{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:02:14Z","timestamp":1785506534811,"version":"3.56.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Novel therapies for 3L+ relapsed\/refractory (r\/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20\u2009\u00d7\u2009CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r\/r FL patients from a US third-party payer perspective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age \u226518) receiving 3L+ treatment for r\/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307\/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000\/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000\/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1393939","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T05:03:13Z","timestamp":1716526993000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States"],"prefix":"10.3389","volume":"15","author":[{"given":"Olalekan O.","family":"Oluwole","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markqayne D.","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Zur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl P.","family":"Ferrufino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Doble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik R.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Pinar","family":"Bilir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2015.1023712","article-title":"New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy","volume":"15","author":"Chihara","year":"2015","journal-title":"Expert Rev Anticancer Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24086","article-title":"Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: A longitudinal analysis of the National Cancer Data Base from 1998 to 2011","volume":"90","author":"Al-Hamadani","year":"2015","journal-title":"Am J Hematol"},{"key":"B3","unstructured":"Cancer Stat Facts: Non-Hodgkin Lymphoma2023"},{"key":"B4","volume-title":"SEER*Stat Database: Incidence - SEER Research Data","year":"2023"},{"key":"B5","volume-title":"Patient education: Follicular lymphoma in adults (Beyond the Basics)","author":"Freeman","year":"2023"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41408-020-00340-z","article-title":"Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups","volume":"10","author":"Batlevi","year":"2020","journal-title":"Blood Cancer J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15174403","article-title":"Burden of illness in follicular lymphoma with multiple lines of treatment, Italian RWE analysis","volume":"15","author":"Ferreri","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0138","article-title":"Follicular lymphoma: recent and emerging therapies, treatment strategies, and remaining unmet needs","volume":"24","author":"Matasar","year":"2019","journal-title":"Oncologist"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S368588","article-title":"Axicabtagene ciloleucel in the management of follicular lymphoma: current perspectives on clinical utility, patient selection and reported outcomes","volume":"15","author":"Mohty","year":"2023","journal-title":"Cancer Manag Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-3136","article-title":"Safety and efficacy of Axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed\/refractory large B-cell lymphoma","volume":"29","author":"Westin","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009260","article-title":"Mosunetuzumab monotherapy is active and tolerable in patients with relapsed\/refractory diffuse large B-cell lymphoma","volume":"7","author":"Bartlett","year":"2023","journal-title":"Blood Adv"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2023.09.007","article-title":"Indirect treatment comparisons of mosunetuzumab with third- and later-line treatments for relapsed\/refractory follicular lymphoma","volume":"24","author":"Bosch","year":"2024","journal-title":"Clin Lymphoma Myeloma Leukemia"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3164_386","article-title":"Matching-adjusted indirect comparison of axicabtagene ciloleucel versus mosunetuzumab in relapsed\/refractory follicular lymphoma patients after 2 prior systemic treatments","volume":"41","author":"Ray","year":"2023","journal-title":"Hematological Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00335-7","article-title":"Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study","volume":"23","author":"Budde","year":"2022","journal-title":"Lancet Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-174914","article-title":"Axicabtagene ciloleucel (Axi-cel) in patients with relapsed\/refractory indolent non-Hodgkin lymphoma: 4-year follow-up from the phase 2 ZUMA-5 trial","volume":"142","author":"Neelapu","year":"2023","journal-title":"Blood"},{"key":"B16","unstructured":"A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed\/\u200bRefractory Indolent Non-Hodgkin Lymphoma (ZUMA-5) (NCT03105336)2023"},{"key":"B17","unstructured":"A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL) (NCT02500407)2023"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/amajethics.2021.639","article-title":"How does cost-effectiveness analysis inform health care decisions","volume":"23","author":"Kim","year":"2021","journal-title":"AMA J Ethics"},{"key":"B19","unstructured":"2020-2023 Value Assessment Framework2020"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1405158","article-title":"Updating cost-effectiveness \u2014 The curious resilience of the $50,000-per-QALY threshold","volume":"371","author":"Neumann","year":"2014","journal-title":"New Engl J Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.7326\/M20-1392","article-title":"A health opportunity cost threshold for cost-effectiveness analysis in the United States","volume":"174","author":"Vanness","year":"2021","journal-title":"Ann Intern Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2021.722927","article-title":"An introduction to the main types of economic evaluations used for informing priority setting and resource allocation in healthcare: key features, uses, and limitations","volume":"9","author":"Turner","year":"2021","journal-title":"Front Public Health"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.12195","article-title":"Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine","volume":"316","author":"Sanders","year":"2016","journal-title":"JAMA"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jval.2021.11.1351","article-title":"Consolidated health economic evaluation reporting standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations","volume":"25","author":"Husereau","year":"2022","journal-title":"Value Health"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-136834","article-title":"Primary analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel (Axi-cel) in patients with relapsed\/refractory indolent non-hodgkin lymphoma (iNHL)","volume":"136","author":"Jacobson","year":"2020","journal-title":"Blood"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2030164","article-title":"Five-year outcomes for refractory B-cell lymphomas with CAR T-cell therapy","volume":"384","author":"Chong","year":"2021","journal-title":"N Engl J Med"},{"key":"B27","doi-asserted-by":"publisher","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"},{"key":"B28","volume-title":"HCUP Databases","year":"2023"},{"key":"B29","unstructured":"CPI-All Urban Consumers (Current Series)2023"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm543","article-title":"The impact of follicular lymphoma on health-related quality of life","volume":"19","author":"Pettengell","year":"2008","journal-title":"Ann Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"A294","DOI":"10.1016\/S1098-3015(10)63491-2","article-title":"PCN62 utility elicitation in patients with follicular lymphoma","volume":"6","author":"Wild","year":"2006","journal-title":"Value Health"},{"key":"B32","volume-title":"Hospital Outpatient Prospective Payment","year":"2023"},{"key":"B33","year":"2024"},{"key":"B34","unstructured":"Kite Pharma, Inc2024"},{"key":"B35","volume-title":"Medicare Physician Fee Schedule","year":"2023"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.12.114","article-title":"Resource utilization and factors prolonging hospitalization for patients with refractory and relapsed B-cell lymphoma receiving Axicabtagene ciloleucel (Axi-cel)","volume":"26","author":"Mian","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"key":"B37","article-title":"Cancer Hospitalizations for Adults, 2009. 2012 Feb","volume-title":"Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]","author":"Price","year":"2006"},{"key":"B38","volume-title":"Data on File","year":"2023"},{"key":"B39","unstructured":"2023 Q4 Medicare Laboratory Fee Schedule2023"},{"key":"B40","unstructured":"Lymphoma - Non-Hodgkin: Follow-Up Care"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2217\/fon.15.92","article-title":"Next-generation surveillance strategies for patients with lymphoma","volume":"11","author":"Cohen","year":"2015","journal-title":"Future Oncol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jnci\/djv280","article-title":"Hospice use among patients with lymphoma: impact of disease aggressiveness and curability","volume":"108","author":"Odejide","year":"2016","journal-title":"J Natl Cancer Inst"},{"key":"B43","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"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-182244","article-title":"Cost effectiveness of mosunetuzumab and CAR-T cell therapy in relapsed\/refractory follicular lymphoma","volume":"142","author":"Lin","year":"2023","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","first-page":"S153","DOI":"10.1016\/j.jval.2023.03.2493","article-title":"EE514 A cost-effectiveness analysis of mosunetuzumab for treatment of third- or higher-line relapsed or refractory (R\/R) follicular lymphoma (FL) in the United States (US)","volume":"26","author":"Matasar","year":"2023","journal-title":"Value Health"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.11.008","article-title":"Chimeric antigen receptor T-cell therapy in the outpatient setting: an expert panel opinion from the American society for transplantation and cellular therapy","volume":"30","author":"Oluwole","year":"2024","journal-title":"Transplant Cell Therapy Off Publ Am Soc Transplant Cell Ther"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-157473","article-title":"Chimeric antigen receptor T-cell therapy setting of care: A retrospective cohort analysis of MCL and FL patients in the US","volume":"140","author":"Seyedin","year":"2022","journal-title":"Blood"},{"key":"B48","volume-title":"ZUMA-5 Clinical Study Report. Data on File","year":"2023"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.7554","article-title":"Outpatient practice pattern and remote patient monitoring for axicabtagene ciloleucel CAR-T therapy in patients with aggressive lymphoma","volume":"39","author":"Bansal","year":"2021","journal-title":"J Clin Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1177\/0272989x17725740","article-title":"Methods for population-adjusted indirect comparisons in health technology appraisal","volume":"38","author":"Phillippo","year":"2018","journal-title":"Med Decis Making"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1393939\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T05:03:22Z","timestamp":1716527002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1393939\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,24]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2024.1393939"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1393939","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,24]]},"article-number":"1393939"}}