{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T08:44:10Z","timestamp":1794041050329,"version":"4.8.0"},"reference-count":26,"publisher":"American Society of Hematology","issue":"6","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,8]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed\/refractory (R\/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R\/R indolent non-Hodgkin lymphoma (iNHL; N\u00a0= 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R\/R iNHL after \u22652 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2\u00a0\u00d7 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n\u00a0= 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade \u22653 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R\/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023021243","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T20:01:14Z","timestamp":1698264074000},"page":"496-506","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":171,"title":["Three-year follow-up analysis of axicabtagene ciloleucel in relapsed\/refractory indolent non-Hodgkin lymphoma (ZUMA-5)"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1045-4914","authenticated-orcid":false,"given":"Sattva S.","family":"Neelapu","sequence":"first","affiliation":[{"name":"1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C.","family":"Chavez","sequence":"additional","affiliation":[{"name":"2Moffitt Cancer Center and Research Institute, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison R.","family":"Sehgal","sequence":"additional","affiliation":[{"name":"3University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8216-3457","authenticated-orcid":false,"given":"Narendranath","family":"Epperla","sequence":"additional","affiliation":[{"name":"4The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Ulrickson","sequence":"additional","affiliation":[{"name":"5Banner MD Anderson Cancer Center, Gilbert, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-7510","authenticated-orcid":false,"given":"Emmanuel","family":"Bachy","sequence":"additional","affiliation":[{"name":"6Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pashna N.","family":"Munshi","sequence":"additional","affiliation":[{"name":"7Georgetown Lombardi Comprehensive Cancer Center, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4998-9932","authenticated-orcid":false,"given":"Carla","family":"Casulo","sequence":"additional","affiliation":[{"name":"8Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Maloney","sequence":"additional","affiliation":[{"name":"9Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"de Vos","sequence":"additional","affiliation":[{"name":"10Ronald Reagan University of California Los Angeles Medical Center, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Reshef","sequence":"additional","affiliation":[{"name":"11Columbia University Herbert Irving Comprehensive Cancer Center, New York City, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Leslie","sequence":"additional","affiliation":[{"name":"12John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8525-9641","authenticated-orcid":false,"given":"Olalekan O.","family":"Oluwole","sequence":"additional","affiliation":[{"name":"13Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Yakoub-Agha","sequence":"additional","affiliation":[{"name":"14INSERM U1286, Infinite, Centre Hospitalier Universitaire de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Khanal","sequence":"additional","affiliation":[{"name":"15Fox Chase Cancer Center, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rosenblatt","sequence":"additional","affiliation":[{"name":"16University of Miami Sylvester Comprehensive Cancer Center, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-5749","authenticated-orcid":false,"given":"Ronald","family":"Korn","sequence":"additional","affiliation":[{"name":"17Imaging Endpoints, Scottsdale, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixin","family":"Peng","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Lui","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-922X","authenticated-orcid":false,"given":"Jacob","family":"Wulff","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhine","family":"Shen","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya","family":"Poddar","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Scott","family":"Jung","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Miao","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Beygi","sequence":"additional","affiliation":[{"name":"18Kite, a Gilead company, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"19Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"3","key":"2024020816242586800_bib1","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/ajh.25696","article-title":"Follicular lymphoma: 2020 update on diagnosis and management","volume":"95","author":"Freedman","year":"2020","journal-title":"Am J Hematol"},{"issue":"12","key":"2024020816242586800_bib2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11864-021-00909-1","article-title":"Novel therapies for follicular lymphoma and other indolent non-Hodgkin lymphomas","volume":"22","author":"Leslie","year":"2021","journal-title":"Curr Treat Options Oncol"},{"issue":"7","key":"2024020816242586800_bib3","doi-asserted-by":"crossref","first-page":"74","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"},{"issue":"4","key":"2024020816242586800_bib4","doi-asserted-by":"crossref","first-page":"e289","DOI":"10.1016\/S2352-3026(22)00033-3","article-title":"Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study","volume":"9","author":"Casulo","year":"2022","journal-title":"Lancet Haematol"},{"issue":"23","key":"2024020816242586800_bib5","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1200\/JCO.2014.59.7534","article-title":"Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare study","volume":"33","author":"Casulo","year":"2015","journal-title":"J\u00a0Clin Oncol"},{"key":"2024020816242586800_bib6","volume-title":"YESCARTA (axicabtagene ciloleucel). Prescribing information","year":"2022"},{"issue":"5","key":"2024020816242586800_bib7","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1172\/JCI46110","article-title":"CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients","volume":"121","author":"Savoldo","year":"2011","journal-title":"J\u00a0Clin Invest"},{"key":"2024020816242586800_bib8","volume-title":"YESCARTA (Axicabtagene Ciloleucel). Summary of product characteristics","year":"2022"},{"issue":"1","key":"2024020816242586800_bib9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1470-2045(21)00591-X","article-title":"Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial","volume":"23","author":"Jacobson","year":"2022","journal-title":"Lancet Oncol"},{"issue":"3","key":"2024020816242586800_bib10","doi-asserted-by":"crossref","first-page":"e838","DOI":"10.1097\/HS9.0000000000000838","article-title":"Survival by first-line treatment type and timing of progression among follicular lymphoma patients: a national population-based study in Sweden","volume":"7","author":"Weibull","year":"2023","journal-title":"Hemasphere"},{"issue":"27","key":"2024020816242586800_bib11","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification","volume":"32","author":"Cheson","year":"2014","journal-title":"J\u00a0Clin Oncol"},{"issue":"30","key":"2024020816242586800_bib12","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1200\/JCO.2016.66.9440","article-title":"Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: a pooled analysis of three multicenter studies","volume":"34","author":"Meignan","year":"2016","journal-title":"J\u00a0Clin Oncol"},{"issue":"13 suppl","key":"2024020816242586800_bib13","doi-asserted-by":"crossref","first-page":"CT036","DOI":"10.1158\/1538-7445.AM2021-CT036","article-title":"Axicabtagene ciloleucel (axi-cel) product attributes and immune biomarkers associated with clinical outcomes in patients with relapsed\/refractory indolent non-Hodgkin lymphoma in ZUMA-5","volume":"81","author":"Plaks","year":"2021","journal-title":"Cancer Res"},{"issue":"19","key":"2024020816242586800_bib14","first-page":"2307","article-title":"5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1)","volume":"141","author":"Neelapu","year":"2023","journal-title":"Blood"},{"issue":"8","key":"2024020816242586800_bib15","doi-asserted-by":"crossref","first-page":"1055","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"},{"issue":"2","key":"2024020816242586800_bib16","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/14737140.2023.2171994","article-title":"A\u00a024-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed\/refractory follicular lymphoma","volume":"23","author":"Palomba","year":"2023","journal-title":"Expert Rev Anticancer Ther"},{"issue":"2","key":"2024020816242586800_bib17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41591-021-01622-0","article-title":"Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial","volume":"28","author":"Fowler","year":"2022","journal-title":"Nat Med"},{"issue":"suppl 1","key":"2024020816242586800_bib18","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1182\/blood-2022-158024","article-title":"Long-term clinical outcomes and correlative efficacy analyses in patients (pts) with relapsed\/refractory follicular lymphoma (r\/r FL) treated with tisagenlecleucel in the ELARA trial [abstract]","volume":"140","author":"Dreyling","year":"2022","journal-title":"Blood"},{"issue":"31","key":"2024020816242586800_bib19","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1200\/JCO.19.01073","article-title":"Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study","volume":"37","author":"Bachy","year":"2019","journal-title":"J\u00a0Clin Oncol"},{"issue":"3","key":"2024020816242586800_bib20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41408-020-0299-0","article-title":"Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: a single-center experience","volume":"10","author":"Mozas","year":"2020","journal-title":"Blood Cancer J"},{"issue":"3","key":"2024020816242586800_bib21","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1200\/JCO.21.02370","article-title":"Three-year follow-up of KTE-X19 in patients with relapsed\/refractory mantle cell lymphoma, including high-risk subgroups, in the ZUMA-2 study","volume":"41","author":"Wang","year":"2023","journal-title":"J\u00a0Clin Oncol"},{"issue":"suppl 1","key":"2024020816242586800_bib22","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1182\/blood-2022-169783","article-title":"Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy [abstract]","volume":"140","author":"Iacoboni","year":"2022","journal-title":"Blood"},{"issue":"suppl 1","key":"2024020816242586800_bib23","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1182\/blood-2022-158492","article-title":"Association of metabolic tumor volume (MTV) and clinical outcomes in second-line (2L) relapsed\/refractory (R\/R) large B-cell lymphoma (LBCL) following axicabtagene ciloleucel (axi-cel) versus standard-of-care (SOC) therapy in ZUMA-7 [abstract]","volume":"140","author":"Locke","year":"2022","journal-title":"Blood"},{"key":"2024020816242586800_bib24","doi-asserted-by":"crossref","first-page":"713577","DOI":"10.3389\/fonc.2021.713577","article-title":"Tumor burden measured by 18F-FDG PET\/CT in predicting efficacy and adverse effects of chimeric antigen receptor T-cell therapy in non-Hodgkin lymphoma","volume":"11","author":"Hong","year":"2021","journal-title":"Front Oncol"},{"issue":"14","key":"2024020816242586800_bib25","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1182\/bloodadvances.2020001900","article-title":"High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma","volume":"4","author":"Dean","year":"2020","journal-title":"Blood Adv"},{"issue":"22","key":"2024020816242586800_bib26","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1182\/bloodadvances.2020003121","article-title":"Durable ibrutinib responses in relapsed\/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis","volume":"4","author":"Noy","year":"2020","journal-title":"Blood Adv"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2023021243\/2211231\/blood_bld-2023-021243-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2023021243\/2211231\/blood_bld-2023-021243-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T16:26:04Z","timestamp":1707409564000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/143\/6\/496\/498426\/Three-year-follow-up-analysis-of-axicabtagene"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,8]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,2,8]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023021243","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,8]]}}}