{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:26:59Z","timestamp":1782448019590,"version":"3.54.5"},"posted":{"date-parts":[[2025,10,30]]},"group-title":"Oncology","reference-count":86,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Non-ICANS neurotoxicities (NINTs) are serious, atypical toxicities associated with ciltacabtagene autoleucel, a commercial chimeric antigen receptor (CAR) T cell therapy approved for relapsed\/refractory multiple myeloma. Risk factors contributing to the development of NINTs are poorly understood. In a cohort of 109 patients, we identify predisposing risk factors and propose strategies to mitigate NINTs. We show that high peak absolute lymphocyte count is a strong NINT predictor which directly correlates with flow cytometry-based peripheral blood CAR T cell quantitation. The observed CAR lymphocytosis was polyclonal with a bias towards CD4\n                  <jats:sup>+<\/jats:sup>\n                  CAR T cells rich in memory marker expression. We then identified CAR lymphocytosis associated CD4\n                  <jats:sup>+<\/jats:sup>\n                  CAR T cell populations which exhibited increased inflammatory pathway gene expression. Finally, we characterize NINT associated CD4\n                  <jats:sup>+<\/jats:sup>\n                  CAR T cell populations which are potential therapeutic targets for future exploration.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>\n                    Ciltacabtagene autoleucel associated non-ICANS neurotoxicities are driven by high CD4\n                    <jats:sup>+<\/jats:sup>\n                    CAR T cell expansion exhibiting memory marker expression and upregulated inflammatory gene signaling pathways.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.28.25338924","type":"posted-content","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T21:10:38Z","timestamp":1761858638000},"source":"Crossref","is-referenced-by-count":2,"title":["Robust CD4\n                  <sup>+<\/sup>\n                  CAR T cell Expansion Is Associated with Non-ICANS Neurotoxicities Following Ciltacabtagene Autoleucel"],"prefix":"10.64898","author":[{"given":"Eric M.","family":"Jurgens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nemirovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenden","family":"Bready","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Derkach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Hosszu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"McAvoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross 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