Medicare, Medicaid Policy Challenges Facing CAR-T Therapies

By Zachary Bessette

Podcast Series: Michael R. Bishop, MD, Director, Cellular Therapy Program, University of Chicago Medicine, discusses the challenges providers face when navigating Medicare and Medicaid policy for administering chimeric antigen receptor (CAR) T-cell therapy as well as the future applications of cellular therapy.

Podcast Transcript:

How does Medicare and Medicaid policy make administering CAR-T therapy difficult for specific hospitals?

Dr Bishop: So, that is an interesting question because it is a bit different for Medicare and Medicaid. It can be difficult, yet not totally obstructionist, for us when the patient does not have supplemental insurance, as is often the case with Medicare. If a patient has supplemental insurance, it is more difficult for us than if the patient has private insurance. But we have still been able to secure the majority of patients.

Dealing with Medicaid can be even more difficult. It can be a prolonged process in which the review process can be hindered by scheduling conflicts and the individual state that Medicaid is coming from. The actual administration of the therapy can be prolonged because we cannot start any of the formal process of the CAR T-cell collection or manufacturing. We all know that lymphoma and leukemia do not wait around for papers to be signed. The review process can really slow down the process of administration for Medicaid patients. Overall, it is more difficult to get Medicaid patients approved than it is for Medicare patients.

What are some of the areas of educational needs for hospitals or institutions that are interested in providing CAR-T therapy to their patients?

Dr Bishop: I would like to believe that we have been a model for this at the University of Chicago. We went through extensive planning approximately 12 months before we anticipated commercialization of the first product. It takes quite a bit of organization from a clinical standpoint. We realized that having the foundation of a bone marrow transplant program is essential because a lot of the practices in administering CAR-T therapy are similar to that of a bone marrow transplant. There are other aspects that require additional planning—particularly in regard to the management of toxicities—and having a strong partnership with a medical intensive care unit and either a neuro-intensive care unit or a strong neurology program are essential.

In the bone marrow transplant setting, there are toxicities where a patient will go to an intensive care unit. For a toxicity like sepsis, there really isn’t too much difference in the way patients are treated if they had a bone marrow transplant or another procedure. On the other hand, cytokine release syndrome can come on very suddenly within just a few hours and you need to act appropriately. The way to manage cytokine release syndrome is different than almost anything that we have been accustomed to. With sepsis, you give lots of fluids. With cytokine release syndrome, if you give a lot of fluids, you could literally drown the patient because of leakage of fluid into the lungs. You need to have a ready and trained staff that includes nurses, physician assistants, and physicians who can identify those patients.

The neurotoxicities can come on even more suddenly. A patient with completely normal symptoms in the morning can become completely confused and deteriorate rapidly by 11:30 that same morning.

Hospitals needs to think about logistics – getting the patient in and having the capacity for doing more apheresis. Bone marrow transplant programs cannot get away with saying, “We are going to schedule this in an open spot two weeks from now.” Again, lymphoma and leukemia do not wait, so once you get a patient approved, you need have them move on to apheresis as soon as possible so you can ship the product off. The product cannot be generated until the lymphocytes are collected.

We have heard from other institutions the cases where apheresis was not immediately available. They would share that, “Our apheresis department is too busy and they will not have an open slot for five days,” whereas they need to plan for additional apheresis devices and hire additional apheresis nurses.

What are some of the necessary steps to ensuring that CAR-T therapies are accessible for broader patient populations?

Dr Bishop: I am not quite sure. One answer for sure is that patients have to fit the eligibility criteria, so that is what we look for. We evaluate every patient based upon many major criteria; however, the patient’s disease state is not necessarily a limiting thing. That’s a nice aspect of CAR T-cell therapy; we will not exclude a patient just because he or she has a large bulky disease or the disease is refractory to chemotherapy. The former might be the one predictor that we would to suggest a patient going to be more prone to develop a cytokine release syndrome and there is accumulating data to support it. But that does not mean they will not necessarily respond, so we do not exclude patients based on how much disease or what sites of disease they have.

Perhaps the largest consideration is that just because the disease may be refractory to prior therapy, that does not restrict them either. That actually has broadened this application because when a patient comes for a bone marrow transplant, especially for an autologous transplant, it is an absolute requirement that they have disease that is sensitive to chemotherapy. For allogeneic, it is a relative eligibility criterion that their disease is sensitive. The patients we see for CAR T cell therapy can have totally refractory disease.

There are other factors that go into it as well. Patients have to have decent organ function because they need the capability of getting through the cytokine release syndrome. While the overwhelming majority of patients get through it, they need to have good performance status.  Performance status is probably the key eligibility criteria that we look at; it seems to correlate with their ability to get through the potential complications.

Aside from hematologic malignancies for which CAR-T therapies have already been approved, what are some of the other disease states that you believe hold the most potential for these therapies?

Dr Bishop: First, it’s worth noting that for the hematologic malignancies, there will be further FDA expanded indications. We anticipate that the first commercial product for multiple myeloma may be approved by the end of the year or early next year. This indication will cover a large population.

My personal belief is that CAR T-cells will expand into solid tumors, though at a slow rate because that are a lot of obstacles for solid tumors. The major challenge with solid tumors is identifying good targets that are not expressed on normal tissues and having adequate potency of the CAR T-cells against that target. While CAR-T works very well against hematologic malignancies, the biology of solid tumors makes the cell therapy less effective, as of right now. Advancements in these tumors are all about finding good surface targets.

There can even be an expansion of CAR T-cells far beyond malignancies. We are just beginning to look at it in terms of treating autoimmune disease because the cells that mediate the problems associated with autoimmune disease are part of the immune system and you can actually use CAR T-cells to control the immune system. I recently came across some research involving CAR-T therapy to treat cardiovascular disease. There’s also some work being done in the solid organ transplantation space. Researchers are using CAR T-cells to control rejection, which I think has significant potential.

There is a paper that discusses cellular therapy being the third pillar of medicine behind traditional medicine and biologics. I believe that this will be the case because the possibilities are endless with cellular therapy. They can be used to deliver drugs and nanoparticles, as well as repair organs. This is a very exciting time, and the next 5-10 years will likely see an expansion of CAR T-cells, particularly in the solid tumor. There are a number of laboratories and pharmaceutical companies across the US that are investigating the fullest potential of CAR-T. One day, we may be able to reach the large majority of cancer patients with this therapy and for when there is a large unmet need—particularly for advanced metastatic disease—the opportunities and potential are unlimited.

For articles by First Report Managed Care, click here

To view the First Report Managed Care print issue, click here