Pharmacists Play Pivotal Roles in Outpatient CAR T-Cell Therapy

Pharmacy Times® interviewed Molly Schiffer, PharmD, BCOP, stem cell transplant and cellular therapy clinical pharmacy specialist at Yale New Haven Hospital in Connecticut, on her presentation on the logistical and operational challenges of delivering cellular therapies in the outpatient setting at the 2025 American Society for Transplantation and Cellular Therapy (ASTCT) and Center for International Blood and Marrow Transplant Research (CIBMTR) Tandem Meeting in Honolulu, Hawaii.

During the interview, Schiffer emphasized the benefits of outpatient chimeric antigen receptor (CAR) T-cell therapy treatment, including reduced costs, improved access to therapy, and better quality of life for patients. She highlighted the importance of a well-trained, multidisciplinary team, including education for both health care providers and patients, and the establishment of comprehensive policies and procedures. Schiffer also discussed the operational necessities of a 24/7 outpatient clinic, direct admission pathways, and the critical role of compliance with regulatory programs, such as risk evaluation and mitigation strategy (REMS), to ensure the safe administration of CAR T-cell therapy in the outpatient setting.

Artificial intelligence depiction of genetically modified cells expressing chimeric antigen receptor. Image Credit: © Anastasiia - stock.adobe.com

Additionally, Schiffer explained that pharmacists play a key role in both direct and indirect patient care during outpatient CAR T therapy, from patient education on toxicity management to medication reconciliation and the verification of therapy protocols. Schiffer described pharmacists' involvement in managing both short-term and long-term side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), while ensuring the supply of essential medications tocilizumab (Actemra; Genentech).

Additionally, Schiffer outlined critical safety strategies, such as utilizing remote patient monitoring and telemedicine, as well as the importance of caregiver support and patient proximity to the treatment center. Schiffer also recommended resources for pharmacists seeking further education, including ASTCT training courses and Pharmacy Times Continuing Education offerings.

Pharmacy Times: What are the benefits of outpatient CAR T-cell therapy, and what do pharmacists need to keep in mind operationally in delivery of outpatient CAR T?

Molly Schiffer, PharmD, BCOP: The main reason why you'd want to do CAR T outpatient is really because you're able to minimize costs and resources to the hospital and the patient. It's increased access to therapy, so our patients are being able to be treated more so in the community, rather than having to be admitted to an inpatient setting. Also, it gives them improved quality of life, so that they're not spending days to weeks in the hospital.

But there is a lot of things that you have to keep in mind when deciding if a patient is a good candidate for getting outpatient CAR T, or if a hospital is a good hospital that's fit to be able to offer outpatient CAR T. Some of the operational considerations that you need to keep in mind is making sure that you know you have a multi-disciplinary team that is trained, ready, and willing to be able to offer outpatient CAR T as an option to patients. That [requires] making sure that everybody involved is well educated and able to make sure that the process goes smoothly. That means, from the very beginning, being able to offer a patient lymphoid depleting therapy, cell infusion in the clinic and then monitoring as well but keeping in mind that adverse effects do happen. So, all teams need to be able to admit patients and be able to smoothly transition their care from outpatient to inpatient, if necessary.

Education outside of just oncology, but to areas such as like the emergency department or the intensive care teams, is really important as well. With that being said, on top of training, you have to make sure the facility is able to actually offer outpatient as an option. You need to make sure you have a 7 day outpatient clinic that's available for patients to come into 24/7 on call, which has to be an option, so that if patients have any concerns at home, they know exactly who to reach out to. Then it's really helpful to have a direct admission pathway to avoid an emergency department if possible. For these patients, they're immunosuppressed, and often emergency departments have very high capacities of patients that it's not ideal for our CAR T patients to be sitting in the emergency department, waiting for a bed.

When also establishing an outpatient CAR T program, there are a lot of policies and procedures that come into play. So, some things that we'll talk about is just like, how to select a patient, what the monitoring frequency is, what the criteria for admission is, how to manage patients toxicity, and so I'll talk about a little bit of that later, but those are things that we need to develop into policies and procedures to make sure everybody's on the same page beforehand.

Then the last thing from like an operational perspective to keep in mind is that there is a lot of like auditing and compliance that comes along with CAR T, so they are all part of the REMS programs. So, there's compliance that needs to be considered. There's going to be standards of practice within our own practice that have to be followed. Then all the data and patients are then also reported to the CIBMTR and then have to comply with the [Foundation for the Accreditation of Cellular Therapy] accreditation standards. So, these are all really important operational considerations to keep in mind before a hospital is able to open up outpatient CAR T as an option.

Pharmacy Times: What is the role of the pharmacist in outpatient CAR T-cell therapy in direct and indirect care for patients?

Schiffer: Patients have a very large role when it comes to CAR T. From a direct patient care perspective, [pharmacists] are involved in patient and caregiver education, which is really important from the beginning and throughout, to make sure that patients know what they're getting themselves into, know what toxicities to be looking out for, and it’s important for the caregivers to know how to be monitoring them for these different toxicities and when to escalate when they're not able to handle things at home anymore. So, education is a huge part of the pharmacist role.

Additionally, pharmacists help with chemotherapy, order entry, verification of the lymphodepleting therapy, just going through medication, reconciliation with patients to make sure they're on all of the right medications, helping make sure that they understand all the supportive care that goes along with CAR T. From an operational standpoint, one of the REMS requirements is that all CAR T patients have to have a tocilizumab set aside for them specifically. So, we have to confirm the tocilizumab supply before any CAR T patient starts their lymphodepleting therapy and get their infusion. The pharmacist is also involved in verifying the cells once arrived and helping with labeling the cells. So that's something that they're involved in.

Then the last thing is just both short and long term side effect monitoring. So, in the short term, pharmacists are pretty involved in helping with the management for CRS, ICANS, cytopenias. Then also some of the long term side effect monitoring, so things like, when are they due for IVIG? When should we start thinking about immunizations? So those are kind of some of the more patient, direct patient care roles that a pharmacist can have.

Then from a non-direct patient care perspective, more behind the scenes, going back to talking about tocilizumab, so we want to make sure that we have enough stock, so that when a patient is coming in, we have no concerns with making sure that we have that supply for them, making sure that things are sequestered appropriately, if necessary. There's always biosimilars coming out, so are biosimilars for tocilizumab an option or not, and having those conversations with the team.

Other things to prepare for getting patients outpatient CAR T is order sets. So, within the electronic medical record, order sets are really helpful for patients that are being admitted. So having chemotherapy order sets, treatment plans, or direct admission order sets to make sure that all of the correct medications, labs, tests are ordered, so if patients do end up on like a non-oncology floor, such as in the emergency department or the intensive care unit, providers that maybe aren't as familiar with CAR T know exactly what to order for these patients.

Then like management as well for CRS and ICANS, so the toxicity managements are pretty well defined for each product, and so it's helpful to have those all laid out in an electronic medical record, treatment plan, or order set as well.

Some other things that comply with the REMS requirements: All the patients have to have wallet cards, standardized education material, and so those are some things that pharmacists can help make sure that the patients are able to get beforehand. Then, just also as new CAR T products are being approved, helping with the new formulary consideration, so presenting these new CAR T products to the pharmacy and therapeutics committee, helping integrate them into the electronic medical record, building treatment plans and making sure all of these REMS requirements play into new products that get approved.

Pharmacy Times: What are some critical pharmacist-driven safety strategies in the outpatient setting to mitigate the risks associated with cellular therapies?

Schiffer: Those are really important, especially in the outpatient setting, to make sure that patients fully understand what to be looking out for and then how to treat it. So, one thing is that anybody who's getting CAR T outpatient will continue coming into the clinic for in-person clinical assessments. So, one of the key things that we keep in mind when deciding if someone is appropriate for CAR T is how far away they live from the treatment center. So, every institution has specifics, but I'd say, on average for our institution, it's required that a patient lives within 1 hour of the treatment center for us to even consider them for outpatient treatment. So, it's important that they're close enough that they can continue coming into clinic daily, or however frequently they need to after their CAR T.

The other thing that's really important, and again, plays into if a patient is a good candidate for CAR T is their caregiver involvement and support. So, we need to make sure that these patients have a good support system at home if they're going to be getting outpatient CAR T. Someone that's able to be involved in all the discussions, all the education, all the clinic visits, so that they know what to be looking out for. Then they're also just a really helpful tool for practical medical emotional support for the patient. So, it's really important that these key things are put into place before even deciding whether the patients an outpatient candidate, to make sure we're able to thoroughly monitor for the toxicities they might experience at home.

Something else that we're able to do in the outpatient setting, and that some institutions do is use remote patient monitoring. So, there's a couple different things that this could be made up of. Some institutions use wearable electronic devices. Some benefits of that is that it will continue to monitor the patient's conditions continuously between their clinic visits. You can identify if they have CRS or ICANS quicker, give them prompt care, and then this also helps with patient and caregiver awareness of like, exactly what to be looking out for.

But with that being said, there are some negatives of it. If a patient is constantly watching what their vital signs, they might kind of increase patient anxiety. It is also a more costly option to add on board. As always, it's really relying on like technology. So, there can always be errors with technology that we just have to keep in mind with these monitoring wearable electronic devices.

Another option that might not be as costly or that patients can use is just sending them home with monitoring kits. So, these monitoring kits are just simple kits that include the key things that can help monitor vital signs, so things like a thermometer, a pulse oximeter, and just teaching the patient and the provider how to use these to monitor for signs of CRS.

Then the last thing is that we can utilize not just in-person visits, but also telemedicine visits. So, sometimes patients might come into clinic in the morning, but might also then need a telemedicine visit in the afternoon, or as they get a little bit further out, if they don't need to be in the clinic every day, we can use utilize our telemedicine visits to talk to the patient and the caregiver and see how they're doing at home without actually making them come into the clinic. So those are kind of the main things that we can use to monitor for toxicity.

Then there is also a lot of data that is coming out looking at various things that we can use to kind of prevent CRS and ICANS from happening, and some of that which we'll talk about more in the presentation at Tandem is there are certain JAK1 inhibitors that are being studied to help prevent toxicity, and then different lymphodepleting regimens might have more or less evidence of CRS or ICANS, so just some things to consider with specific patients on what they might be a candidate for if they're at high risk for CRS or ICANS.

Pharmacy Times: What resources or training opportunities would you recommend for pharmacists who want to expand their expertise in cellular therapy?

Schiffer: I think ASTCT has a really great opportunity for pharmacists. In April every year, we have the fundamentals of [hematopoietic cell transplantation] training course. So that's something that's open to pharmacists, providers, nurses, basically anybody that wants to get a better understanding of cell therapy.

Then, in addition to that, every 2 years, an ebook comes out that most of the chapters are written by pharmacists. So, it's basically how I learned everything I could about cell therapy to see exactly the best things a pharmacist needs to know about every aspect of cellular therapy.

On top of that, Pharmacy Times has great free CE that cover various different cellular therapy topics and aspects that go along with cellular therapy.