多发性骨髓瘤患者接受 ciltacabtagene autoleucel 后 CD4⁺ CAR-T 细胞强劲扩增与非 ICANS 神经毒性相关

Nonimmune effector cell-associated neurotoxicity syndrome neurotoxicities (NINTs) are serious, atypical toxicities associated with ciltacabtagene autoleucel (cilta-cel), a US Food and Drug Administration chimeric antigen receptor T cell (CAR T cell) therapy approved for relapsed/refractory multiple myeloma (RRMM). Risk factors contributing to the development of NINTs are poorly understood. In a cohort of 109 patients with RRMM treated with cilta-cel, 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 toward 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. Last, we characterize NINT-associated CD4 + CAR T cell populations, which are potential therapeutic targets for future exploration.