Shang Qianwen, Xue Lian, Lu Aidong, Jia Yueping, Zuo YingXi, Zeng Huimin, Zhang Leping
Department of Pediatrics, Peking University People's Hospital, Peking University, Beijing, China.
Department of Pediatrics, Peking University People's Hospital, Peking University, Beijing, China.
Clin Lymphoma Myeloma Leuk. 2024 Jun;24(6):392-399.e5. doi: 10.1016/j.clml.2024.02.002. Epub 2024 Feb 7.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated significant efficacy in achieving complete remission (CR) in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, a considerable number of patients experience relapse within 1 year after CAR T-cell therapy, leading to an extremely poor prognosis, particularly in patients without bridging transplantation.
In our study, we investigated 42 children with R/R B-ALL who underwent anti-CD19 CAR T-cell therapy without bridging transplantation at our center. All patients were included in the response analysis and evaluated for survival and toxicity.
The cohort that received the CAR T-cell infusion exhibited a 100% CR rate by day 28 (d28). The overall survival (OS) at 4 years was 61.3% ± 8.5%, and the event-free survival (EFS) was 55.9% ± 7.9%, with a median follow-up duration of 50.1 months. Minimal residual disease (MRD) ≥1% was associated with inferior outcomes, resulting in lower 4-year OS (P = .033) and EFS (P = .014) compared to MRD<1%. The incidences of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity were 26.8% and 23.8%, respectively. Furthermore, MRD≥1% was identified as an independent factor associated with increased severity of CRS and occurrence of neurotoxicity.
These findings suggest that reducing the pre-infusion MRD could serve as an effective treatment strategy to enhance the outcomes of CAR T-cell therapy.
抗CD19嵌合抗原受体（CAR）T细胞疗法已证明在复发/难治性（R/R）B细胞急性淋巴细胞白血病（B-ALL）的儿科患者中实现完全缓解（CR）具有显著疗效。然而，相当数量的患者在CAR T细胞治疗后1年内复发，导致预后极差，尤其是在未进行桥接移植的患者中。
在我们的研究中，我们调查了42例在本中心接受抗CD19 CAR T细胞治疗且未进行桥接移植的R/R B-ALL儿童。所有患者均纳入缓解分析，并评估生存情况和毒性。
接受CAR T细胞输注的队列在第28天（d28）时CR率为100%。4年总生存率（OS）为61.3%±8.5%，无事件生存率（EFS）为55.9%±7.9%，中位随访时间为50.1个月。微小残留病（MRD）≥1%与较差的预后相关，与MRD<1%相比，4年OS（P = 0.033）和EFS（P = 0.014）更低。≥3级细胞因子释放综合征（CRS）和神经毒性的发生率分别为26.8%和23.8%。此外，MRD≥1%被确定为与CRS严重程度增加和神经毒性发生相关的独立因素。
这些发现表明，降低输注前MRD可作为提高CAR T细胞治疗疗效的有效治疗策略。
