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The Potential Impact of CAR T-Cell Treatment Delays on Society
Julia Thornton Snider, PhD; Michelle Brauer, BS; Rebecca Kee, BA; Katharine Batt, MD, MSc; Pinar Karaca-Mandic, PhD; Jie Zhang, PhD; and Dana P. Goldman, PhD
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The Potential Impact of CAR T-Cell Treatment Delays on Society

Julia Thornton Snider, PhD; Michelle Brauer, BS; Rebecca Kee, BA; Katharine Batt, MD, MSc; Pinar Karaca-Mandic, PhD; Jie Zhang, PhD; and Dana P. Goldman, PhD
Treatment delays limit the social value generated by chimeric antigen receptor (CAR) T-cell therapy for the treatment of pediatric acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
Further, the development of formal policies to cover CAR T has been slow. Currently, reimbursement is frequently done on an individual basis,12 with hospitals facing high financial risk to treat patients with CAR T without a guarantee of payment from insurers.35 Although larger health plans are often better equipped than smaller regional plans to handle such requests, reviewing each case individually lengthens the authorization process.12 In some cases, waiting for CAR T reimbursement approval may take up to 90 days, which may be longer than a patient’s survival.11 Some payers, such as Medicare, have had success securing coverage of CAR T in the outpatient setting12; however, challenges remain to provide sufficient reimbursement to hospitals to administer the treatment in an inpatient setting. Even with the recent approval of the new technology add-on payment of up to $186,500 per patient,36 intended to mitigate the additional costs of treatment, the reimbursement promised may fall short of the additional costs. When faced with high financial risk in the event that the costs of treating patients with CAR T exceed this payment cap, hospitals face disincentives for CAR T adoption. Thus, such policies may limit access for patients.

Additionally, CAR T is produced through a complex and individualized process37 that may be challenging to scale quickly. Efforts are currently under way to minimize delays caused by inefficiencies in production.38-40 Timely administration also necessitates that treatment centers be equipped with the proper equipment and human capital. Educating community oncologists is especially important in maximizing the efficacy and safety of CAR T, as patients are usually referred to their local oncologists for follow-up care after receiving treatment at the specified transplant centers.41 Professional organizations, such as the American Society of Hematology and the Foundation for the Accreditation of Cellular Therapy, are in the process of developing guidelines on CAR T.41,42

Our social value analysis indicates that facilitating timely patient access is a key consideration in determining an optimal financing approach. For patients with rapidly progressing cancer and high mortality rates,13,28 delaying treatment comes at a high cost. The case of CAR T provides a lesson to payers, policy makers, and innovators for incentivizing innovation and providing access to other curative therapies. In particular, therapies providing large QALY gains, such as curative therapies, bring large social value to society. Allowing innovators to share in that value incentivizes the development of future cures. However, stakeholders must work together to facilitate prompt patient access to such therapies. Efficient payment mechanisms, sufficient technological capabilities, adequate capital and human capital, and payment policy reform are required to minimize treatment delays for patients. Others have also argued that the price of CAR T should be lowered.43 These considerations are particularly important given other new or curative therapies in the pipeline, such as voretigene neparvovec-rzyl for mutation-associated retinal dystrophy,44 SPK-9001 for hemophilia,45 and LentiGlobin BB305 for sickle cell disease and beta-thalassemia.46

Limitations

Our study is based upon the overall experience of patients with pALL and DLBCL and does not account for heterogeneity in patient experiences. We excluded caregiver burden from this analysis, but a reduction could be expected using CAR T-cell therapies, as they may offer patients a possible remission with fewer treatments and adverse events. Additionally, our study examined the impact of treatment delays of various lengths in only the first cohort of patients. It is uncertain how treatment delays may change in the future. Because of a lack of clinical data, we were also unable to account in our analysis for potential reductions in CAR T efficacy due to treatment delays. To the extent that delayed treatment reduces CAR T efficacy, our estimates of the social value lost because of treatment delays are conservative.

Moreover, the total cost of treatment with CAR T is not yet clear20 and may change over time. The average total costs of tisagenlecleucel used in our analysis ($736,265; obtained from the ICER report10) included the average costs required by patients with pALL over the course of their treatment history (costs of CAR T, chemotherapy treatment, palliative chemotherapy, pretreatment, stem cell transplantation, adverse events, administration and monitoring, future healthcare, and end-of-life costs). This estimate substantially exceeded the average cost of treatment in the literature, which considered physician costs for leukapheresis and administration of lymphodepletion therapy, facilities, CAR T, drugs other than CAR T, facility fees for hospitalizations for cytokine release syndrome, and physician costs. These estimates ranged from $432,131 to $510,963 with the outcomes-based pricing arrangement.20

The average total cost of axicabtagene ciloleucel used in our analysis ($551,642) included costs accrued by patients over their treatment history (described above) and exceeded the $402,647 estimate reported by Hernandez et al in 2018.20

CONCLUSIONS

CAR T-cell therapies have the potential to provide significant benefit to patients with pALL and DLBCL and to society in the United States, particularly through gains in survival and productivity. However, the magnitude of benefit depends upon the ability of patients to access these treatments promptly.

Author Affiliations: Precision Health Economics (JTS, MB, RK, KB, DPG), Oakland, CA; Finance Department, Carlson School of Management, University of Minnesota (PK-M), Minneapolis, MN; Novartis Pharmaceuticals Corporation (JZ), East Hanover, NJ.

Source of Funding: Novartis.

Author Disclosures: Dr Thornton Snider is an employee of and holds equity in Precision Health Economics, which received payment from Novartis to conduct this research. Ms Brauer was employed by Precision Health Economics at the time that this research was conducted. Ms Kee is employed by Precision Health Economics. Dr Batt reports data interpretation for Novartis and consultancy for Precision Health Economics and has received honoraria from Novartis. Dr Karaca-Mandic provides consulting services to Precision Health Economics and received payment from Precision Health Economics for her involvement in the preparation of this manuscript. Dr Zhang is an employee of Novartis and owns Novartis stock. Dr Goldman served as a consultant to Precision Health Economics during the conduct of the study; owns equity (<1%) in Precision Health Economics’ parent company, Precision Medicine Group; has received payment from ACADIA Pharmaceuticals for service on a policy advisory board; was paid a fee for a lecture on cost-effectiveness at Amgen; and is the director of the Leonard D. Schaeffer Center for Health Policy & Economics, which is supported by gifts and grants from individuals, corporations, and associations; by government grants and contracts; and by private foundations (specific information about funding sources is available at healthpolicy.usc.edu).

Authorship Information: Concept and design (JTS, PK-M, JZ, DPG); acquisition of data (JTS, MB, RK, JZ); analysis and interpretation of data (JTS, MB, RK, KB, PK-M, JZ, DPG); drafting of the manuscript (JTS, MB, RK, KB, PK-M, JZ); critical revision of the manuscript for important intellectual content (JTS, MB, RK, KB, PK-M, JZ, DPG); statistical analysis (JTS, MB, RK); obtaining funding (JTS, DPG); administrative, technical, or logistic support (MB, RK); and supervision (JTS, KB, DPG).

Address Correspondence to: Rebecca Kee, BA, Precision Health Economics, 1999 Harrison St, Ste 1420, Oakland, CA 94612. Email: rebecca.kee@precisionxtract.com.
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