Human herpesvirus 6B (HHV-6B) reactivation and disease are increasingly reported after chimeric antigen receptor (CAR) T-cell therapy (CARTx). HHV-6 reactivation in the CAR T-cell product was recently reported, raising questions about product and patient management. Because of overlapping manifestations with immune effector cell–associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging. We provide 2 lines of evidence assessing the incidence and outcomes of HHV-6B after CARTx. First, in a prospective study with weekly HHV-6B testing for up to 12 weeks after infusion, HHV-6B reactivation occurred in 8 of 89 participants; 3 had chromosomally integrated HHV-6 and were excluded, resulting in a cumulative incidence of HHV-6B reactivation of 6% (95% confidence interval [CI], 2.2-12.5). HHV-6B detection was low level (median peak, 435 copies per mL; interquartile range, 164-979) and did not require therapy. Second, we retrospectively analyzed HHV-6B detection in the blood and/or cerebrospinal fluid (CSF) within 12 weeks after infusion in CARTx recipients. Of 626 patients, 24 had symptom-driven plasma testing, with detection in 1. Among 34 patients with CSF HHV-6 testing, 1 patient had possible HHV-6 encephalitis for a cumulative incidence of 0.17% (95% CI, 0.02-0.94), although symptoms improved without treatment. Our data demonstrate that HHV-6B reactivation and disease are infrequent after CARTx. Routine HHV-6 monitoring is not warranted.

中文翻译：

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人类疱疹病毒 6 型再激活和疾病在嵌合抗原受体 T 细胞治疗接受者中并不常见


嵌合抗原受体 (CAR) T 细胞疗法 (CARTx) 后，人类疱疹病毒 6B (HHV-6B) 重新激活和疾病的报道越来越多。最近报道了 CAR T 细胞产品中的 HHV-6 重新激活，引发了有关产品和患者管理的问题。由于与免疫效应细胞相关神经毒性综合征的表现重叠，诊断 HHV-6B 脑炎具有挑战性。我们提供了 2 条证据来评估 CARTx 后 HHV-6B 的发生率和结果。首先，在一项前瞻性研究中，在输注后长达 12 周内每周进行 HHV-6B 测试，89 名参与者中有 8 名发生了 HHV-6B 重新激活； 3 号具有染色体整合的 HHV-6 并被排除，导致 HHV-6B 重新激活的累积发生率为 6%（95% 置信区间 [CI]，2.2-12.5）。 HHV-6B 检测水平较低（中位峰值，每毫升 435 个拷贝；四分位数范围，164-979），不需要治疗。其次，我们回顾性分析了 CARTx 接受者输注后 12 周内血液和/或脑脊液 (CSF) 中 HHV-6B 的检测情况。在 626 名患者中，24 名患者进行了症状驱动的血浆检测，其中 1 名检出。在 34 名接受 CSF HHV-6 检测的患者中，1 名患者可能患有 HHV-6 脑炎，累积发生率为 0.17%（95% CI，0.02-0.94） ），尽管症状无需治疗即可改善。我们的数据表明，CARTx 后 HHV-6B 重新激活和疾病很少见。不保证常规 HHV-6 监测。