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脂质体长春新碱作为复发难治性弥漫性大B细胞淋巴瘤CAR-T治疗前的桥接治疗?

Liposomal Vincristine as a Bridge Therapy Prior to CAR-T Therapy in Relapsed and Refractory Diffuse Large B-Cell Lymphoma?

作者信息

Chadha Juskaran, Hussein Shafinaz, Zhan Yougen, Shulman Jonah, Brody Joshua, Ratner Lynn, Steinberg Amir

机构信息

Department of Hematology & Medical Oncology, Lenox Hill Hospital Northwell Health, New York, NY, USA.

Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.

出版信息

Int J Hematol Oncol Stem Cell Res. 2019 Apr 1;13(2):102-107.

Abstract

We report a case of a 76-year-old male with a history of relapsed and refractory diffuse large B-cell lymphoma (DLBCL).Our patient was initially treated with front line chemotherapy along with central nervous system (CNS) prophylaxis with complete response. He subsequently relapsed, was sensitive to second-line chemotherapy, and underwent autologous stem cell transplantation achieving a complete remission. Only a few months after transplant, the patient suffered his second relapse and was deemed a candidate for Chimeric Antigen Receptor T-Cell Therapy (CAR-T). Given his aggressive disease, combined with the time needed to generate CAR-T cells, a multidisciplinary team recommended to treat our patient with liposomal vincristine in combination with rituximab as a bridge therapy. Durable responses have been seen using liposomal vincristine based on results from a recent phase II trial in heavily pretreated patients with DLBCL. This therapy was effective in stabilizing and reducing active disease in our patient. This case looks to illustrate the use of liposomal vincristine in combination with immunotherapy in a novel setting bridging highly selected patients with active and refractory lymphoma prior to CAR-T. Moreover, we expanded an additional therapeutic point, highlighting the importance of optimal disease control prior to CAR-T cell harvesting, as recent literature has shown that residual malignant cells in the pheresis product may be inadvertently be transfected with the CAR gene, resulting in resistance and further relapse.

摘要

我们报告了一例76岁男性复发性难治性弥漫性大B细胞淋巴瘤(DLBCL)患者。我们的患者最初接受一线化疗并进行中枢神经系统(CNS)预防,获得完全缓解。随后他复发,对二线化疗敏感,并接受自体干细胞移植,实现完全缓解。移植仅几个月后,患者再次复发,被认为是嵌合抗原受体T细胞疗法(CAR-T)的候选者。鉴于其侵袭性疾病,结合生成CAR-T细胞所需的时间,一个多学科团队建议用脂质体长春新碱联合利妥昔单抗治疗我们的患者作为桥接疗法。根据最近一项针对重度预处理的DLBCL患者的II期试验结果,使用脂质体长春新碱已观察到持久反应。这种疗法有效地稳定并减少了我们患者的活动性疾病。该病例旨在说明脂质体长春新碱与免疫疗法联合在一种新环境中的应用,即在CAR-T之前为高度选择的活动性和难治性淋巴瘤患者提供桥接治疗。此外,我们扩展了另一个治疗要点,强调在采集CAR-T细胞之前实现最佳疾病控制的重要性,因为最近的文献表明,单采产品中的残留恶性细胞可能会无意中被CAR基因转染,导致耐药和进一步复发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5faa/6660481/5dd5235e988b/IJHOSCR-13-102-g001.jpg

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