Journal article
Cytokine release syndrome and neurotoxicity following CD19 CAR-T in B-cell lymphoma
Transplantation and cellular therapy, Vol.31(7), pp.419-433
07/2025
DOI: 10.1016/j.jtct.2025.03.011
PMCID: PMC12622908
PMID: 40288610
Abstract
•Immune effector cell-associated neurotoxicity syndrome (ICANS) rates remain stable•Cytokine release syndrome (CRS) and ICANS are strongly correlated•Severe forms of these toxicities are associated with reduced overall survival
Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns.
Analyze temporal trends, risk factors and associations between these toxicities and their severity.
In this registry study by the Center for International Blood and Marrow Transplant Research (CIBMTR), we studied CRS and ICANS in 1,916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival. Risk factors were assessed using Cox proportional hazards model.
Among patients developing CRS (75.2%), 11.3% had grade ≥ 3 CRS. Among patients developing ICANS (43.5%) 47.7% had grade ≥ 3 ICANS. Among patients developing CRS, severe CRS rates decreased from 14.0% in 2018 to 9.2% in 2020 (P< .01). However, the proportion of severe ICANS in patients who developed ICANS remained statistically unchanged (41.5% in 2018 to 53.7% in 2020, P= .10). CRS and ICANS were correlated: 57.1% of patients with CRS also experienced ICANS, and CRS was reported in 97.5% of ICANS cases, suggesting a potential continuum between toxicities. Axicabtagene ciloleucel was associated with higher risk of any grade CRS (OR, 4.6; 95% CI, 3.65-5.81) and ICANS (OR, 5.85; 95% CI, 4.48-7.64) as well as early and severe forms of both complications. Older age, lower performance status, and elevated lactate dehydrogenase (LDH) levels prior to infusion also variably predicted these toxicities. In a landmark analysis starting 30 days post-infusion, patients with severe CRS or severe ICANS had shorter overall survival compared to those without these toxicities.
High grades of CRS improved over time likely related to earlier intervention, development of ICANS is intrinsically related with CRS. These findings underscore the need for effective strategies to mitigate these toxicities and improve CAR-T safety.
Details
- Title: Subtitle
- Cytokine release syndrome and neurotoxicity following CD19 CAR-T in B-cell lymphoma
- Creators
- Roni Shouval - Memorial Sloan Kettering Cancer CenterChristopher Strouse - University of IowaSoyoung Kim - Medical College of WisconsinTemitope Oloyede - Medical College of WisconsinSairah Ahmed - The University of Texas MD Anderson Cancer CenterFarrukh T. Awan - The University of Texas Southwestern Medical CenterDanny Luan - Weill Cornell MedicineVeronika Bachanova - University of MinnesotaTalha Badar - Mayo ClinicMerav Bar - Bristol-Myers SquibbPere Barba - Universitat Autònoma de BarcelonaAmer M. Beitinjaneh - University of Miami HospitalAmanda Cashen - Washington University in St. Louis School of MedicineBhagirathbhai Dholaria - Vanderbilt University Medical CenterMahmoud Elsawy - Dalhousie UniversitySiddhartha Ganguly - Houston MethodistPraveen Ramakrishnan Geethakumari - The University of Texas Southwestern Medical CenterUri Greenbaum - Ben-Gurion University of the NegevHamza Hashmi - Memorial Sloan Kettering Cancer CenterLaQuisa C. Hill - Baylor College of MedicineMichael D. Jain - Moffitt Cancer CenterTania Jain - Johns Hopkins UniversityPartow Kebriaei - The University of Texas MD Anderson Cancer CenterAdam S Kittai - Icahn School of Medicine at Mount SinaiFrederick L. Locke - Moffitt Cancer CenterPremal D. Lulla - Baylor College of MedicineElena Mead - Memorial Sloan Kettering Cancer CenterJoseph P McGuirk - The University of Kansas Cancer CenterAlberto Mussetti - Institut Català d'OncologiaTaiga Nishihori - Moffitt Cancer CenterAmanda L. Olson - The University of Texas MD Anderson Cancer CenterMartina Pennisi - Fondazione IRCCS Istituto Nazionale dei TumoriMiguel-Angel Perales - Memorial Sloan Kettering Cancer CenterPeter A. Riedell - University of ChicagoWael Saber - Medical College of WisconsinAbu-Sayeef Mirza - Moffitt Cancer CenterMargarida Magalhaes-Silverman - University of IowaElizabeth J. Shpall - The University of Texas MD Anderson Cancer CenterMohamed Sorror - Fred Hutch Cancer CenterKitsada Wudhikarn - Chulalongkorn UniversityCameron J. Turtle - Fred Hutch Cancer CenterAmy Moskop - Medical College of WisconsinMarcelo C. Pasquini - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Transplantation and cellular therapy, Vol.31(7), pp.419-433
- DOI
- 10.1016/j.jtct.2025.03.011
- PMID
- 40288610
- PMCID
- PMC12622908
- NLM abbreviation
- Transplant Cell Ther
- ISSN
- 2666-6367
- eISSN
- 2666-6367
- Publisher
- Elsevier Inc; NEW YORK
- Grant note
- Cellular Therapy ConsortiumAdaptive Biotechnologies CorporationADC TherapeuticsAmgen, Inc.Astellas Pharma USAtara BiotherapeuticsBeiGenebluebird bio, inc.DBA Eurofins Transplant DiagnosticsIncyte CorporationJanssen Research & Development, LLCJazz Pharmaceuticals, Inc.Kiadis PharmaKiteGilead CompanyKyowa KirinLabcorpLegend BiotechMedac GmbHMerck Co.MesoblastTakeda Oncology Co.Miltenyi BiomedicineMiltenyi Biotec, Inc.Neovii Pharmaceuticals AGNovartis Pharmaceuticals CorporationOmeros CorporationPPD Development, LPRigel PharmaceuticalsSanofiStemline TechnologiesTakeda PharmaceuticalsTalaris TherapeuticsXenikos BVNIH/NCI: K08 CA282987, P30 CA0087480
Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Editas Medicine; Elevance Health; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Medac GmbH; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biomedicine; Miltenyi Biotec, Inc.; MorphoSys; MSA EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; OriGen Biomedical; Ossium Health, Inc.; Pfizer, Inc.; Pharmacyclics, LLC, An AbbVie Company; PPD Development, LP; REGiM-MUNE; Registry Partners; Rigel Pharmaceuticals; Sanofi; Sarah Cannon; Seagen Inc.; Sobi, Inc.; Stemcell Technologies; Stemline Technologies; STEMSOFT; Takeda Pharmaceuticals; Talaris Therapeutics; Vertex Pharmaceuticals; Vor Biopharma Inc.; Xenikos BV. Roni Shouval reports grant support from the NIH/NCI (K08 CA282987 and P30 CA0087480) .
- Language
- English
- Electronic publication date
- 04/25/2025
- Date published
- 07/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984815916602771
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