CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:SOHO State of the Art Updates and Next Questions: Managing Relapsed Mantle Cell Lymphoma.
SOHO State of the Art Updates and Next Questions: Managing Relapsed Mantle Cell Lymphoma.
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套细胞淋巴瘤(MCL)是一种罕见的B细胞非霍奇金淋巴瘤亚型,目前疗法尚不能治愈。部分患者初始治疗后可长期缓解,但大多数患者会经历复发与缓解交替过程,并在病程中需要多线治疗。目前已有多种靶向疗法用于复发性MCL。布鲁顿酪氨酸激酶(BTK)抑制剂,包括ibrutinib、acalabrutinib和zanubrutinib,对MCL活性较强,且已获批用于复发患者。硼替佐米和来那度胺可单药或与其他药物联用。维奈克拉具有活性,可考虑用于复发性MCL,但目前尚未获监管机构批准。brexucabtagene autoleucel CAR-T 细胞疗法缓解率较高,现已获批用于复发性MCL。对于经过多线治疗后进展且身体状况良好、有积极治疗意愿的一小部分患者,异基因干细胞移植仍是一种选择,但其应用受显著毒性限制。目前复发性MCL尚无标准治疗顺序,利用疾病生物学和临床特征指导治疗决策的能力也有限。本文总结复发性MCL管理的现有证据,综述正在研究的新药及联合疗法,并介绍作者目前的治疗思路。
Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma i. e. , incurable with current therapies. While some patients experience prolonged remissions following initial therapy, most will have a relapsing-remitting course requiring several lines of treatment over the course of their disease. Several targeted therapies are now available to treat patients with relapsed MCL. The Bruton's tyrosine kinase (BTK) inhibitors, including ibrutinib, acalabrutinib, and zanubrutinib, are highly active in MCL and currently approved for treating patients with relapsed disease. Bortezomib and lenalidomide are available as monotherapy or in combination with other agents. Venetoclax is active and can be considered for use in relapsed MCL, although it is not currently approved by regulatory agencies.
Chimeric antigen receptor T-cell (CAR-T) therapy with brexucabtagene autoleucel yields high response rates and is now approved for patients with relapsed MCL. Allogeneic stem cell transplant remains an option for a small subset of medically fit and motivated patients who have progressed through multiple lines of therapy, although its use is limited by substantial toxicity.
There is currently no standard approach to sequencing therapies for patients with relapsed MCL, and the ability to utilize disease biologic and clinical characteristics to guide treatment decisions in this setting remains limited. In this review, we summarize the current evidence to guide the management of patients with relapsed MCL, review emerging agents and combination therapies that are under investigation, and outline our current treatment approach for these patients.
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