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优化高危复发/难治性 (r/r) DLBCL 的 CAR-T 细胞治疗真实世界结局:视频播客和病例示例

英文原题:Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) DLBCL with CAR T Cell Therapy: A Vodcast and Case Example.

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Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) DLBCL with CAR T Cell Therapy: A Vodcast and Case Example.

PubMed 2024/12/16(内容时间) Oncol Ther Q2 · IF 3.4(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法可有效治疗弥漫性大B细胞淋巴瘤(DLBCL),包括高级别疾病患者。但其安全性特征独特,包括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);充分管理这些事件对最大化治疗获益十分重要。本视频综述旨在介绍一名复发/难治性(r/r)DLBCL患者接受CAR-T 治疗的管理过程。2005年1月,该患者确诊为非典型慢性淋巴细胞白血病(CLL),接受两个周期氟达拉滨和环磷酰胺后,因皮肤毒性停药。2007年疾病进展,患者接受阿仑单抗治疗。2018年1月确诊DLBCL(非生发中心型,IV-A期,骨髓浸润);与既往CLL进行克隆性分析,结果阴性。

2018年3月,患者接受一线利妥昔单抗-环磷酰胺-阿霉素-长春新碱-泼尼松(R-CHOP)治疗6个周期,此时正电子发射断层扫描(PET)显示完全缓解。遗憾的是,2018年12月复发,开始二线利妥昔单抗、依托泊苷、阿糖胞苷、顺铂和泼尼松(R-ESHAP)治疗。2019年2月完成R-ESHAP第二周期后疾病进展,接受三线利妥昔单抗联合异环磷酰胺、吉西他滨、长春瑞滨和泼尼松(R-IGEV)4个周期。末次R-IGEV治疗于2019年5月完成,但患者仍进展。2019年7月,患者接受替沙格列赛输注。作者描述了CAR-T 疗法的疗效,以及如何管理患者发生的CRS和ICANS等不良事件。真实世界研究中替沙格列赛治疗DLBCL的结果与关键临床试验相似。

总之,CAR-T 疗法可有效治疗高危r/r DLBCL,并实现持久、长期缓解;但必须长期随访,以监测迟发不良事件和潜在淋巴瘤复发。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of patients with diffuse large B cell lymphoma (DLBCL), even those with high-grade disease.

However, it has a unique safety profile, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and robust management of these events are important to maximize benefits. The aim of this vodcast is to outline the management of a patient receiving CAR T-cell therapy for relapsed/refractory (r/r) DLBCL. In January 2005, the patient was diagnosed with atypical chronic lymphocytic leukemia (CLL) and treated with two cycles of fludarabine and cyclophosphamide before stopping due to skin toxicity. In 2007, the patient progressed and received alemtuzumab. In January 2018, the patient was diagnosed with DLBCL (nongerminal center, stage IV-A, bone marrow infiltration); a clonality analysis with the previous CLL provided a negative result. In March 2018, the patient received first-line treatment with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP)) for six cycles.

At this point, a positron emission tomography (PET) scan showed complete remission. Unfortunately, in December 2018, they experienced a relapse and second-line therapy with rituximab, etoposide, cytarabine, cisplatin, and prednisone (R-ESHAP) was started. Following the second cycle of R-ESHAP in February 2019, the patient progressed, and third-line treatment was provided by rituximab plus ifosfamide, gemcitabine, vinorelbine, and prednisone (R-IGEV) for four cycles.

The last cycle of R-IGEV was received in May 2019, but the patient progressed. In July 2019, the patient received a tisagenlecleucel infusion. The authors describe the effectiveness of the CAR T-cell therapy and how the adverse events (AEs) encountered, including CRS and ICANS, were managed. Results from real-world evidence studies of tisagenlecleucel in DLBCL are similar to those observed in the pivotal clinical trials.

In conclusion, CAR T-cell therapy can be effective and achieve long-lasting, durable responses in patients with high-risk r/r DLBCL.

However, long-term follow up is key to watch out for late AEs and potential lymphoma relapse.

论文信息

作者
Iacoboni G、Pérez Raya M
单位
Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain. giacoboni@vhio.net.Spain
期刊
Oncology and therapy2025 Mar
原文标识
PubMed 39680322 · DOI 10.1007/s40487-024-00319-x