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CRS 和 ICANS 对抗 CD19 CAR-T 治疗 B 细胞急性淋巴细胞白血病疗效的影响。

The influence of CRS and ICANS on the efficacy of anti-CD19 CAR-T treatment for B-cell acute lymphoblastic leukemia.

机构信息

Department of Hematology, Suqian First Hospital, Suqian, China.

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

出版信息

Front Immunol. 2024 Sep 27;15:1448709. doi: 10.3389/fimmu.2024.1448709. eCollection 2024.

Abstract

BACKGROUND

Chimeric antigen receptor T-cell (CAR-T) therapy has offered new opportunities for patients with relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common toxicities following CAR-T cell therapy. At present, whether the occurrence of CRS and ICANS will impact CAR-T activity remains unknown; this affects the therapeutic efficacy of CAR-T.

METHODS

In this multicenter retrospective study, we enrolled 93 patients with r/r B-ALL receiving anti-CD19 CAR-T cell therapy at four medical centers. We evaluated their complete response (CR) rates, minimal residual disease (MRD)-negative CR rates, and survival outcomes.

RESULTS

Among the included patients, 76 (81.7%) developed CRS and 16 (5.3%) developed ICANS. Fifteen patients experienced concurrent CRS and ICANS. However, no significant differences were noted in CR or MRD-negative CR rates between patients with and without CRS/ICANS. Furthermore, no significant difference was noted in leukemia-free survival (LFS) (p = 0.869 for CRS and p = 0.276 for ICANS) or overall survival (OS) (p = 0.677 for CRS and p = 0.326 for ICANS) between patients with and without CRS/ICANS. Similarly, patients with concurrent CRS and ICANS exhibited no differences in OS and LFS when compared with other patients. Multivariate analysis showed that the development of CRS and ICANS was not associated with any difference in OS and LFS.

CONCLUSION

Patients with CRS/ICANS experience similar clinical outcomes compared with those without CRS/ICANS following anti-CD19 CAR-T therapy.

摘要

背景

嵌合抗原受体 T 细胞(CAR-T)疗法为复发/难治性 B 细胞急性淋巴细胞白血病(r/r B-ALL)患者带来了新的机会。然而,细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)是 CAR-T 细胞治疗后最常见的两种毒性反应。目前,CRS 和 ICANS 的发生是否会影响 CAR-T 活性尚不清楚;这会影响 CAR-T 的治疗效果。

方法

在这项多中心回顾性研究中,我们纳入了在四家医疗中心接受抗 CD19 CAR-T 细胞治疗的 93 例 r/r B-ALL 患者。我们评估了他们的完全缓解(CR)率、微小残留病(MRD)阴性 CR 率和生存结局。

结果

在纳入的患者中,76 例(81.7%)发生 CRS,16 例(5.3%)发生 ICANS。15 例患者同时发生 CRS 和 ICANS。然而,有或无 CRS/ICANS 的患者的 CR 率或 MRD 阴性 CR 率无显著差异。此外,无 CRS 的患者的白血病无复发生存(LFS)(CRS 为 p=0.869,ICANS 为 p=0.276)或总生存(OS)(CRS 为 p=0.677,ICANS 为 p=0.326)与有 CRS 的患者无显著差异。同样,与其他患者相比,同时发生 CRS 和 ICANS 的患者的 OS 和 LFS 也无差异。多变量分析显示,CRS 和 ICANS 的发生与 OS 和 LFS 无差异无关。

结论

在接受抗 CD19 CAR-T 治疗后,有或无 CRS/ICANS 的患者的临床结局相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d16/11466746/48b5f8036af7/fimmu-15-1448709-g001.jpg

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