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嵌合抗原受体 T 细胞疗法在不适合自体移植的大 B 细胞淋巴瘤患者中的应用。

CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

机构信息

Department of Haematology, King's College Hospital, London, UK.

Cancer Research UK & UCL Cancer Trials Centre, UCL Cancer Institute, University College London, London, UK.

出版信息

Br J Haematol. 2023 Jul;202(1):65-73. doi: 10.1111/bjh.18810. Epub 2023 Apr 20.


DOI:10.1111/bjh.18810
PMID:37082780
Abstract

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.

摘要

患有合并症和/或高龄的大 B 细胞淋巴瘤 (LBCL) 患者越来越多地被考虑接受 CD19 CAR T 治疗,但在身体状况较差的患者人群中,CAR T 治疗的临床获益数据仍然有限。我们分析了英国国家 CAR T 临床小组批准接受 axicabtagene ciloleucel(axi-cel)或 tisagenlecleucel(tisa-cel)治疗的连续患者的结果,根据其自体干细胞移植 (ASCT) 的适宜性进行分层。在批准的 404 名患者中,81 名(20%)被认为不适合进行 ASCT。与 ASCT 适宜患者相比,不适合进行 ASCT 的患者更有可能接受 tisa-cel 治疗(52%比 48%),而 ASCT 适宜患者则为 20%比 80%;p<0.0001。从批准到输注的脱落率在 ASCT 不适合组中明显更高(34.6%比 23.5%;p=0.042)。在输注患者中,两组的缓解率、无进展生存期和总生存期相似。ASCT 不适合的患者中,CAR T 的耐受性良好,≥3 级细胞因子释放综合征和神经毒性的发生率分别为 2%和 11%。这项多中心真实世界队列研究的结果表明,在仔细选择的老年患者和不适合移植的合并症患者中,可以安全地给予 CD19 CAR T。

相似文献

[1]
CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Br J Haematol. 2023-7

[2]
Real-World Outcomes with Chimeric Antigen Receptor T Cell Therapies in Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.

Transplant Cell Ther. 2024-1

[3]
Cost-Effectiveness of Chimeric Antigen Receptor T Cell Therapy in Patients with Relapsed or Refractory Large B Cell Lymphoma: No Impact of Site of Care.

Adv Ther. 2022-8

[4]
A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience.

Br J Haematol. 2022-8

[5]
A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma.

Nat Med. 2022-10

[6]
Axicabtagene Ciloleucel versus Tisagenlecleucel for Relapsed or Refractory Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.

Transplant Cell Ther. 2024-6

[7]
Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.

Haematologica. 2023-1-1

[8]
Single center, real-world retrospective study of CAR-T cell therapy for relapsed/refractory large B-cell lymphoma beyond second line: five-year results at the University Hospitals Leuven.

Acta Clin Belg. 2024-8

[9]
Patterns of Use, Outcomes, and Resource Utilization among Recipients of Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B Cell Lymphomas.

Transplant Cell Ther. 2022-10

[10]
Outcomes of CD19-Directed Chimeric Antigen Receptor T Cell Therapy for Transformed Nonfollicular Lymphoma.

Transplant Cell Ther. 2023-6

引用本文的文献

[1]
Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.

J Hematol Oncol. 2024-8-6

[2]
Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis.

Hemasphere. 2024-6-13

[3]
Axicabtagene Ciloleucel versus Tisagenlecleucel for Relapsed or Refractory Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.

Transplant Cell Ther. 2024-6

[4]
Targeted Treatment of Adults with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Tafasitamab in Context.

Onco Targets Ther. 2023-7-20

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