{"title":"嵌合抗原受体(CAR)T 细胞疗法在儿科患者中的应用:我们从哪里来,我们现在在哪里,我们将到哪里去?","authors":"Tristan Knight E, Olalekan Oluwole, Carrie Kitko","doi":"10.46989/001c.94386","DOIUrl":null,"url":null,"abstract":"CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). Somewhat uniquely among oncologic clinical trials, early clinical development occurred simultaneously in both children and adults. In subsequent years however, the larger number of adult patients with relapsed/refractory (r/r) malignancies has led to accelerated development of multiple CAR T-cell products that target a variety of malignancies, resulting in six currently FDA-approved for adult patients. By comparison, only a single CAR-T cell therapy is approved by the FDA for pediatric patients: tisagenlecleucel, which is approved for patients 25 years with refractory B-cell precursor ALL, or B-cell ALL in second or later relapse. Tisagenlecleucel is also under evaluation in pediatric patients with relapsed/refractory B-cell non-Hodgkin lymphoma, but is not yet been approved for this indication. All the other FDA-approved CD19-directed CAR-T cell therapies available for adult patients (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) are currently under investigations among children, with preliminary results available in some cases. As the volume and complexity of data continue to grow, so too does the necessity of rapid assimilation and implementation of those data. This is particularly true when considering “atypical” situations, e.g. those arising when patients do not precisely conform to the profile of those included in pivotal clinical trials, or when alternative treatment options (e.g. hematopoietic stem cell transplantation (HSCT) or bispecific T-cell engagers (BITEs)) are also available. We have therefore developed a relevant summary of the currently available literature pertaining to the use of CD19-directed CAR-T cell therapies in pediatric patients, and sought to provide guidance for clinicians seeking additional data about specific clinical situations.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":"44 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Implementation of Chimeric Antigen Receptor (CAR) T-cell Therapy in Pediatric Patients: Where Did We Come From, Where Are We Now, and Where are We Going?\",\"authors\":\"Tristan Knight E, Olalekan Oluwole, Carrie Kitko\",\"doi\":\"10.46989/001c.94386\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). 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All the other FDA-approved CD19-directed CAR-T cell therapies available for adult patients (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) are currently under investigations among children, with preliminary results available in some cases. As the volume and complexity of data continue to grow, so too does the necessity of rapid assimilation and implementation of those data. This is particularly true when considering “atypical” situations, e.g. those arising when patients do not precisely conform to the profile of those included in pivotal clinical trials, or when alternative treatment options (e.g. hematopoietic stem cell transplantation (HSCT) or bispecific T-cell engagers (BITEs)) are also available. 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引用次数: 0
摘要
CD19 定向嵌合抗原受体(CAR)T 细胞疗法彻底改变了 B 细胞急性淋巴细胞白血病(B-ALL)患者的治疗。早期的临床试验同时在儿童和成人中进行,这在肿瘤临床试验中略显独特。然而,在随后的几年里,由于复发/难治性(r/r)恶性肿瘤的成年患者人数增多,导致针对各种恶性肿瘤的多种 CAR T 细胞产品加速开发,目前已有六种产品获得 FDA 批准用于成年患者。相比之下,只有一种 CAR-T 细胞疗法获 FDA 批准用于儿童患者:tisagenlecleucel,该疗法获准用于 25 岁的难治性 B 细胞前体 ALL 或第二次或以后复发的 B 细胞 ALL 患者。Tisagenlecleucel也正在接受复发/难治性B细胞非霍奇金淋巴瘤儿科患者的评估,但尚未获准用于这一适应症。目前,美国食品及药物管理局批准的所有其他用于成人患者的 CD19 导向 CAR-T 细胞疗法(axicabtagene ciloleucel、brexucabtagene autoleucel 和 lisocabtagene maraleucel)都在儿童患者中进行研究,部分病例已取得初步结果。随着数据量和复杂性的不断增加,快速吸收和实施这些数据的必要性也在不断增加。在考虑 "非典型 "情况时尤其如此,例如,当患者与关键临床试验中的患者情况不完全一致时,或当有其他治疗方案(如造血干细胞移植(HSCT)或双特异性 T 细胞诱导剂(BITEs))可供选择时。因此,我们编写了一份关于在儿科患者中使用 CD19 导向 CAR-T 细胞疗法的现有文献的相关摘要,并试图为临床医生寻求有关特定临床情况的更多数据提供指导。
The Implementation of Chimeric Antigen Receptor (CAR) T-cell Therapy in Pediatric Patients: Where Did We Come From, Where Are We Now, and Where are We Going?
CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). Somewhat uniquely among oncologic clinical trials, early clinical development occurred simultaneously in both children and adults. In subsequent years however, the larger number of adult patients with relapsed/refractory (r/r) malignancies has led to accelerated development of multiple CAR T-cell products that target a variety of malignancies, resulting in six currently FDA-approved for adult patients. By comparison, only a single CAR-T cell therapy is approved by the FDA for pediatric patients: tisagenlecleucel, which is approved for patients 25 years with refractory B-cell precursor ALL, or B-cell ALL in second or later relapse. Tisagenlecleucel is also under evaluation in pediatric patients with relapsed/refractory B-cell non-Hodgkin lymphoma, but is not yet been approved for this indication. All the other FDA-approved CD19-directed CAR-T cell therapies available for adult patients (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) are currently under investigations among children, with preliminary results available in some cases. As the volume and complexity of data continue to grow, so too does the necessity of rapid assimilation and implementation of those data. This is particularly true when considering “atypical” situations, e.g. those arising when patients do not precisely conform to the profile of those included in pivotal clinical trials, or when alternative treatment options (e.g. hematopoietic stem cell transplantation (HSCT) or bispecific T-cell engagers (BITEs)) are also available. We have therefore developed a relevant summary of the currently available literature pertaining to the use of CD19-directed CAR-T cell therapies in pediatric patients, and sought to provide guidance for clinicians seeking additional data about specific clinical situations.