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Original Investigation
December 2018

Long-term Survival and Value of Chimeric Antigen Receptor T-Cell Therapy for Pediatric Patients With Relapsed or Refractory Leukemia

Author Affiliations
  • 1Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus, Aurora
  • 2The Institute for Clinical and Economic Review, Boston, Massachusetts
  • 3Department of Medicine, University of California, San Francisco
JAMA Pediatr. 2018;172(12):1161-1168. doi:10.1001/jamapediatrics.2018.2530
Key Points

Question  What is the long-term survival and value of tisagenlecleucel for pediatric patients with relapsed or refractory leukemia?

Findings  In this decision-analytic modeling study using deidentified data, cost-effectiveness analysis generated an incremental cost-effectiveness ratio between $37 000 and $78 000 per quality-adjusted life-year gained over a patient lifetime horizon, with more than 40% of those initiating tisagenlecleucel treatment becoming long-term survivors.

Meaning  Tisagenlecleucel seems to be priced in alignment with its clinical benefits, although its value depends on assumptions around long-term survival.


Importance  Among children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia, the rate of 5-year disease-free survival is 10% to 20%. Approval of tisagenlecleucel, a chimeric antigen receptor T-cell therapy, represents a new and potentially curative treatment option. However, tisagenlecleucel is expensive, with a current list price of $475 000 per one-time administration.

Objective  To estimate the long-term survival and value of tisagenlecleucel for children and young adults with B-cell acute lymphoblastic leukemia.

Design, Setting, and Participants  In this cost-effectiveness analysis, a decision analytic model was designed to extrapolate trial evidence to a patient lifetime horizon. The survival evidence for the model was extracted from 3 studies: B2202 (enrolled patients from April 8, 2015, to November 23, 2016), B2205J (enrolled patients from August 14, 2014, to February 1, 2016), and B2101J (enrolled patients from March 15, 2012, to November 30, 2015). Long-term survival and outcomes of patients younger than 25 years with B-cell acute lymphoblastic leukemia that is refractory or in second or later relapse were derived using flexible parametric modeling from the direct extrapolation of event-free survival and overall survival curves. The published Kaplan-Meier curves were digitized from November 1, 2017, to November 30, 2017, using an algorithm to impute patient-level time-to-event data. Sensitivity and scenario analyses assessed uncertainty in the evidence and model assumptions to further bound the range of cost-effectiveness. Data were analyzed from December 1, 2017, to March 31, 2018.

Interventions  The primary intervention of interest was tisagenlecleucel. The comparator of interest was the chemoimmunotherapeutic agent clofarabine.

Main Outcomes and Measures  Model outcomes included life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained.

Results  Forty percent of patients initiating treatment with tisagenlecleucel are expected to be long-term survivors, or alive and responding to treatment after 5 years. Tisagenlecleucel had a total discounted cost of $667 000, with discounted life-years gained of 10.34 years and 9.28 QALYs gained. The clofarabine comparator had a total discounted cost of approximately $337 000, with discounted life-years gained of 2.43 years and 2.10 QALYs gained. This difference resulted in an incremental cost-effectiveness ratio of approximately $42 000 per life-year gained and approximately $46 000 per QALY gained for tisagenlecleucel vs clofarabine. These results were robust to probabilistic sensitivity analyses. Across scenario analyses that included more conservative assumptions regarding long-term relapse and survival, the incremental cost-effectiveness ratio ranged from $37 000 to $78 000 per QALY gained.

Conclusions and Relevance  Tisagenlecleucel likely provides gains in survival and seems to be priced in alignment with these benefits. This study suggests that payers and innovators should develop novel payment models that reduce the risk and uncertainty around long-term value and provide safeguards to ensure high-value care.