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Severe (grade\u2009\u2265\u20093) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade\u2009\u2265\u20093 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic\u00a0scoring systems (PSS) were derived, one for grade\u2009\u2265\u20093 CRS and one for grade\u2009\u2265\u20093 ICANS. CRS-PSS included bulky disease, a platelet count\u2009&lt;\u2009150\u00a0G\/L, a C-reactive protein (CRP) level\u2009&gt;\u200930\u00a0mg\/L and no bridging therapy or stable or progressive disease (SD\/PD) after bridging. Patients with a CRS-PSS score\u2009&gt;\u20092 had significantly higher risk to develop grade\u2009\u2265\u20093 CRS. ICANS-PSS included female sex, low level of platelets (&lt;\u2009150\u00a0G\/L), use of axi-cel and no bridging therapy or SD\/PD after bridging. Patients with a CRS-PSS score\u2009&gt;\u20092 had significantly higher risk to develop grade\u2009\u2265\u20093 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.<\/jats:p>","DOI":"10.1186\/s13045-024-01579-w","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T17:04:58Z","timestamp":1722963898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma"],"prefix":"10.1186","volume":"17","author":[{"given":"Pierre","family":"Sesques","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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Clin Lymphoma Myeloma Leuk. 2022;22(10):753\u20139.","journal-title":"Clin Lymphoma Myeloma Leuk"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-024-01579-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13045-024-01579-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-024-01579-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T07:05:44Z","timestamp":1726729544000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-024-01579-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1579"],"URL":"https:\/\/doi.org\/10.1186\/s13045-024-01579-w","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"assertion":[{"value":"6 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol was approved by national ethic committee and the data protection agency, and the study was undertaken in accordance with the Declaration of Helsinki. DESCAR-T is registered under the ClinicalTrials.gov identifier NCT04328298.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"P.S: Honoraria, Advisory\/Consultancy from Janssen, Roche, BMS, Chugai; Novartis and Kite\/Gilead; A.K: Honoraria from Kite\/Gilead; M.K: no conflict to declare; K.R. Kite\/Gilead: Research Funding and travel support; Novartis: Honoraria; BMS\/Celgene: Consultancy, Honoraria; Pierre-Fabre: travel support; MDJ: Consult\/advisor for Kite\/Gilead and Myeloid Therapeutics; research funding from Kite\/Gilead, Incyte, and Loxo@Lilly; R.DB: Honoraria, travel support, and membership of advisory boards from Novartis,Kite\/Gilead, Janssen, Pfizer, Celgene; G.B: Honoraria and travel fees from: Kite\/Gilead, BMS, Incyte, Novartis; FX.G: Honoraria: Kite\/Gilead, BMS, Milteny, Novartis.Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria; F.LB: Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Novartis: Honoraria; Celgene BMS: Research Funding; P.B. declares having received honoraria from Allogene, Amgen, BMS, Kit\/Gilead, Incyte, Jazz Pharmaceuticals, Miltenyi Biomedicine, Nektar Novartis and Pierre Fabre; MTR: No COIs; G.I:Honoraria and travel support: Novartis, Kite\/Gilead, Bristol-Myers Squibb, Abbvie, Autolus, Sandoz, Janssen, Miltenyi, AstraZeneca; MOR: no conflict to declare; ROC Honoraria for consultancy and advisory board:Roche, Takeda, BMS,MSD, Gilead\/Kite, Janssen, ADC Therapeutics, Incyte; Research funding: Roche,Gilead, Takeda; JO.B: no conflict to declare; M.M.: No COIs; M.J: no conflict to declare; J.A: No COIs; CCLl: Honoraria from Gilead\/Kite, Nektar Therapeutics; M.L: no conflict to declare; S.C: Kite\/gilead: Consultancy and Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees and Research Funding; Abbvie; Other: Travelfees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Other: travel fees and Research Funding; A.C.: No COIs; L. DDLR: No COIs; O.H: No COIs; S.G: No COIs; P.CM: COIs; P.F: No COIs; S.LG: Honoraria, travel support, and membership of advisory boards from Novartis, Kite\/Gilead, Janssen; F.M: Advisory boards pour Gilead, Novartis, BMS, \u00e9pizyme, miltenyi,Abbvie, genmab, Roche, AstraZeneca; Consultancy: gilead, roche; Scientific lectures:Roche, Chugai; T.G: honoraria from Gilead\/kite, Novartis, Takeda; G.C: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria; M.S. receives industry research support from Amgen, BMS\/Celgene, Gilead, Janssen, Miltenyi Biotec, Novartis, Roche, Seattle Genetics and Takeda and serves as a consultant\/advisor to AvenCell, CDR-Life, Ichnos Sciences, Incyte Biosciences, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Pfizer and Takeda. She serves on the speakers\u2019 bureau at Amgen, AstraZeneca, BMS\/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche and Takeda; P.B. declares having received honoraria from Novartis, Kite Gilead, BMS Celgene and Abbvie; F.L.L: has a scientific advisory role with Kite, a Gilead Company, Novartis, Celgene\/Bristol-Myers Squibb, GammaDelta Therapeutics, Wugen, Amgen, Calibr, and Allogene; is a consultant with grant options for Cellular Biomedicine Group, Inc.; and receives research support from Kite, a Gilead Company, Novartis, and Allogene; and reports that his institution holds unlicensed patents in his name in the field of cellular immunotherapy; R.S: No COIs; R.H: Honoraria from Bristol-Myers Squibb, Celgene, Gilead Sciences, Incyte, Janssen, Kite, MSD, Novartis and Roche; EB: Honoraria from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics; personal fees from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer; research funding paid to institution from Amgen, BMS.; P.S: Honoraria, Advisory\/Consultancy from Janssen, Roche, BMS, Chugai; Novartis and Kite\/Gilead A.K: Honoraria from Kite\/Gilead M.K: no conflict to declare K.R. Kite\/Gilead: Research Funding and travel support; Novartis: Honoraria; BMS\/Celgene: Consultancy, Honoraria; Pierre-Fabre: travel support MDJ: Consult\/advisor for Kite\/Gilead and Myeloid Therapeutics; research funding from Kite\/Gilead, Incyte, and Loxo@Lilly. R.DB: Honoraria, travel support, and membership of advisory boards from Novartis,Kite\/Gilead, Janssen, Pfizer, Celgene. G.B: Honoraria and travel fees from: Kite\/Gilead, BMS, Incyte, Novartis FX.G: Honoraria: Kite\/Gilead, BMS, Milteny, Novartis.Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. F.LB: Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Novartis: Honoraria; Celgene BMS: Research Funding. P.B. declares having received honoraria from Allogene, Amgen, BMS, Kit\/Gilead, Incyte, Jazz Pharmaceuticals, Miltenyi Biomedicine, Nektar Novartis and Pierre Fabre. MTR: No COIs. G.I:Honoraria and travel support: Novartis, Kite\/Gilead, Bristol-Myers Squibb, Abbvie, Autolus, Sandoz, Janssen, Miltenyi, AstraZeneca MOR: no conflict to declare ROC Honoraria for consultancy and advisory board:Roche, Takeda, BMS,MSD, Gilead\/Kite, Janssen, ADC Therapeutics, Incyte; Research funding: Roche,Gilead, Takeda JO.B: no conflict to declare M.M.: No COIs. M.J: no conflict to declare J.A: No COIs. CCLl: Honoraria from Gilead\/Kite, Nektar Therapeutics M.L: no conflict to declare S.C: Kite\/gilead: Consultancy and Membership on an entity's Board of Directors or advisory committees Astrazeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees and Research Funding; Abbvie; Other: Travelfees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Other: travel fees and Research Funding A.C.: No COIs. L. DDLR: No COIs. O.H: No COIs. S.G: No COIs. P.CM: COIs. P.F: No COIs. S.LG: Honoraria, travel support, and membership of advisory boards from Novartis, Kite\/Gilead, Janssen F.M: Advisory boards pour Gilead, Novartis, BMS, \u00e9pizyme, miltenyi,Abbvie, genmab, Roche, AstraZeneca; Consultancy: gilead, roche; Scientific lectures:Roche, Chugai T.G: honoraria from Gilead\/kite, Novartis, Takeda G.C: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. M.S. receives industry research support from Amgen, BMS\/Celgene, Gilead, Janssen, Miltenyi Biotec, Novartis, Roche, Seattle Genetics and Takeda and serves as a consultant\/advisor to AvenCell, CDR-Life, Ichnos Sciences, Incyte Biosciences, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Pfizer and Takeda. She serves on the speakers\u2019 bureau at Amgen, AstraZeneca, BMS\/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche and Takeda. P.B. declares having received honoraria from Novartis, Kite Gilead, BMS Celgene and Abbvie F.L.L: has a scientific advisory role with Kite, a Gilead Company, Novartis, Celgene\/Bristol-Myers Squibb, GammaDelta Therapeutics, Wugen, Amgen, Calibr, and Allogene; is a consultant with grant options for Cellular Biomedicine Group, Inc.; and receives research support from Kite, a Gilead Company, Novartis, and Allogene; and reports that his institution holds unlicensed patents in his name in the field of cellular immunotherapy. R.S: No COIs. R.H: Honoraria from Bristol-Myers Squibb, Celgene, Gilead Sciences, Incyte, Janssen, Kite, MSD, Novartis and Roche EB: Honoraria from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics; personal fees from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer; research funding paid to institution from Amgen, BMS.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"61"}}