingly, we saw that fever was the most common reason, and most of those people didn’t require escalation of care once they got to the hospital.
Caron Jacobson, MD: Correct me if I’m wrong, but the pilot study actually mandates that all patients be treated in the outpatient setting. And I think it’s 17 or 18 centers, for which the majority are actually community centers that have not participated in CAR T-cell therapy before. Is that right?
David Maloney, MD, PhD: Yes, but I think that there’s a big vetting of those centers. They essentially have to qualify for many of the things that you would have to do for FACT [Foundation for the Accreditation of Cellular Therapy] accreditation, although it’s not FACT accreditation. Because if you think about it, there are still a number of issues. Chain of custody went from the apheresis to the chain of custody, to getting the cells back, having the standard operating procedures to treat CRS and manage patients. And then, having all of the procedures. So I think even if these are “community,” they’re high-level community centers.
Frederick Locke, MD: Yes. I think it’s clear that administering CAR T-cell therapy in the outpatient setting and keeping the patient out of the hospital is desirable for many reasons. However, to do that, bottom line, you have to have some significant infrastructure. FACT accreditation would sort of prove that, but it may not be the only way. But I think as more CAR T-cell therapies come forward, it’s important to understand that they’re probably going to still be utilized at larger referral centers, as transplant is. That doesn’t mean there won’t be smaller programs that pop up, but there has to be infrastructure around that.
David Maloney, MD, PhD: But I think one of the big problems we have is we’re not treating everybody who’s eligible for this disease, right? The estimate is somewhere in the 10% to 20% range that we’re actually reaching. And I know for a fact that where I am, in Seattle, for example, patients from Montana, a lot of them don’t want to go more than 30 minutes from their house. Clearly, we may need to not just do it in the major centers but develop these closer-to-home approaches. And maybe some of these products will be more conducive of that.
Max, you mentioned that you kind of choose patients who you’re going to do outpatient or not, based on characteristics. We personally don’t, and we have treated people who I would think are quite sick and are very high risk. Because it’s not 100% predictable whether they’re going to get into trouble, and even then, they may not get into trouble for 4 or 5 days after. I think if they do have good caregivers and you have a situation where you have a great team, you might be able to do this. But it’s not for everyone.
Max Topp, MD: I totally agree. It’s all experience. You have to build up that experience, and then you can start to move it out into the outpatient situation. I completely agree with that, David.
Jason Westin, MD: We’ve treated 300-plus CAR T-cell patients, and to date, have not done so in the outpatient setting primarily because of axicabtagene ciloleucel, but also because the infrastructure on the outpatient side, as Caron mentioned, to move to the inpatient side is daunting. And so, I think the idea that this can be done in the outpatient setting at community centers, ideally, those already have done inpatient care and have the knowledge to do that. Because I think the patient selection would be great if you could decide who you can treat in Montana and not send to Seattle. I think that’s tricky.
David Maloney, MD, PhD: Also, there’s a learning curve, right? Remember back when we first started doing CAR T-cell therapy? We had to learn our way in the management. Even the first few times you see this, cytokine release syndrome can be pretty scary; and neurologic toxicity can be worse.
Frederick Locke, MD: We treated the first patient on the ZUMA-1 trial, and it was quite scary seeing that patient. You needed to see a few patients before you really felt comfortable.
Caron Jacobson, MD: I think that for a standard CAR T-cell course, treating a handful of patients is sufficient. But now we are 3 years into treating patients with CD19 CARs. I still, on a 3 or 4 times a year basis, see something that totally shocks me and is totally new. There are still things that I can’t explain. So I think we’re at the tip of the iceberg here in terms of what we have to learn.
Transcript Edited for Clarity