{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:07:20Z","timestamp":1788358040454,"version":"build-2803163510"},"reference-count":43,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Chimeric antigen receptor (CAR) T cell therapies are approved as a third-line or later therapy for several hematological malignant neoplasms. Recently, randomized clinical trials have investigated their efficacy as a second-line treatment in high-risk relapsed or refractory diffuse large B-cell lymphoma (DLBCL) compared with salvage chemotherapy followed by hematopoietic stem cell transplantation (HSCT).<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the cost-effectiveness of axicabtagene ciloleucel and tisagenlecleucel vs standard care (SC) as second-line or later therapy for relapsed or refractory DLBCL, from both US health care sector and societal perspectives at a cost-effectiveness threshold of $150\u202f000 per quality-adjusted life-year (QALY).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This economic evaluation assessed cost-effectiveness using a partitioned survival model with 2021 US dollars and QALYs over a lifetime horizon. Model inputs were derived from 2 randomized clinical trials (ZUMA-7 and BELINDA) and published literature. In the trials, patients who did not respond to SC received CAR T cells (treatment switching or crossover), either outside the protocol (ZUMA-7) or as part of the protocol (BELINDA). A separate scenario analysis compared second-line axicabtagene ciloleucel with SC alone without treatment crossover to CAR T cell therapy. Data analysis was performed from December 18, 2021, to September 13, 2022.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n CAR T cell therapy (axicabtagene ciloleucel and tisagenlecleucel) compared with salvage chemotherapy followed by HSCT.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Costs and QALYs were used to derive incremental cost-effectiveness ratios (ICERs) for the health care sector and societal perspectives. Cost and QALYs were discounted at 3.0% annually. Univariate and multivariate probabilistic sensitivity analysis using 10\u202f000 Monte Carlo simulations were applied to test model uncertainty on the ICER.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Second-line axicabtagene ciloleucel was associated with an ICER of $99\u202f101 per QALY from the health care sector perspective and an ICER of $97\u202f977 per QALY from the societal perspective, while second-line tisagenlecleucel was dominated by SC (incremental costs of $37\u202f803 from the health care sector and $39 480 from the societal perspective with decremental QALY of -0.02). Third-line or later tisagenlecleucel was associated with an ICER of $126\u202f593 per QALY from the health care sector perspective and an ICER of $128\u202f012 per QALY from the societal perspective. Based on the scenario analysis of no treatment switching, second-line axicabtagene ciloleucel yielded an ICER of $216\u202f790 per QALY from the health care sector perspective and an ICER of $218\u202f907 per QALY from the societal perspective, compared with SC. When accounting for patients achieving prolonged progression-free survival who would not incur progression-related costs, in this scenario ICER changed to $125\u202f962 per QALY from the health care sector perspective and $122\u202f931 per QALY from the societal perspective. These results were most sensitive to increased list prices of CAR T cell therapy and QALY losses associated with axicabtagene ciloleucel and tisagenlecleucel.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n These findings suggest that second-line axicabtagene ciloleucel and third-line or later tisagenlecleucel were cost-effective in treating patients with relapsed or refractory DLBCL at the cost-effectiveness threshold of $150\u202f000 per QALY. However, uncertainty remains regarding the best candidates who would experience value gains from receiving CAR T cell therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.45956","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T11:01:47Z","timestamp":1671102107000},"page":"e2245956","source":"Crossref","is-referenced-by-count":42,"title":["Cost-effectiveness of Axicabtagene Ciloleucel and Tisagenlecleucel as Second-line or Later Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma"],"prefix":"10.1001","volume":"5","author":[{"given":"Jee H.","family":"Choe","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles"},{"name":"Leonard D. Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham","family":"Abdel-Azim","sequence":"additional","affiliation":[{"name":"Loma Linda University School of Medicine, Cancer Center, Children Hospital and Medical Center, Loma Linda, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William V.","family":"Padula","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles"},{"name":"Leonard D. Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abou-el-Enein","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles"},{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles"},{"name":"USC\/CHLA Cell Therapy Program, University of Southern California and Children\u2019s Hospital of Los Angeles, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"issue":"9","key":"zoi221300r1","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1038\/bjc.2015.94","article-title":"Lymphoma incidence, survival and prevalence 2004-2014: sub-type analyses from the UK\u2019s Haematological Malignancy Research Network.","volume":"112","author":"Smith","year":"2015","journal-title":"Br J Cancer"},{"issue":"27","key":"zoi221300r2","doi-asserted-by":"publisher","first-page":"4184","DOI":"10.1200\/JCO.2010.28.1618","article-title":"Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era.","volume":"28","author":"Gisselbrecht","year":"2010","journal-title":"J Clin Oncol"},{"issue":"16","key":"zoi221300r3","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1182\/blood-2017-03-769620","article-title":"Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study.","volume":"130","author":"Crump","year":"2017","journal-title":"Blood"},{"issue":"26","key":"zoi221300r4","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma.","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med"},{"issue":"1","key":"zoi221300r5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma.","volume":"380","author":"Schuster","year":"2019","journal-title":"N Engl J Med"},{"issue":"10254","key":"zoi221300r6","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet"},{"issue":"24","key":"zoi221300r8","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1200\/JCO.18.02079","article-title":"Cost effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma.","volume":"37","author":"Lin","year":"2019","journal-title":"J Clin Oncol"},{"issue":"12","key":"zoi221300r9","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1080\/13696998.2018.1529674","article-title":"Cost-effectiveness of axicabtagene ciloleucel for adult patients with relapsed or refractory large B-cell lymphoma in the United States.","volume":"21","author":"Roth","year":"2018","journal-title":"J Med Econ"},{"issue":"2","key":"zoi221300r11","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.0035","article-title":"Long-term survival and cost-effectiveness associated with axicabtagene ciloleucel vs chemotherapy for treatment of B-cell lymphoma.","volume":"2","author":"Whittington","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"7","key":"zoi221300r12","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1056\/NEJMoa2116133","article-title":"Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma.","volume":"386","author":"Locke","year":"2022","journal-title":"N Engl J Med"},{"issue":"7","key":"zoi221300r13","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa2116596","article-title":"Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma.","volume":"386","author":"Bishop","year":"2022","journal-title":"N Engl J Med"},{"issue":"10","key":"zoi221300r14","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/S1470-2045(21)00375-2","article-title":"Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study.","volume":"22","author":"Schuster","year":"2021","journal-title":"Lancet Oncol"},{"issue":"8","key":"zoi221300r16","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.clinthera.2021.06.011","article-title":"Cost-effectiveness analysis of tisagenlecleucel for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma in the United States.","volume":"43","author":"Qi","year":"2021","journal-title":"Clin Ther"},{"issue":"16","key":"zoi221300r17","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1182\/blood-2017-08-800730","article-title":"Lymphoma \u201cbenchmark\u201d or \u201cbench-smudge\u201d?","volume":"130","author":"Rutherford","year":"2017","journal-title":"Blood"},{"issue":"10","key":"zoi221300r20","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1200\/JCO.2013.51.5866","article-title":"Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.","volume":"32","author":"Maurer","year":"2014","journal-title":"J Clin Oncol"},{"issue":"9","key":"zoi221300r22","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1080\/13696998.2020.1769109","article-title":"Estimation of total costs in patients with relapsed or refractory diffuse large B-cell lymphoma receiving tisagenlecleucel from a US hospital\u2019s perspective.","volume":"23","author":"Yang","year":"2020","journal-title":"J Med Econ"},{"issue":"1","key":"zoi221300r23","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1080\/13696998.2021.1901721","article-title":"Cost effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the United States.","volume":"24","author":"Liu","year":"2021","journal-title":"J Med Econ"},{"issue":"8","key":"zoi221300r24","doi-asserted-by":"publisher","first-page":"4541","DOI":"10.1007\/s12325-021-01839-y","article-title":"Travel-related economic burden of chimeric antigen receptor T cell therapy administration by site of care.","volume":"38","author":"Snyder","year":"2021","journal-title":"Adv Ther"},{"issue":"7","key":"zoi221300r25","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1093\/jnci\/djy193","article-title":"Cost-effectiveness of chimeric antigen receptor T-cell therapy in pediatric relapsed\/refractory B-cell acute lymphoblastic leukemia.","volume":"111","author":"Sarkar","year":"2019","journal-title":"J Natl Cancer Inst"},{"issue":"5","key":"zoi221300r28","first-page":"192","article-title":"Economic burden of neurologic toxicities associated with treatment of patients with relapsed or refractory diffuse large B-cell lymphoma in the United States.","volume":"13","author":"Broder","year":"2020","journal-title":"Am Health Drug Benefits"},{"issue":"11","key":"zoi221300r31","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1002\/ajh.v95.11","article-title":"Commercial anti-CD19 CAR T cell therapy for patients with relapsed\/refractory aggressive B cell lymphoma in a European center.","volume":"95","author":"Sesques","year":"2020","journal-title":"Am J Hematol"},{"issue":"12","key":"zoi221300r32","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1080\/10428194.2018.1459613","article-title":"Costs of relapsed diffuse large B-cell lymphoma among Medicare patients.","volume":"59","author":"Huntington","year":"2018","journal-title":"Leuk Lymphoma"},{"issue":"31","key":"zoi221300r33","doi-asserted-by":"publisher","first-page":"3490","DOI":"10.1200\/JCO.2013.53.9593","article-title":"Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12.","volume":"32","author":"Crump","year":"2014","journal-title":"J Clin Oncol"},{"issue":"3","key":"zoi221300r34","doi-asserted-by":"publisher","first-page":"e355","DOI":"10.1200\/OP.20.00170","article-title":"Length of stay and hospital costs for patients undergoing allogeneic stem-cell transplantation.","volume":"17","author":"Godara","year":"2021","journal-title":"JCO Oncol Pract"},{"issue":"7","key":"zoi221300r35","first-page":"366","article-title":"The cost of hematopoietic stem-cell transplantation in the United States.","volume":"10","author":"Broder","year":"2017","journal-title":"Am Health Drug Benefits"},{"issue":"6","key":"zoi221300r36","doi-asserted-by":"publisher","first-page":"75s","DOI":"10.1200\/JOP.2011.000469","article-title":"Health care costs for patients with cancer at the end of life.","volume":"8","author":"Chastek","year":"2012","journal-title":"J Oncol Pract"},{"issue":"27","key":"zoi221300r37","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1200\/JCO.19.02104","article-title":"Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US Lymphoma CAR T Consortium.","volume":"38","author":"Nastoupil","year":"2020","journal-title":"J Clin Oncol"},{"key":"zoi221300r39","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.eclinm.2019.01.015","article-title":"Cell and gene therapy trials: are we facing an \u2018evidence crisis\u2019?","volume":"7","author":"Abou-El-Enein","year":"2019","journal-title":"EClinicalMedicine"},{"key":"zoi221300r40","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016747","article-title":"Cost effectiveness of second-line axicabtagene ciloleucel in relapsed refractory diffuse large B-cell lymphoma.","author":"Kambhampati","year":"2022","journal-title":"Blood"},{"issue":"11","key":"zoi221300r41","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.jtct.2022.08.010","article-title":"The cost-effectiveness of axicabtagene ciloleucel as second-line therapy in patients with large B-cell lymphoma in the United States: an economic evaluation of the ZUMA-7 trial.","volume":"28","author":"Perales","year":"2022","journal-title":"Transplant Cell Ther"},{"issue":"1","key":"zoi221300r42","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1080\/10428194.2021.1975188","article-title":"Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020-2025.","volume":"63","author":"Kanas","year":"2022","journal-title":"Leuk Lymphoma"},{"issue":"5","key":"zoi221300r43","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/s41571-022-00607-3","article-title":"Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion.","volume":"19","author":"Amini","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"zoi221300r15","author":"Locke"},{"key":"zoi221300r18","volume-title":"Cost-Effectiveness in Health and Medicine","author":"Neumann","year":"2017","edition":"Second ed"},{"key":"zoi221300r38","volume-title":"The EBMT\/EHA CAR-T Cell Handbook","author":"Abou-el-Enein","year":"2022"},{"key":"zoi221300r7","unstructured":"IBM. IBM Micromedex RED BOOK is now Merative Micromedex RED BOOK. Accessed June 6, 2022. https:\/\/www.ibm.com\/products\/micromedex-red-book."},{"key":"zoi221300r10","unstructured":"Institute for Clinical and Economic Review. Chimeric antigen receptor T-cell therapy for B-cell cancers: effectiveness and value. Accessed April 10, 2021. https:\/\/icer.org\/wp-content\/uploads\/2020\/10\/ICER_CAR_T_Final_Evidence_Report_032318.pdf"},{"key":"zoi221300r19","unstructured":"United States Department of Labor. Bureau of Labor Statistics, Consumer Price Index for all items in U.S. city average, all urban consumers, not seasonally adjusted. Accessed November 11, 2021. https:\/\/data.bls.gov\/cgi-bin\/surveymost?cu"},{"key":"zoi221300r21","unstructured":"Norwegian Medicine Agency (NoMA). Single technology assessment: tisagenlecleucel (Kymriah) for the treatment of second or later relapsed\/refractory diffuse large B cell lymphoma (DLBCL). Accessed August 18, 2021. https:\/\/legemiddelverket.no\/Documents\/Offentlig%20finansiering%20og%20pris\/Metodevurderinger\/K\/Kymriah_DLBCL_2019.pdf"},{"key":"zoi221300r26","unstructured":"Centers for Medicare and Medicaid Services. Medicare Part B October 2021 ASP pricing file. Accessed November 10, 2021. https:\/\/www.cms.gov\/medicare\/medicare-part-b-drug-average-sales-price\/2021-asp-drug-pricing-files"},{"key":"zoi221300r27","unstructured":"Centers for Medicare and Medicaid Services. Search the Physician Fee Schedule. Accessed November 10, 2021. https:\/\/www.cms.gov\/medicare\/physician-fee-schedule\/search"},{"key":"zoi221300r29","unstructured":"Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project free healthcare statistics. Accessed on November 29, 2021. https:\/\/hcupnet.ahrq.gov\/#setup"},{"key":"zoi221300r30","unstructured":"Centers for Medicare and Medicaid Services. Medicare Part D drug spending by drug. Accessed November 21, 2021. https:\/\/data.cms.gov\/summary-statistics-on-use-and-payments\/medicare-medicaid-spending-by-drug\/medicare-part-d-spending-by-drug"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2799582\/choe_2022_oi_221300_1670513524.0095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T11:01:57Z","timestamp":1671102117000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2799582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.45956","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}