PMID- 37486616 OWN - NLM STAT- MEDLINE DCOM- 20230919 LR - 20230924 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 7 IP - 18 DP - 2023 Sep 26 TI - A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials. PG - 5566-5578 LID - 10.1182/bloodadvances.2023009789 [doi] AB - The tremendous success of chimeric antigen receptor (CAR) T cells in children and young adults (CAYAs) with relapsed/refractory B-cell acute lymphoblastic leukemia is tempered by toxicities such as cytokine release syndrome (CRS). Despite expansive information about CRS, profiling of specific end-organ toxicities secondary to CAR T-cell therapy in CAYAs is limited. This retrospective, single-center study sought to characterize end-organ specific adverse events (AEs) experienced by CAYAs during the first 30 days after CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events were retrospectively analyzed for 134 patients enrolled in 1 of 3 phase 1 CAR T-cell trials (NCT01593696, NCT02315612, and NCT03448393), targeting CD19 and/or CD22. A total of 133 patients (99.3%) experienced at least 1 grade >/=3 (>/=Gr3) AE across 17 organ systems, of which 75 (4.4%) were considered dose- or treatment-limiting toxicities. Excluding cytopenias, 109 patients (81.3%) experienced a median of 3 >/=Gr3 noncytopenia (NC) AEs. The incidence of >/=Gr3 NC AEs was associated with the development and severity of CRS as well as preinfusion disease burden (>/= 25% marrow blasts). Although those with complete remission trended toward experiencing more >/=Gr3 NC AEs than nonresponders (median, 4 vs 3), nonresponders experiencing CRS (n = 17; 37.8%) had the highest degree of NC AEs across all patients (median, 7 vs 4 in responders experiencing CRS). Greater understanding of these toxicities and the ability to predict which patients may experience more toxicities is critical as the array of CAR T-cell therapies expand. This retrospective study was registered at www.clinicaltrials.gov as NCT03827343. CI - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - Silbert, Sara K AU - Silbert SK AUID- ORCID: 0000-0002-2746-9410 AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Madan, Sanna AU - Madan S AD - Center for Cancer Research, Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD. FAU - Holland, Elizabeth M AU - Holland EM AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Steinberg, Seth M AU - Steinberg SM AD - Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD. FAU - Little, Lauren AU - Little L AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Foley, Toni AU - Foley T AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Epstein, Monica AU - Epstein M AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Sarkisian, Angela AU - Sarkisian A AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Lee, Daniel W AU - Lee DW AUID- ORCID: 0000-0002-3249-9796 AD - Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA. FAU - Nikitina, Ekaterina AU - Nikitina E AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Kakumanu, Showri AU - Kakumanu S AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Ruppin, Eytan AU - Ruppin E AD - Center for Cancer Research, Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD. FAU - Shalabi, Haneen AU - Shalabi H AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Yates, Bonnie AU - Yates B AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. FAU - Shah, Nirali N AU - Shah NN AUID- ORCID: 0000-0002-8474-9080 AD - Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, MD. LA - eng SI - ClinicalTrials.gov/NCT03827343 SI - ClinicalTrials.gov/NCT01593696 SI - ClinicalTrials.gov/NCT02315612 SI - ClinicalTrials.gov/NCT03448393 GR - ZIA BC011823/ImNIH/Intramural NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 SB - IM MH - Young Adult MH - Humans MH - Child MH - T-Lymphocytes MH - Retrospective Studies MH - Immunotherapy, Adoptive/adverse effects MH - *Lymphoma, B-Cell MH - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy PMC - PMC10514106 COIS- Conflict-of-interest disclosure: N.N.S. receives royalties from CARGO Therapeutics. The remaining authors declare no competing financial interests. EDAT- 2023/07/24 13:06 MHDA- 2023/09/19 06:42 PMCR- 2023/07/26 CRDT- 2023/07/24 11:23 PHST- 2023/07/13 00:00 [accepted] PHST- 2023/01/19 00:00 [received] PHST- 2023/09/19 06:42 [medline] PHST- 2023/07/24 13:06 [pubmed] PHST- 2023/07/24 11:23 [entrez] PHST- 2023/07/26 00:00 [pmc-release] AID - 497016 [pii] AID - 10.1182/bloodadvances.2023009789 [doi] PST - ppublish SO - Blood Adv. 2023 Sep 26;7(18):5566-5578. doi: 10.1182/bloodadvances.2023009789.