Estimation of Total Costs in Pediatric and Young Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia Receiving Tisagenlecleucel from a US Hospital's Perspective

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a hematological malignancy that primarily affects children, adolescents, and young adults. Patients with refractory disease or in second or later relapse have a poor prognosis and are less likely to achieve long-term disease remission. In August 2017, tisagenlecleucel, a Chimeric antigen receptor T-cell (CAR-T) therapy, received approval from the US Food and Drug Administration (FDA) for the treatment of pediatric and young adult patients with B-cell ALL that is refractory or in second or later relapse based on data from the pivotal Phase II trial ELIANA. Since the launch of tisagenlecleucel in ALL, there has been discussion on the expected health resource use (HRU) and costs associated with the treatment beyond the cost of the drug and procedure. The current study aimed to estimate the total costs of tisagenlecleucel for the treatment of pediatric and young adult patients with relapsed or refractory (r/r) ALL from a US hospital's perspective using the HRU and safety data from the ELIANA trial.

METHODS: An economic model was developed to assess the total costs associated with tisagenlecleucel treatment among pediatric and young patients with r/r ALL from a US hospital's perspective. The total costs were estimated from the time of leukapheresis to 2 months post-infusion, which is the timeframe when HRU related to the tisagenlecleucel infusion would likely occur. The model was developed using a fee-for-service approach, which estimated costs based on the HRU and safety data from the ELIANA trial. The model considered costs of leukapheresis, lymphodepleting chemotherapy, tisagenlecleucel infusion and hospital administration, inpatient and intensive care unit (ICU) admission, medical professional visits, lab tests and procedures, and additional medication and HRU for the management of major adverse events (AEs) (e.g., cytokine release syndrome [CRS]). Medication costs were estimated using the wholesale acquisition cost from the Truven Redbook. Unit costs for medication administration, medical professional visits, and lab test and procedures were obtained from the Centers for Medicare & Medicaid Services Physician Fee Schedule. Unit costs for AE were derived from the Healthcare Cost and Utilization Project. The daily inpatient and ICU costs were obtained from the literature. All costs were inflation-adjusted to 2019 USD. The base-case model estimated the total costs using the observed hospitalization, ICU and AE data from all patients receiving tisagenlecleucel infusion in the ELIANA trial. Scenario analyses were conducted varying key assumptions related to AEs and hospitalization.

RESULTS: The overall costs associated with the tisagenlecleucel treatment from leukapheresis to 2-months post infusion in r/r ALL patients were estimated at $612,779. Considering a list price of tisagenlecleucel at $475,000, the model calculated additional cost of care to be $137,636, which included $70,968 (51.5%) for AE management, $57,952 (42.1%) for inpatient and ICU not attributing to AEs, $5,209 (3.8%) for lab tests and procedures, $1,780 (1.3%) for medical professional visits, and $1,727 (1.3%) for lymphodepleting drug and administration. In the sensitivity analyses, the total costs ranged from $483,169 (no AEs, no hospitalization) to $672,373 (CRS and other AEs, hospitalization).

CONCLUSIONS: This is the first US-focused study that comprehensively evaluated the cost associated with tisagenlecleucel treatment based on HRU data from clinical trial observation. The total costs within 2 months of tisagenlecleucel administration was estimated at $612,779, on average. Compared to the cost of tisagenlecleucel procedure, the non-drug cost is relatively small. Further research with estimates based on real-world clinical use of tisagenlecleucel is warranted.