Cost-Effectiveness of KTE-X19 for Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in the United States

Bijal D Shah, Nathaniel J Smith, Chaoling Feng, Sushanth Jeyakumar, Jean-Gabriel Castaigne, Imi Faghmous, Behzad Kharabi Masouleh, Daniel C Malone, Michael R Bishop, Bijal D Shah, Nathaniel J Smith, Chaoling Feng, Sushanth Jeyakumar, Jean-Gabriel Castaigne, Imi Faghmous, Behzad Kharabi Masouleh, Daniel C Malone, Michael R Bishop

Abstract

Introduction: Despite currently available treatments for adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL), survival outcomes remain poor, highlighting the need for new therapeutic strategies. This study estimates the cost-effectiveness of KTE-X19 to treat adults with R/R ALL from a US payer perspective.

Methods: The model had two components: a decision-tree, where pre-infusion costs for patients who ultimately did not receive KTE-X19 are accounted for, followed by a partitioned survival analysis, where all KTE-X19 infused patients would enter the three-state (pre-progression, progressed disease, death) model. Comparators included current standard of care treatments, i.e., blinatumomab (BLIN), inotuzumab ozogamicin (INO), and salvage chemotherapy (CHEMO). Both standard parametric and mixture cure models were used to model survival. Efficacy, safety, healthcare resource utilization, and health state utility inputs were derived from the ZUMA-3 trial (NCT02614066) and literature. Cost inputs were derived from literature or publicly available sources. Outcomes and costs were discounted 3% annually. Results of KTE-X19 versus comparators are reported as total and incremental life-years (LYs), quality-adjusted life-years (QALYs), costs, and resulting incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses (PSA) and key scenario analyses were also performed.

Results: In the base case, incremental QALYs for KTE-X19 were 2.44, 3.26, and 4.61 versus BLIN, INO, and CHEMO, respectively. Incremental costs were $50,913, $251,532, and $432,027, respectively, resulting in ICERs of $20,843/QALY (versus BLIN), $77,271/QALY (versus INO), and $93,768/QALY (versus CHEMO). Deterministic sensitivity analysis results were most sensitive to subsequent allogeneic stem cell transplant rates and post-progression utilities. PSA found that KTE-X19 is 78.4%, 74.0%, and 75.4% likely to be cost-effective versus BLIN, INO, and CHEMO, respectively. Across most scenarios, at a willingness-to-pay (WTP) threshold of $150,000/QALY, KTE-X19 was cost-effective versus all treatments.

Conclusions: Compared to current options for adults with R/R ALL, KTE-X19 is cost-effective, driven primarily by improved survival.

Keywords: B-Cell; Brexucabtagene autoleucel; CD-19 antigens; Chimeric antigen receptor T-cell; Cost-effectiveness analysis; Economic evaluation; KTE-X19; Leukemia; Relapsed or refractory acute lymphoblastic leukemia.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Model structure
Fig. 2
Fig. 2
One-way sensitivity analysis results: KTE-X19 versus comparators
Fig. 2
Fig. 2
One-way sensitivity analysis results: KTE-X19 versus comparators

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590.
    1. Spoorendonk J, Feng C, Shah D, et al. PCN183 global incidence, prevalence, and survival in relapsed/refractory (R/R) adult acute lymphoblastic leukemia (aALL): a systematic literature review (SLR) Value Health. 2020;23:S455. doi: 10.1016/j.jval.2020.08.320.
    1. National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975–2018. In: Howlader N, Noone A, Krapcho M, et al., editors. SEER Cancer Statistics Review (CSR) 1975-2018. Bethesda, 2021.
    1. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125(14):2474–2487. doi: 10.1002/cncr.32116.
    1. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–847. doi: 10.1056/NEJMoa1609783.
    1. Samra B, Jabbour E, Ravandi F, et al. Evolving therapy of adult acute lymphoblastic leukemia: state-of-the-art treatment and future directions. J Hematol Oncol. 2020;13(1):70. doi: 10.1186/s13045-020-00905-2.
    1. Rowe JM. Prognostic factors in adult acute lymphoblastic leukaemia. Br J Haematol. 2010;150(4):389–405.
    1. Sarfati D, Koczwara B, Jackson C. The impact of comorbidity on cancer and its treatment. CA Cancer J Clin. 2016;66(4):337–350. doi: 10.3322/caac.21342.
    1. Zhu F, Wei G, Zhang M, et al. Factors associated with costs in chimeric antigen receptor T-cell therapy for patients with relapsed/refractory B-cell malignancies. Cell Transplant. 2020;29:963689720919434.
    1. Zhang X, Song X, Lopez-Gonzalez L, et al. Economic burden associated with adverse events of special interest in patients with relapsed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia in the United States. Expert Rev Pharmacoecon Outcomes Res. 2018;18(5):573–580. doi: 10.1080/14737167.2018.1490645.
    1. Cool C, Feng C, Wade S, et al. Healthcare resource utilization and costs in adult patients with relapsed or refractory acute lymphoblastic leukemia using real-world data from the United States. In: Pan Pacific Lymphoma Conference; Big Island, Hawaii 2021.
    1. Zhang X, Song X, Lopez-Gonzalez L, et al. Economic burden of veno-occlusive disease in patients with B-cell acute lymphoblastic leukemia in the United States. Clin Ther. 2018;40(10):1711–1719.e1. doi: 10.1016/j.clinthera.2018.08.005.
    1. Food and Drug Administration. TECARTUS: Highlights of prescribing information. 2021. .
    1. Shah BD, Ghobadi A, Oluwole OO, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. The Lancet. 2021;398(10299):491–502. doi: 10.1016/S0140-6736(21)01222-8.
    1. Brown PA, Shah B, Advani A, et al. Acute lymphoblastic leukemia, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2021;19(9):1079–1109. doi: 10.6004/jnccn.2021.0042.
    1. Gold MRSJ, Russell LB, Weinstein MC. Cost effectiveness in health and medicine. New York: Oxford University Press; 1996.
    1. Caro JJ, Briggs AH, Siebert U, et al. Modeling good research practices–overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1. Med Decis Making. 2012;32(5):667–677. doi: 10.1177/0272989X12454577.
    1. Institute for Clinical and Econoc Review. Chimeric Antigen Receptor T-Cell Therapy for B-Cell Cancers: Effectiveness and Value. Final Evidence Report. In: California Technology Assessment Forum, editor. 2018.
    1. Guyot P, Ades AE, Ouwens MJNM, et al. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12(1):9. doi: 10.1186/1471-2288-12-9.
    1. flexsurv. Flexible parametric survival and multi-state models. 2021.
    1. Lambert PC, Thompson JR, Weston CL, et al. Estimating and modeling the cure fraction in population-based cancer survival analysis. Biostatistics. 2007;8(3):576–594. doi: 10.1093/biostatistics/kxl030.
    1. Social Security Administration. Actuarial Life Table 2017. . Accessed 22 Apr 2021.
    1. Delea TE, Zhang X, Amdahl J, et al. Cost effectiveness of blinatumomab versus inotuzumab ozogamicin in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia in the United States. Pharmacoeconomics. 2019;37(9):1177–1193. doi: 10.1007/s40273-019-00812-6.
    1. Pulte ED, Vallejo J, Przepiorka D, et al. FDA supplemental approval: blinatumomab for treatment of relapsed and refractory precursor B-cell acute lymphoblastic leukemia. Oncologist. 2018;23(11):1366–1371. doi: 10.1634/theoncologist.2018-0179.
    1. NICE-National Institute for Health and Care Excellence. Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years. [TA554]. 2018. .
    1. Gökbuget N, Dombret H, Ribera J-M, et al. International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia. Haematologica. 2016;101(12):1524–1533. doi: 10.3324/haematol.2016.144311.
    1. Shah B, Faghmous I, Whitmore J, et al. The comparison of KTE-X19 to current standards of care: a pre-specified synthetic control study utilizing individual patient level data from historical clinical trials (SCHOLAR-3). In: American Society of Hematology: Annual Meeting & Exposition; December 11–14, 2021; Atlanta, Georgia2021.
    1. Stein A, Franklin JL, Chia VM, et al. Benefit-risk assessment of blinatumomab in the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Drug Saf. 2019;42(5):587–601. doi: 10.1007/s40264-018-0760-1.
    1. US Bureau of Labor Statistics. Consumer price index for medical care services. 2021. .
    1. KITE. A study evaluating brexucabtagene autoleucel (KTE-X19) in adult subjects with relapsed/refractory B-precursor acute lymphoblastic leukemia (ZUMA-3). In: Data on file, editor.
    1. IBM Micromedex RED BOOK. 2021. . Accessed 22 Apr 2021.
    1. KITE. Expert clinical opinion, data on file.
    1. CMS Laboratory Fee Schedule. 2021. Available from:
    1. CMS Physician Fee Schedule. 2021. . Accessed 22 Apr 2021.
    1. Chastek B, Harley C, Kallich J, et al. Health care costs for patients with cancer at the end of life. J Oncol Pract. 2012;8(6):75s–80s. doi: 10.1200/JOP.2011.000469.
    1. Sullivan PW, Slejko JF, Sculpher MJ, et al. Catalogue of EQ-5D scores for the United Kingdom. Med Decis Making. 2011;31(6):800–804. doi: 10.1177/0272989X11401031.
    1. Sung L, Buckstein R, Doyle JJ, et al. Treatment options for patients with acute myeloid leukemia with a matched sibling donor: a decision analysis. Cancer. 2003;97(3):592–600. doi: 10.1002/cncr.11098.
    1. Baumgardner JR, Brauer MS, Zhang J, et al. CAR-T therapy and historical trends in effectiveness and cost–effectiveness of oncology treatments. J Comp Effect Res. 2020;9(5):327–340. doi: 10.2217/cer-2019-0065.
    1. Sarkar RR, Gloude NJ, Schiff D, et al. Cost-effectiveness of chimeric antigen receptor T-Cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. J Natl Cancer Inst. 2019;111(7):719–726. doi: 10.1093/jnci/djy193.
    1. Simons CL, Malone D, Wang M, et al. Cost-effectiveness for KTE-X19 CAR T therapy for adult patients with relapsed/refractory mantle cell lymphoma in the United States. J Med Econ. 2021;24(1):421–431. doi: 10.1080/13696998.2021.1894158.
    1. 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(5):439–448. doi: 10.1056/NEJMoa1709866.
    1. Shah B, Smith N, Raad A, et al. ALL-190: cost-effectiveness of KTE-X19 for adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) in the United States. Clin Lymphoma Myeloma Leuk. 2021;21:S272–S273. doi: 10.1016/S2152-2650(21)01658-X.
    1. American Red Cross. Reimbursement Update. Available from: .

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