The ability to rewire human immune systems to fight cancer is certainly an exciting prospect. With the first 2 chimeric antigen receptor T-cell (CAR-T) therapies approved and over 200 more in clinical trials, expectations are high. But, as with any new treatment, consideration must be paid to the potential risks involved and the how they will be paid for. The promise of CAR-T therapies as a potential cure for cancers and the pressure that this creates in the market will likely serve to highlight the ineffective areas in our health care system, as providers contend with multiple barriers associated with the therapy.
Late in 2017, we witnessed the approval of 2 CAR-T cell products. CAR-Ts are genetically modified T cells, where a patient’s own T cells are manipulated ex vivo to recognize a specific antigen or protein on the malignant B-cell surface. The cells are infused back into the patient to elicit a very specific T-cell response against the malignant B cells.1 CAR-T cells have been studied most extensively in hematologic malignancies,2 confirmed by the approved indications for Kymriah (tisagenlecleucel)3 and Yescarta (axicabtagene ciloleucel),4 although there is ongoing work in solid tumors as well.5,6
While CAR-T therapy fills an unmet need in hematologic malignancies, they are not without risk. Side effects are substantial in certain patients and include the risk of cytokine release syndrome, presenting as fever, hypotension, altered mental status, and seizures, with some patients requiring intensive care.7 Both CAR-T cell products are monitored under the FDA Risk Evaluation and Mitigation Strategies (REMS) program.3,4
As with any new technology, our first concern will usually be cost. With the cost of Kymriah and Yescarta listed at $475,000 and $373,000 respectively,8 this is only the beginning. Additional costs will be incurred for the initial apheresis, followed by a round of chemotherapy for lymphodepletion and infusion of the CAR-T cells approximately 2 weeks later. In both cases, the CAR-T cells are infused in certified facilities where adequate training has been provided by the manufacturer. Patients and caregivers may need to travel great distances to certified facilities, and these travel costs could match the cost of the CAR-T therapy itself.
While the cost burden of treatment options is one that we will be continually battling and questioning, I would contend that the CAR-T therapy will highlight another disconnect in the health care system: patient care coordination and navigation.
Patient care coordination and navigation needs to go far beyond that of the physician-patient relationship. CAR-T therapy will require an active coordination between the physician, patient, and payer. While the physician-patient relationship remains intact, the payer needs to establish processes to become an active participant in the process. As noted, the CAR-T cells must be infused at a certified facility. That facility may or may not be within the payer’s immediate provider network. Medical necessity may not pose the biggest barrier to access this treatment option; rather, the reimbursement for the treatment process may prove to be the biggest barrier, especially to an out-of-network provider. The national payers will more than likely have national network coverage, however, there will be issues with the regional players. The certified facilities will probably have a set reimbursement level, which must be proposed and negotiated with the payer, and, under current processes today, the negotiation process can be very long and drawn out. Payers must be educated on the CAR-T treatment process and be timely in their responses in order to prevent treatment delays. It is most likely that in the appropriate case, services will not be denied, however, the reimbursement negotiation process must be completed prior to treatment commencing.
Along the line of certified facilities in the provider network, member benefit contracts will also need to be reviewed, and, in some cases, modified. In many benefits, patients will have a higher liability when using a non-network provider. Most health maintenance organization plans will not provide coverage for services received out-of-network. In cases where the patient has little choice as to where services can be accessed, the patient should not be penalized. Both CAR-T manufacturers have patient assistance programs in place to help with the patient’s higher liability, as well as travel logicstics.
These are exciting times where innovation is presenting us with new effective treatment options. As expected, these treatment options are costly. While we deal with cost burden issues on a daily basis, we now also need to focus our attention to the need to coordinate care and help the patient navigate through a complicated treatment process. Patient navigation is only starting to gain attention within the larger oncology practices. These practices represent a closed system with their patients. CAR-T therapy opens up the treatment process potentially to multiple providers and multiple facilities.
Are we up for the challenge to work together to allow the CAR-T therapy option to fulfill an unmet need?
1. National Cancer Institute. CAR T cells: engineering patients’ immune cells to treat their cancers. Cancer.gov website. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. Updated December 14, 2017. Accessed April 2, 2018.
2. Lederman L. CAR T-cell therapies for hematologic malignancies moving toward the clinic. Targeted Ther Oncol. http://www.targetedonc.com/publications/targeted-therapy-news/2017/august-2017/car-tcell-therapies-for-hematologic-malignancies-moving-toward-the-clinic. Published online August 2017. Accessed April 2, 2018.
3. Kymriah [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2017.
4. Yescarta [package insert]. Santa Monica, CA: Kite Pharma Inc.; 2017.
5. Xu J, Tian K, Zhang H, et al. Chimeric antigen receptor-T cell therapy for solid tumors require new clinical regimens. Expert rev Anticancer Ther. 2017;17(12):1099-1106.
6. Scarfò I, Maus MV. Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment. J ImmunoTher Cancer. 2017;5:28.
7. National Cancer Institute. Side effects of cancer treatment. Cancer.gov website. https://www.cancer.gov/about-cancer/treatment/side-effects. Updated September 22, 2017. Accessed April 2, 2018.
8. Clarke T, Berkrot B. FDA approves Gilead cancer gene therapy; price set at $373,000. Reuters. https://www.reuters.com/article/us-gilead-sciences-fda/fda-approves-gilead-cancer-gene-therapy-price-set-at-373000-idUSKBN1CN35H. Published October 18, 2017. Accessed April 2, 2018.