Editor’s note: Dr. Hudis hosts the ASCO in Action Podcast, which focuses on policy and practice issues affecting providers and patients. An excerpt of a recent episode is shared below; it has been edited for length and clarity. Listen to the full podcast online or through iTunes or Google Play.

I am really pleased to have Dr. Jason Westin as my guest. Dr. Westin is a member of the Association for Clinical Oncology’s Government Relations Committee and is the director of lymphoma clinical research in the Department of Lymphoma/Myeloma within the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center.

Dr. Westin is here to discuss chimeric antigen receptor, or CAR T-cell therapy. Two years ago, ASCO named CAR T-cell therapy as our Advance of the Year in our annual Clinical Cancer Advances report. CAR T is a groundbreaking and lifesaving treatment for children and young adults with acute lymphoblastic leukemia, and for adults with diffuse large B-cell lymphomas. But it comes with serious side effects, an extraordinary price tag, and a limited number of places—at least in the United States—where the treatment is currently available.

CH: What is CAR T-cell therapy for those who might not be familiar? And further, what makes it so potentially transformative in oncology?

JW: CAR T-cell therapy is an incredible breakthrough for our patients fighting cancer. This therapy takes a person’s T cells and infuses a new receptor on the outside, often a receptor that has an antibody fragment fused to parts of a T-cell receptor, and this allows the CAR T cell to recognize the cancer and fight it.

This has been potentially transformative because this therapy has completely different resistance mechanisms than standard chemotherapy and CAR T cells have shown incredible promise in clinical trials. The sky is the limit for how this could be used in the future by targeting other markers on different types of cancer, and opening up a whole new field of how we treat cancer, much in the way that immunotherapy with checkpoint antibodies has done over the past decade or so.

CH: Well, that's exciting, but you just hinted at what I think is the obvious next question. Breakthrough though this may be, for some patients this treatment has some significant side effects. Can you talk a little bit about what some of those side effects typically are, and how we hope to limit that in the future?

JW: CAR T-cell side effects are certainly unique and not overlapping in the way that we think of oncology therapy side effects. The CAR T-cell therapy side effects, in the short term, are broken down into two main camps.

The first is cytokine release syndrome (CRS). CRS is an overwhelming immune response where the new T cells that have been infused into the patient release an avalanche of cytokines to recruit other immune cells to help fight the cancer. In doing so, this induces a sepsis-like phenomenon of organ dysfunction, fever, and sometimes hypertension, which can be severe.

The second is a significant neurologic toxicity, immune effector cell-associated neurologic syndrome (ICANS). This can range from mild slowing of speech or cognition, all the way to status epilepticus, and anything in between. The most common troubles folks are having is mild slowing, aphasias, and/or seizures, which can be quite distressing to the patient and to the family.

Thankfully it seems that both CRS and ICANS appear to be fully reversible in most patients.

CH: There are several barriers right now to the therapy: we don't have applicability yet established for many diseases, there are special toxicities, and there is a geographic limitation. But beyond all of that, there's also a more conventional limitation, which is the cost.

As I understand it, the list price can range from $373,000 to treat an adult with an advanced lymphoma up to $475,000 to treat a pediatric indication. Further, I think these prices do not include the additional costs of hospitalization or managing side effects and other adverse events. Do these prices matter day to day in your practice? Do your patients need assistance navigating this?

JW: This is a major concern for us for the future of CAR T-cell therapy. It is a major cost for the one-time infusion of these T cells that are manufactured specifically for each given patient. Payers, including commercial, private, and now government payers, are supporting this. However, as the number of patients grow, this is going to increasingly strain the ability of the system to support an incredibly expensive therapy.

This is potentially home-run therapy for patients who may, in some cases, have decades of life left to live. The cost is not trivial for the benefit received, but it is an incredible amount put upon the system and the payers. Right now, through payers, it's doable, but I worry about the future of this as the number of patients who can benefit from this goes up.

CH: Last year, the Centers for Medicare and Medicaid Services (CMS) announced that Medicare would cover CAR T nationwide and we at ASCO were really delighted with that. But we recognize that, while the drugs are being reimbursed, that reimbursement remains at a level well below the actual acquisition costs. How is that shortfall impacting patients, and how is it addressed?

JW: It's different between different institutions and having the approval for this to be funded by CMS was great for our patients. However, the reimbursement, as you mentioned, that's proposed for that approval is quite low. It's not close to the price for the product or for the inpatient stay. Many hospitals are treating patients with commercial insurance with the idea that they are reimbursed at a higher level in order to cover patients who are treated and covered by government payer systems.

We've already seen some hospitals that are not able or willing to treat patients who are on a government health-care system, by sending them to larger systems that are treating many patients with commercial insurance to try and subsidize this net loss for a patient on Medicare or Medicaid. The substandard reimbursement is going to be a strain on the system in the long run.

CH: Well, that's interesting. Before the CMS coverage announcement came out, ASCO submitted comments to the agency, and this included our perspective on both appropriate coverage and reimbursement for CAR T, as well as an overarching description of ASCO's principles on approval coverage and getting the right treatment to the right patients at the right time.  

I mention that because I know you are familiar with policymaking in government, and we've been lucky to have you currently serving on the Government Relations Committee (GRC). From the perspective of the GRC, I wonder if you care to just expand a little bit on the importance of ASCO coming out and taking a stand on an issue like this.

JW: I think it's essential for organizations like ASCO to advocate on behalf of our patients by educating policymakers and lawmakers about exciting new breakthroughs. If we don't speak up for our patients, then our patients are going to suffer. And so, I applaud ASCO and the team that works on these recommendations and policy statements because it is essential for us to speak up.

This is the beginning of a new era of therapy for fighting cancer and we need to make sure that our policymakers and lawmakers are aware that this potentially transformative treatment is coming in order to create policy that allows patients dealing with cancer to have access to incredible new treatments.

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