medRxiv : the preprint server for health sciences · 2025
Robust CD4+ CAR T cell Expansion Is Associated with Non-ICANS Neurotoxicities Following Ciltacabtagene Autoleucel.
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Jurgens Eric M, Mitra Sneha, Herrera Kevin, Nemirovsky David, Bready Brenden, Derkach Andriy, Hosszu Kinga, McAvoy Devin, Firestone Ross S, Rajeeve Sridevi, Lesokhin Alexander M, Korde Neha, Tan Carlyn R, Hashmi Hamza, Hassoun Hani, Maclachlan Kylee, Shah Urvi A, Hultcrantz Malin, Merz Maximilian, Maura Francesco, Giralt Sergio A, Shah Gunjan, Landau Heather J, Scordo Michael, Santomasso Bianca D, Park Jae, Leslie Christina, Usmani Saad Z, Perica Karlo, Mailankody Sham
Аннотация
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+ CAR T cells rich in memory marker expression. We then identified CAR lymphocytosis associated CD4+ CAR T cell populations which exhibited increased inflammatory pathway gene expression. Finally, we characterize NINT associated CD4+ CAR T cell populations which are potential therapeutic targets for future exploration.