Addressing Logistical Challenges of CAR T Therapy Administration in Inpatient, Outpatient Settings

Pharmacy Times interviewed Craig Freyer, PharmD, BCOP, a clinical pharmacy specialist at Penn Medicine in the University of Pennsylvania Health System, and Andrew Lin, PharmD, BCOP, an oncology pharmacy specialist at Memorial Sloan-Kettering Cancer Center, to discuss their presentation at the recent ATOPP 2021 summit on re-examining the why, who, and where of chimeric antigen receptor T-cell (CAR T) therapy.

Alana Hippensteele: What are examples of some of the logistical challenges related to CAR T therapy administration in the inpatient and outpatient setting?

Craig Freyer: I think we need to think about the various steps of CAR T therapy and look at some of the challenges associated with each step. Some of these steps are, of course, shared whether you're giving it inpatient or outpatient, and then some of them are more specific to outpatient administration.

So, you first have to look at your ability to successfully manufacture a product for your patient, and often times that has to do with the lymphocyte count at the time of pheresis. Within the studies, there are various lymphocyte thresholds that were necessary to increase the likelihood of manufacturing a product successfully for your patient, and oftentimes the lymphocyte count is a function of your cumulative lymphotoxic therapies that were previously given prior to CAR T therapy and how long those have been spaced from pheresis. So those are some things that we discussed in the presentation in terms of timing and use of lymphotoxic agents.

Another thing that has to be considered prior to getting your patient to CAR T therapy is whether they'll need bridging therapy in the interim, which essentially stabilizes their disease between the period of leukopheresis and lymphodepleting chemotherapy in an attempt to more favorably impact the outcome of CAR T therapy to maintain the patient until you are able to actually give them the CAR T infusion.

We get lymphodepletion, and the lymphodepletion is typically the same whether you're inpatient or outpatient, and it varies based on the product you're selecting, whether it's fludarabine or cyclophosphamide (Flu/Cy) for most of them, or whether it's a possibility to use bendamustine in the scenario of tisagenlecleucel.

Unfortunately, we had a shortage of fludarabine last year, which led us to change most of our lymphoma patients to receive bendamustine as lymphodepletion. Various abstracts in other publications have been put together looking at bendamustine as lymphodepletion, and the outcomes look very similar as that observed with Flu/Cy, but potentially even with a little less myelosuppression.

We then further got into the use of out of spec, or OOS, CAR T products, and the fact that for some of these patients, their product that you get from the manufacturer doesn't meet the FDA specification, but can still be given either through a managed access program or through a specific IND, and oftentimes that is done rather than trying to rephrase and remanufacture a product for the patient.

Then, of course, once you get to the day of infusion, do you do it inpatient or outpatient? Oftentimes, centers are doing these things exclusively inpatient because of the potential risks and because of the fact that many of the people in the clinical trials were in fact treated outpatient. But we have extensive experience here at Penn using outpatient CAR T therapy, and generally, for lymphoma, we have criteria that buys them the inpatient stay.

If they don't have things such as organ dysfunction, bulky disease, or very symptomatic disease, oftentimes they will meet our criteria to get their infusion outpatient. Oftentimes, that just means that they have to be seen frequently in the clinic weekly from day 8 to 28. Day 2 and day 4 after infusion, we see them twice the first week. They call if they have a fever, they call if they have any changes in mentation or other symptoms of CRS or neurotoxicity. They have to be within an hour driving distance and have a 24-hour caregiver for 4 weeks.

In general, in our experience—we put together an abstract on it for ASH a few years ago—most of these patients are able to remain outpatient and only a small number of patients, less than half, are actually admitted to the hospital for toxicity management.

Other sites have reported similar feasibility of using select CAR T-cells outpatient, so I think there's a growing experience with using CAR T infusion outpatient for 4-1BB stimulated products, but I think CD28 stimulated products are still mostly being used as inpatient infusions at the current time, until we get a little bit more experience in terms of toxicity management.