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BCMA嵌合抗原受体T细胞疗法治疗后多发性骨髓瘤患者单克隆和寡克隆蛋白条带的发生率及临床意义:一项基于LEGEND-2的回顾性研究

The incidence and clinical significance of monoclonal and oligoclonal protein bands in multiple myeloma patients after BCMA-CAR-T cell therapy: A retrospective study based on LEGEND-2.

作者信息

Liu Rui, Gao Gongzhizi, Chen Hongli, Dong Ruijun, Zhang Wanggang, Zhao Wanhong, Liu Jie, Wang Jianli, Lei Bo, Wang Baiyan, Liu Jiali, Xu Xuezhu, Lin Zujie, Yang Ruoyu, Wang Yiwen, He Aili, Wang Fangxia, Bai Ju

机构信息

Department of Hematology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China.

Xi'an Key Laboratory of Hematological Diseases The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China.

出版信息

Hemasphere. 2024 Nov 19;8(11):e70054. doi: 10.1002/hem3.70054. eCollection 2024 Nov.

DOI:10.1002/hem3.70054
PMID:39564538
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11574876/
Abstract

The emergence of abnormal protein bands (APBs), also known as oligoclonal protein bands, has been documented in patients with multiple myeloma (MM) post hematopoietic stem cell transplantation. However, the incidence rate and clinical significance of APBs remain contentious. Few studies have explored the occurrence and prognostic implications of APBs in patients with MM treated with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR)-T therapy. In this retrospective study, we examined the frequency, isotypes, and duration of APBs, as well as their correlation with MM disease characteristics, treatment response, clinical outcomes, and immune signature in patients with relapsed/refractory MM who had received LCAR-B38M therapy at the Xi'an site of the phase 1 LEGEND-2 trial. Among 47 patients assessed, 23 (48.9%) developed APBs following CAR-T therapy, with IgG being the most common isotype. The median onset and duration of APBs post-CAR-T infusion were 3.6 and 5.8 months, respectively. Patients with APBs demonstrated significantly improved response to LCAR-B38M therapy, along with longer overall and progression-free survival. Furthermore, those with APBs exhibited enhanced recovery rates of immunoglobulins and higher absolute counts of white blood cells, neutrophils, and lymphocytes post-CAR-T treatment compared to those without APBs. However, no significant differences were observed between the two groups in the percentages of various T-cell subsets and natural killer cells. Overall, the presence of APBs in patients with MM following CAR-T treatment was associated with deeper remission and a more favorable prognosis, suggesting a robust humoral response and subsequent immune reconstitution.

摘要

异常蛋白条带(APBs),也称为寡克隆蛋白条带,已在造血干细胞移植后的多发性骨髓瘤(MM)患者中被记录到。然而,APBs的发生率和临床意义仍存在争议。很少有研究探讨APBs在接受B细胞成熟抗原(BCMA)特异性嵌合抗原受体(CAR)-T治疗的MM患者中的发生情况及其预后意义。在这项回顾性研究中,我们检查了复发/难治性MM患者在西安进行的1期LEGEND-2试验中接受LCAR-B38M治疗后APBs的频率、亚型、持续时间,以及它们与MM疾病特征、治疗反应、临床结局和免疫特征的相关性。在评估的47例患者中,23例(48.9%)在CAR-T治疗后出现APBs,其中IgG是最常见的亚型。CAR-T输注后APBs的中位发病时间和持续时间分别为3.6个月和5.8个月。出现APBs的患者对LCAR-B38M治疗的反应显著改善,总生存期和无进展生存期更长。此外,与未出现APBs的患者相比,出现APBs的患者在CAR-T治疗后免疫球蛋白的恢复率更高,白细胞、中性粒细胞和淋巴细胞的绝对计数更高。然而,两组在各种T细胞亚群和自然杀伤细胞的百分比方面没有观察到显著差异。总体而言,CAR-T治疗后MM患者中APBs的存在与更深的缓解和更有利的预后相关,表明存在强大的体液反应和随后的免疫重建。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/f30c3d627856/HEM3-8-e70054-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/82c845492490/HEM3-8-e70054-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/e531a4c929f0/HEM3-8-e70054-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/f30c3d627856/HEM3-8-e70054-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/82c845492490/HEM3-8-e70054-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/e531a4c929f0/HEM3-8-e70054-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09e/11574876/f30c3d627856/HEM3-8-e70054-g003.jpg

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本文引用的文献

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Early M-protein immune reconstitution after autologous haematopoietic stem cell transplantation is a good prognostic marker for patients with high-risk cytogenetic multiple myeloma.自体造血干细胞移植后早期 M 蛋白免疫重建是高危细胞遗传学多发性骨髓瘤患者的良好预后标志物。
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Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).
在中国开展的一项 1 期、单臂、开放标签、多中心研究(LEGEND-2)中,评估 LCAR-B38M 治疗复发/难治性多发性骨髓瘤的 4 年随访结果。
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International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.国际骨髓瘤工作组更新了多发性骨髓瘤的诊断标准。
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