{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:56:47Z","timestamp":1793239007441,"version":"4.5.0"},"reference-count":28,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016058"],"award-info":[{"award-number":["P30 CA016058"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["K12CA133250"],"award-info":[{"award-number":["K12CA133250"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["KL2-TR002734"],"award-info":[{"award-number":["KL2-TR002734"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL127442-01A1"],"award-info":[{"award-number":["R01HL127442-01A1"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,7,9]]},"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Chimeric antigen receptor T-cell (CAR-T) infusion is associated with early toxicity. Yet, whether early toxicity development holds ramifications for long-term outcomes is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>From a large cohort of consecutive adult patients treated with CAR-T therapies for relapsed or refractory lymphomas from 2016 to 2019, we assessed progression-free survival (PFS), by toxicity development (cytokine release syndrome (CRS), neurotoxicity, or cardiotoxicity]. We also assessed the relationship of toxicity development to objective disease response, and overall survival (OS). Multivariable regression was utilized to evaluate relationships between standard clinical and laboratory measures and disease outcomes. Differences in outcomes, by toxicity status, were also assessed via 30-day landmark analysis. Furthermore, we assessed the effects of early anti-CRS toxicity therapy use (at \u2264grade 2 toxicity) on maximum toxicity grade observed, and long-term disease outcomes (PFS and OS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, from 102 CAR-T-treated patients, 90 were identified as treated with single-agent therapy, of which 88.9% developed toxicity (80 CRS, 41 neurotoxicity, and 17 cardiotoxicity), including 28.9% with high-grade (\u22653) events. The most common manifestations were hypotension at 96.6% and fever at 94.8%. Among patients with cardiac events, there was a non-significant trend toward a higher prevalence of concurrent or preceding high-grade (\u22653) CRS. 50.0% required tocilizumab or corticosteroids. The median time to toxicity was 3\u2009days; high grade CRS development was associated with cardiac and neurotoxicity. In multivariable regression, accounting for disease severity and traditional predictors of disease response, moderate (maximum grade 2) CRS development was associated with higher complete response at 1\u2009year (HR: 2.34; p=0.07), and longer PFS (HR: 0.41; p=0.02, in landmark analysis), and OS (HR: 0.43; p=0.03). Among those with CRS, relative blood pressure (HR: 2.25; p=0.004), respectively, also associated with improved PFS. There was no difference in disease outcomes, or maximum toxicity grade (CRS, neurotoxicity, or cardiotoxicity) observed, based on the presence or absence of the use of early CRS-directed therapies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among adult lymphoma patients, moderate toxicity manifest as grade 2 CRS after CAR-T infusion may associate with favorable clinical outcomes. Further studies are needed to confirm these findings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-002303","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T12:37:21Z","timestamp":1629808641000},"page":"e002303","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Early toxicity and clinical outcomes after chimeric antigen receptor T-cell (CAR-T) therapy for lymphoma"],"prefix":"10.1136","volume":"9","author":[{"given":"Jonathan E","family":"Brammer","sequence":"first","affiliation":[{"name":"Bone Marrow Transplantation and Cellular Therapies Program, Division of Hematology, The Ohio State University James Cancer Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-9943","authenticated-orcid":false,"given":"Zachary","family":"Braunstein","sequence":"additional","affiliation":[{"name":"Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aashish","family":"Katapadi","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Porter","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Biersmith","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avirup","family":"Guha","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"},{"name":"Cardiology, University Hospitals Harrington Heart & Vascular Institute, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumithira","family":"Vasu","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation and Cellular Therapies Program, Division of Hematology, The Ohio State University James Cancer Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedat O","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakima A","family":"Smith","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Buck","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Haddad","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, 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Transplantation and Cellular Therapies Program, Division of Hematology, The Ohio State University James Cancer Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Denlinger","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University James Cancer Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Vallakati","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragavendra","family":"Baliga","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Benza","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Binkley","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason","family":"Mocarski","sequence":"additional","affiliation":[{"name":"Internal Medicine, The Ohio State University Wexner Medical Center, 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FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. Available: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma [Accessed 30 Nov 2020]."},{"key":"2025100312084103000_9.8.e002303.9","unstructured":"U.S. National Library of Medicine . 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