These results support substantial net health benefits of tisagenlecleucel and axicabtagene ciloleucel compared with chemotherapy for DLBCL, which has demonstrated an associated response rate of 26% and 2-year overall survival rate of 20%.1 However, because of the limited amount of available evidence, uncertainties remain regarding the long-term health benefits and risk profile of CAR-T therapies, as well as the influence of these treatments on patients’ quality of life.
Although more costly compared with standard-of-care therapies, tisagenlecleucel has been linked to greater health gains in B-ALL, with cost-effectiveness ranging from $37,000 to $184,000 per quality-adjusted life year (QALY) gained across studies.1 Higher cost and greater QALY gains were also found for axicabtagene ciloleucel compared with chemotherapy for treatment of DLBCL, with cost-effectiveness estimates ranging from $58,000 to $289,000 per QALY gained; for tisagenlecleucel for treatment of DLBCL, cost-effectiveness estimates ranged from $168,000 to $223,000 per QALY gained.
“The wide range in cost-effectiveness observed for each CAR-T therapy is largely driven by the uncertainty in survival and the duration of response” due to a lack of long-term data, wrote Whittington and colleagues.1 Evidence pertaining to cost-effectiveness will likely become more precise as “additional clinical evidence becomes available and as CAR-T therapy becomes more common in the actual care setting outside of a controlled study environment.”
In value assessments of tisagenlecleucel for ALL and axicabtagene ciloleucel for DLBCL, the Institute for Clinical and Economic Review (ICER) determined that the clinical evidence provides “moderate certainty of a small or substantial net health benefit, with high certainty of at least a small net health benefit.”1 For these indications as well as for tisagenlecleucel for DLBCL, the National Institute for Health and Care Excellence (NICE) reported that the clinical evidence indicates “clinically meaningful overall and progression-free survival,” although uncertainty remains due to limited evidence.
Paying for CAR-T Therapy
Payment schemes depend on the payer type and setting in which CAR-T therapy is administered. A national coverage decision finalized by the Centers for Medicare and Medicaid Services (CMS) in August 2019 “suggests CAR-T will be covered for FDA-approved CAR-T [therapies] administered at health care facilities enrolled in the FDA risk evaluation and mitigation strategies for either FDA-approved indications or indications supported in one or more CMS-approved compendia.”1
Although this decision is expected to incentivize CAR-T access, full coverage is not guaranteed, and it appears that the policy could result in steep losses (up to $200,000 per infusion) for hospitals that administer CAR-T. Meanwhile, outpatient infusions could potentially result in significant financial barriers for patients while overcompensating providers and facilities.
The CAR-T payment structure is less clear for commercial payers, who “are still working out arrangements with hospitals and centers of excellence with no common path toward approval and payment.”1
To address affordability concerns, a range of alternative payment mechanisms have been proposed, including credit mechanisms in which payers could make installment payments with interest to the manufacturer, outcome-based contracts involving shared risk between payers and manufacturers, bundled payment schemes, insurance or reinsurance for payers, and managed entry or price-volume agreements involving rebates from manufacturers.1
With an increasing number of CAR-T therapies under development, there is a need for research that is “focused on actionable solutions that motivate payers, manufacturers, providers, hospitals, and patients to work together,” the researchers concluded.1 “Publicly funded and actionable research into novel fair value payment mechanisms and value assessment frameworks that incentivize stakeholder cooperation are solutions to break through the status quo.”
1. Whittington MD, McQueen RB, Campbell JD. Valuing chimeric antigen receptor T-cell therapy: current evidence, uncertainties, and payment implications [published online December 5, 2019]. J Clin Oncol. doi:10.1200/JCO.19.01558
2. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439-448.
3. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20:31-42.
4. Schuster SJ, Bishop MR, Tam CS, et al; JULIET investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56.