CAR - T细胞治疗高危复发/难治性DLBCL的现实预后优化:回顾和案例分析

IF 3.2 Q2 ONCOLOGY
Gloria Iacoboni, María Pérez Raya
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引用次数: 0

摘要

嵌合抗原受体(CAR)T细胞疗法能有效治疗弥漫性大B细胞淋巴瘤(DLBCL)患者,甚至是那些高级别疾病患者。然而,它也有其独特的安全性,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),要想获得最大疗效,必须对这些事件进行强有力的管理。本视频直播旨在概述一位接受CAR T细胞疗法治疗复发/难治性(r/r)DLBCL患者的管理情况。2005年1月,患者被诊断为非典型慢性淋巴细胞白血病(CLL),并接受了两个周期的氟达拉滨和环磷酰胺治疗,后因皮肤毒性而停药。2007年,患者病情进展,接受了阿来珠单抗治疗。2018 年 1 月,患者被确诊为 DLBCL(非皮质中心、IV-A 期、骨髓浸润);与之前的 CLL 进行的克隆分析结果为阴性。2018年3月,患者接受了利妥昔单抗-环磷酰胺-多柔比星-长春新碱-强的松龙(R-CHOP)一线治疗,共6个周期。此时,正电子发射断层扫描(PET)显示病情完全缓解。不幸的是,2018 年 12 月,他们的病情复发,于是开始接受利妥昔单抗、依托泊苷、阿糖胞苷、顺铂和泼尼松(R-ESHAP)的二线治疗。在2019年2月接受第二个周期的R-ESHAP治疗后,患者病情进展,三线治疗采用利妥昔单抗+伊夫法胺、吉西他滨、长春瑞滨和泼尼松(R-IGEV),共四个周期。2019年5月,患者接受了最后一个周期的R-IGEV治疗,但病情有所进展。2019 年 7 月,患者接受了 tisagenlecleucel 输注。作者描述了 CAR T 细胞疗法的有效性以及如何处理所遇到的不良事件(AEs),包括 CRS 和 ICANS。tisagenlecleucel治疗DLBCL的真实世界证据研究结果与关键临床试验中观察到的结果相似。总之,CAR T细胞疗法对高风险r/r DLBCL患者是有效的,并能获得持久的反应。然而,长期随访是警惕晚期AEs和潜在淋巴瘤复发的关键。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) DLBCL with CAR T Cell Therapy: A Vodcast and Case Example.

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.

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来源期刊
CiteScore
3.40
自引率
0.00%
发文量
31
审稿时长
6 weeks
期刊介绍: Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of clinical therapies. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital features and plain language summaries Oncology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case by case basis and should be sent to the journal editor. Copyright Oncology and Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0 Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of £3650/€4500/$5100. The journal will consider fee discounts for developing countries and this is decided on a case by case basis. Open Access All articles published by Oncology and Therapy are published open access Contact For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.
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