决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell Lymphoma.
弥漫大 B 细胞淋巴瘤(DLBCL)是一种侵袭性恶性肿瘤,传统上采用以蒽环类药物为基础的化疗,但约三分之一的患者在一线治疗后复发或存在原发难治。
弥漫性大B细胞淋巴瘤(DLBCL)是一种侵袭性恶性肿瘤,传统上采用蒽环类药物为基础的化疗;约三分之一患者在一线治疗后复发或呈原发难治。本综述重点介绍美国食品药品监督管理局(FDA)批准用于复发/难治(R/R)DLBCL的7种新型药物,其中包括5种靶向CD19的疗法,3种为嵌合抗原受体(CAR)T细胞疗法。文章还介绍新型非细胞靶向疗法,并根据治疗目标讨论最佳用药顺序,尤其强调以治愈为目标时CAR-T细胞疗法的作用。作者评估部分新药耐受性有限的问题、老年患者的治疗前景及相关经济负担,并依据关键临床试验总结各类靶向治疗的优势和局限。最后,综述正在进行的、具有前景的药物研发管线临床试验,包括异基因CAR-T治疗,以及多抗原靶向疗法,如CD19/CD22 CAR-T和CD3/CD20双特异性抗体mosunetuzumab与odronextamab。文章并结合截至2022年初的最佳现有证据,总结了作者的治疗策略。
Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that has been traditionally treated with anthracycline-based chemotherapy, but approximately one-third of patients relapse after first-line therapy or have primary refractoriness. In this focused review, we discuss the 7 novel Food & Drug Administration (FDA)-approved medications for relapsed/refractory (R/R) DLBCL. We describe 5 CD19-targeted therapies, 3 of which are chimeric antigen receptor (CAR)-T cell therapies. We also highlight novel non-cell-based targeted therapies and discuss optimal sequencing considerations based on the goal of treatment, with an emphasis on CAR-T cell therapy as curative intent. We consider the limited tolerability of certain novel agents, prospects for elderly patients, and financial aspects of these approaches. We discuss advantages and limitations of these targeted therapies based on seminal clinical trials. Finally, we summarize ongoing trials involving promising agents making their way into the pharmacologic pipeline. These therapies include allogeneic CAR-T treatments and multi-antigen targeting therapies such as the CD19/CD22 CAR-T and the CD3/CD20 bispecific antibodies mosunetuzumab and odronextamab. We summarize our approach based on the best available evidence as we enter 2022.
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