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Immunotherapy - Chimeric Antigen Receptor (CAR) T Cells - Overview and Clinical Applications
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Karen Anderson discusses Immunotherapy - Chimeric Antigen Receptor (CAR) T Cells - Overview and Clinical Applications at ONS Congress 2017. For the ability to view on your mobile phone please visit us at MinuteCE.com.

This transcript is software driven, please understand there may be errors.  Should any inaccuracies or omissions be found, please notify transcripts@MedEdOTG.com for correction.

Hi I am Karen Anderson. I am the clinical operations manager of the Bezos Family Immunotherapy Clinic. The Bezos Family Immunotherapy Clinic is located at the Seattle Cancer Care Alliance and the SCCA is in affiliation of the Fred Hutch University of Washington in Seattle Children's. We are a clinic that provides cellular immunotherapies to patients and some of the other trials actually include chimeric antigen receptor T-cells.

What are CAR-T cells? CAR-T cells are genetically modified T-cells in which a receptor has been inserted that is targeted towards a specific antigen and when we use these for cancer therapies, the antigen target should be present on tumors so that these T-cells can essentially go and interact with this antigen and kill the tumor. There have been remarkable successes with this therapy today especially with the CD19 antigens that are expressed on B-cell lymphocytes and B-cell malignancies. So this has opened up a whole new world of therapeutic options for both adult and pediatric patients.

How do we deliver these therapies to patients? It’s actually a complicated treatment plan for patients receiving these therapies. This is not a therapy where a doctor can just write a prescription and it’s given once in the infusion room and the patient is done. There is actually quite a bit of care coordination that is required to collect these T-cells to engineer them and then to reinfuse them into patients and to monitor for toxicities long term.

Some of the toxicities we can see for these therapies are significant and nurses should know about these. The two big ones that are I think new are cytokine release syndrome and neurotoxicity that can be associated with these CAR-T cells. Tumor lysis is certainly a concern because we can affect massive tumor kill with these CAR-T cells as they are interacting with their antigen. We can see chemotherapy related toxicities and then one of the other interesting ones is on target and off tumor toxicities. If you use the example of B-cell malignancies, CD19 is expressed on both malignant and non-malignant T-cells. If CAR-T cells are killing cells with CD19 they can be killing both the tumor as well as normal B-cells. This can actually happen where patients have low gamma globulins related to killing of those B-cells and they may require immunoglobulin supplementation while these B-cells are ablated.

CRS is a neurotoxicity we need to talk about just a bit more. CRS is an inflammatory process that is related to cytokine release that happens when these CAR-T cells interact with their antigen target. I have listed several of the cytokines that have been implicated in this process. It is not at all an inclusive list but IL-6 seems to be a primary mediator of cytokine release syndrome. That is the important one to know because one of the medications that we actually use to treat progressive CRS is tocilizumab which helps bind, helps essentially block the receptors for IL-6. We sometimes will do this with significant CRS to minimize patient toxicity.

CRS can be on a spectrum. On the mild end, a patient might just feel like they have the flu. On the severe end, we can see significant hypotension coagulopathies in DIC, multi organ dysfunction and severe neurotoxicities. Management of these symptoms can be intensive from a nursing perspective. We need to be aware and monitoring for new onsets of these symptoms; for stable vital signs; for patients to report changes in how they are feeling. There also needs to be a system in place to be able to quickly react to these symptoms when they occur so that we can intervene early enough.

Neurotoxicity is associated with cytokine release syndrome and CAR-T cell administration and it can present from mild to severe symptoms. Aphasia, word finding difficulties, confusion are some of the presentations that we see of neurotoxicity in these patients and it can progress to seizures, delirium and cerebral edema and death. This is an area were nurses can actually play a big role in monitoring and supporting patients that may be experiencing neurotoxicity. It's important to be able to the establish a baseline neuro status for patients and this can be done through full neurologic assessments through mini mental status exams, other neuro, psychological types of testing. Then those can be serially monitored as patients go through this therapy.

Nurses at the bedside are sometimes involved in neurotoxicity just by assessing things like how patients are able to write their names, how they are able to answer questions and orientation as well as other types of neurological testing. Anti-seizure prophylaxis is common and we want to assess for other potential causes so that we don't overlook things. If it is neurotoxicity related to CRS then often times we are going to consider treating and usually the first medication that we would treat with is corticosteroids because of its ability to be lymphotoxic against those T-cells that may be interacting. We do not really understand why neurotoxicity happens. It is associated with the overall inflammatory picture of CRS it is believed.

One of the things that are important to take away is that neurotoxicity actually will often time resolve with time. While it may be very disconcerting and rather upsetting and sometimes frightening for this to occur, if we give patients time, many times this will resolve without long term sequelae.

What do nurses need to know about CAR-T cells? Well if you are administering the products you need to know how to give them. Pre medications are common and then monitoring for types of infusion reactions while the T-cells are being infused. We want to know what our baselines are for our patients and routinely assess them for things like fever, changes in neuro status, infection and pain. Where these patients may be monitored can vary depending upon the setting and the toxicities associated with the therapy. Some patients may be appropriate for the outpatient setting but in many settings, an inpatient setting is going to be a more appropriate setting for patients that may be at high risk for experiencing toxicities and for very acute toxicities from CRS, generally ICU management may be warranted.

There are many laboratory assessments that we do. Labs on a daily basis to look for cytopenia; overall pictures of inflammation coagulopathies and organ toxicities.

That concludes my presentation.