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多发性骨髓瘤患者 BCMA-CAR-T 细胞治疗后单克隆与寡克隆蛋白条带的发生率及临床意义:基于 LEGEND-2 的回顾性研究

英文原题: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.

PubMed 2024/11/19(内容时间) Hemasphere Q1 · IF 11.3(JCR 2025)

研究概要

MM 患者 CAR-T 治疗后出现 APB 与更深的缓解和更有利的预后相关,提示存在强健的体液免疫应答及随后的免疫重建。

中文摘要

多发性骨髓瘤(MM)患者造血干细胞移植后出现异常蛋白带(APB),又称寡克隆蛋白带,已有报道。然而,APB的发生率和临床意义仍存在争议。关于B细胞成熟抗原(BCMA)特异性嵌合抗原受体(CAR)T细胞治疗MM患者后APB发生及其预后意义的研究较少。在这项回顾性研究中,我们考察了西安中心参加I期LEGEND-2试验并接受LCAR-B38M治疗的复发/难治性MM患者中APB发生频率、同种型和持续时间,以及其与疾病特征、治疗应答、临床结局和免疫特征之间的关联。47例接受评估的患者中,23例(48.9%)在CAR-T治疗后出现APB,最常见同种型为IgG。CAR-T输注后APB出现时间和持续时间中位数分别为3.6个月和5.8个月。出现APB的患者对LCAR-B38M治疗应答显著改善,总生存期和无进展生存期更长。此外,与未出现APB者相比,APB患者CAR-T治疗后免疫球蛋白恢复率更高,白细胞、中性粒细胞和淋巴细胞绝对计数也更高。然而,两组在各T细胞亚群和NK细胞比例方面均无显著差异。总体而言,CAR-T治疗后MM患者出现APB与缓解更深、预后更佳相关,提示体液免疫应答强劲并随后发生免疫重建。

展开英文摘要原文

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.

论文信息

作者
Liu R、Gao G、Chen H、Dong R、Zhang W、Zhao W、Liu J、Wang J
单位
Department of Hematology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China.China
期刊
HemaSphere2024 Nov
原文标识
PubMed 39564538 · DOI 10.1002/hem3.70054