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The Logistics of Building a CAR-T Program

Insights From: Nilanjan Ghosh, MD, PhD, Levin Cancer Institute; Leo Gordon, MD, Northwestern Memorial Hospital; Matthew Lunning, DO, University of Nebraska Medical Center
Published: Monday, Dec 10, 2018



Transcript: 

Nilanjan Ghosh, MD, PhD: The administrative challenge for offering CAR-T therapy starts with the initial negotiation between the center that offers CAR-T therapy and the manufacturing facility. This can be a very time-consuming process. There is a contractual process, which is set up in a way to standardize the collecting, storing, freezing, and receiving cells, in addition to preparing them for administration. They have to meet whatever requirements that are set by the company, and there can be logistic challenges because the same apheresis facility will be collecting and handling cells for CAR-T therapy in addition to doing the collection of stem cells for autologous and allogeneic transplant. We need to create a process in which the standards for CAR-T therapy are met, but which don’t interfere with function of the apheresis facility.

The next part of this is the clinical challenge. It is important to have a team of providers, physicians, and advanced care providers who will be able to screen and find eligible patients for CAR-T therapy and manage them throughout the process. Administering the CAR-T therapy and managing them through the side effects is also essential. This needs a tremendous amount of coordination between the hematology team, intensive care team, and neurology team. It is imperative they understand the algorithms and protocols, which are in place for management of cytokine release syndrome [CRS] and neurotoxicity.

It’s also critical to have tocilizumab [Actemra], the IL [interleukin]-receptor antagonist, available for patients receiving CAR-T therapy at any time of day, because the need may arise on a Friday night or on a weekend. It’s also important for us to understand that most of the toxicities, even though they could be common and reversible, have possible mortality. As a team, it is important to take care of the patient if they’re critically ill, with the hope of reversing this toxicity.

Matthew Lunning, MD: Our CAR-T cell program grew within our lymphoma disease-based team, within which we also deal with allotransplant and leukemia. We are a FACT [Foundation for the Accreditation of Cellular Therapy] accredited facility, which is an important part of the CAR-T cell process.

With regards to using the approved constructs, each CAR-T cell program has a REMS [Risk Evaluation and Mitigation Strategy] program. For axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel], I had to use a REMS-based program. We broke it down to different institutions that are going to do different things. With regards to the REMS, who needs to be present? Who needs to be educated about CAR-T cells? Who needs to do the REMS program? The person who’s dispensing the CAR-T cells, which in our case is the cell manufacturing facility personnel, certainly need the REMS program, as well as those who are administering the treatment.

We had our advanced practice providers take the REMS program for extended education. They are getting an education from people like myself or colleagues who are treating patients with CAR-T cells. We’re also educating neurologists and the ICU staff regarding adverse side effects.

We have several strategies that we’ve employed in order to help facilitate this, to ensure we are using the best practices regarding CAR-T cell care and patient management. It doesn’t just start with me, the prescriber, or the nurse who administers—it’s truly a team event. We’ve taken this to the level of creating CAR-T cell pagers so that if a patient shows up in our emergency room, there is a direct message sent to a pager to notify the required personal in the ER.

We’ve also worked with our IT department to create a banner or headline indicating CAR-T cell patients who arrive to the ER, so that we can at least be involved in the decision-making process to discern whether this is a neurotoxicity or CRS event, or something else.

We’ve also taken time to make sure we can manage neurotoxicities. Did a patient experience CRS? How were they treated by creating shortcuts embedded within our electronic medical records? You have to think globally. With a complex treatment like this, you cannot do it by yourself. We experienced this and grew though it with our clinical trial, which we used to bridge into commercial experience, to develop a team that meets frequently with physicians. We also have a nurse case manager who helps navigate our CAR-T patients through the apheresis process. With inpatients, we see if they are experiencing neurotoxicities. How was it managed and what are their counts? That segues nicely to the post–CAR-T cell outpatient experience to help manage and understand what their CAR-T was in patients, and try to transcend that into better outcomes and management as an outpatient.

You want to have the people educated that need to be educated. I don’t necessarily think you can ask the ICU doctor to manage the CRS or neurotoxicity. In the CAR-T cell space, we want to be involved and help with the CRS in the neurotoxicity events. We want at least to be in the discussion about what the differential is, because it may not be CRS, but instead gram-negative or sepsis. It may be the uncovering of another neurological disorder that wasn’t known before. If they aren’t asked, is CRS part of the differential?

Leo Gordon, MD: There’s 2 facets to CAR-T research. One is clinical research, which I think has to go on. Just because we have 2—and soon perhaps 3 products that are approved—doesn’t mean that we should stop doing research in clinical trials with these agents. To build a research program one has to have a robust clinical research team, and the means to carry out pretty complicated clinical trials. In the community setting or in the commercial setting, if you will, I think building a CAR-T program is perhaps similar to what we and the centers have done with stem-cell transplantation. One has to have a team that’s experienced in the use of these cellular products.

It’s important to receive accreditation from FACT [Foundation for the Accreditation of Cellular Therapy], which is the stem-cell transplant accreditation agency. It is beginning to apply now to cellular therapy, including CAR-T. You have to have clinical trials and regulatory systems in place. For commercial use, you have to have the appropriate so-called “REMS” training so that everybody involved in the care of these patients has an idea of what to expect in terms of toxicity. Down the road, especially as the cost of these things evolves, we’re going to be looking for ways to give this so it’s not as costly, and perhaps doing this for outpatients I think is feasible. We’re just beginning to do that. I know they’re doing that at the Fred Hutchinson Cancer Research Center in their immunotherapy [I-O] center. There are some institutions that are beginning to treat patients as outpatients, just like is done for some patients who have received stem-cell transplants. Having CAR-T as part of an existing ongoing stem-cell transplant program is probably the right idea.

Transcript Edited for Clarity
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Transcript: 

Nilanjan Ghosh, MD, PhD: The administrative challenge for offering CAR-T therapy starts with the initial negotiation between the center that offers CAR-T therapy and the manufacturing facility. This can be a very time-consuming process. There is a contractual process, which is set up in a way to standardize the collecting, storing, freezing, and receiving cells, in addition to preparing them for administration. They have to meet whatever requirements that are set by the company, and there can be logistic challenges because the same apheresis facility will be collecting and handling cells for CAR-T therapy in addition to doing the collection of stem cells for autologous and allogeneic transplant. We need to create a process in which the standards for CAR-T therapy are met, but which don’t interfere with function of the apheresis facility.

The next part of this is the clinical challenge. It is important to have a team of providers, physicians, and advanced care providers who will be able to screen and find eligible patients for CAR-T therapy and manage them throughout the process. Administering the CAR-T therapy and managing them through the side effects is also essential. This needs a tremendous amount of coordination between the hematology team, intensive care team, and neurology team. It is imperative they understand the algorithms and protocols, which are in place for management of cytokine release syndrome [CRS] and neurotoxicity.

It’s also critical to have tocilizumab [Actemra], the IL [interleukin]-receptor antagonist, available for patients receiving CAR-T therapy at any time of day, because the need may arise on a Friday night or on a weekend. It’s also important for us to understand that most of the toxicities, even though they could be common and reversible, have possible mortality. As a team, it is important to take care of the patient if they’re critically ill, with the hope of reversing this toxicity.

Matthew Lunning, MD: Our CAR-T cell program grew within our lymphoma disease-based team, within which we also deal with allotransplant and leukemia. We are a FACT [Foundation for the Accreditation of Cellular Therapy] accredited facility, which is an important part of the CAR-T cell process.

With regards to using the approved constructs, each CAR-T cell program has a REMS [Risk Evaluation and Mitigation Strategy] program. For axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel], I had to use a REMS-based program. We broke it down to different institutions that are going to do different things. With regards to the REMS, who needs to be present? Who needs to be educated about CAR-T cells? Who needs to do the REMS program? The person who’s dispensing the CAR-T cells, which in our case is the cell manufacturing facility personnel, certainly need the REMS program, as well as those who are administering the treatment.

We had our advanced practice providers take the REMS program for extended education. They are getting an education from people like myself or colleagues who are treating patients with CAR-T cells. We’re also educating neurologists and the ICU staff regarding adverse side effects.

We have several strategies that we’ve employed in order to help facilitate this, to ensure we are using the best practices regarding CAR-T cell care and patient management. It doesn’t just start with me, the prescriber, or the nurse who administers—it’s truly a team event. We’ve taken this to the level of creating CAR-T cell pagers so that if a patient shows up in our emergency room, there is a direct message sent to a pager to notify the required personal in the ER.

We’ve also worked with our IT department to create a banner or headline indicating CAR-T cell patients who arrive to the ER, so that we can at least be involved in the decision-making process to discern whether this is a neurotoxicity or CRS event, or something else.

We’ve also taken time to make sure we can manage neurotoxicities. Did a patient experience CRS? How were they treated by creating shortcuts embedded within our electronic medical records? You have to think globally. With a complex treatment like this, you cannot do it by yourself. We experienced this and grew though it with our clinical trial, which we used to bridge into commercial experience, to develop a team that meets frequently with physicians. We also have a nurse case manager who helps navigate our CAR-T patients through the apheresis process. With inpatients, we see if they are experiencing neurotoxicities. How was it managed and what are their counts? That segues nicely to the post–CAR-T cell outpatient experience to help manage and understand what their CAR-T was in patients, and try to transcend that into better outcomes and management as an outpatient.

You want to have the people educated that need to be educated. I don’t necessarily think you can ask the ICU doctor to manage the CRS or neurotoxicity. In the CAR-T cell space, we want to be involved and help with the CRS in the neurotoxicity events. We want at least to be in the discussion about what the differential is, because it may not be CRS, but instead gram-negative or sepsis. It may be the uncovering of another neurological disorder that wasn’t known before. If they aren’t asked, is CRS part of the differential?

Leo Gordon, MD: There’s 2 facets to CAR-T research. One is clinical research, which I think has to go on. Just because we have 2—and soon perhaps 3 products that are approved—doesn’t mean that we should stop doing research in clinical trials with these agents. To build a research program one has to have a robust clinical research team, and the means to carry out pretty complicated clinical trials. In the community setting or in the commercial setting, if you will, I think building a CAR-T program is perhaps similar to what we and the centers have done with stem-cell transplantation. One has to have a team that’s experienced in the use of these cellular products.

It’s important to receive accreditation from FACT [Foundation for the Accreditation of Cellular Therapy], which is the stem-cell transplant accreditation agency. It is beginning to apply now to cellular therapy, including CAR-T. You have to have clinical trials and regulatory systems in place. For commercial use, you have to have the appropriate so-called “REMS” training so that everybody involved in the care of these patients has an idea of what to expect in terms of toxicity. Down the road, especially as the cost of these things evolves, we’re going to be looking for ways to give this so it’s not as costly, and perhaps doing this for outpatients I think is feasible. We’re just beginning to do that. I know they’re doing that at the Fred Hutchinson Cancer Research Center in their immunotherapy [I-O] center. There are some institutions that are beginning to treat patients as outpatients, just like is done for some patients who have received stem-cell transplants. Having CAR-T as part of an existing ongoing stem-cell transplant program is probably the right idea.

Transcript Edited for Clarity
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