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糖皮质激素对接受 CAR-T 治疗的复发/难治性多发性骨髓瘤患者短期与长期结局的影响

英文原题:Impact of glucocorticoids on short-term and long-term outcomes in patients with relapsed/refractory multiple myeloma treated with CAR-T therapy.

查看英文原题

Impact of glucocorticoids on short-term and long-term outcomes in patients with relapsed/refractory multiple myeloma treated with CAR-T therapy.

PubMed 2022/08/23(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

在本研究中,GCs 的给药、剂量、时机和持续时间不影响 CAR-T 细胞在 RRMM 中的临床疗效。

研究思路结论见上方概要

糖皮质激素(GCs)常用于治疗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)。GCs对复发/难治性多发性骨髓瘤(RRMM)CAR-T 细胞治疗疗效的影响尚未完全明确。我们评估了GCs对接受CAR-T 细胞治疗的RRMM患者临床结局的影响。

本研究纳入2017年6月至2020年12月在本中心接受CAR-T 细胞治疗的RRMM患者。患者被分为使用GC组(GC组)和未使用GC组(NGC组)。CRS或ICANS根据美国移植与细胞治疗学会共识分级系统进行分级。疗效状态根据IMWG统一疗效标准进行评估。计算缓解持续时间(DOR)、无进展生存期(PFS)和总生存期(OS)。

本研究共纳入71例患者。在NGC组(40例患者)中,34例(85%)对CAR-T 细胞治疗有反应,包括16例(40%)严格完全缓解(sCR)、7例(17.5%)完全缓解(CR)、5例(12.5%)非常好的部分缓解(VGPR)和6例(15%)部分缓解(PR)。NGC组的总体缓解率(ORR)和完全缓解率(CRR)分别为85%和57.5%。在GC组(31例患者)中,29例(93.5%)有反应,包括11例(35.5%)sCR、9例(29%)CR、2例(6.4%)VGPR和7例(22.6%)PR。两组之间的ORR和CRR差异无统计学意义。GC的剂量、持续时间和使用时机不影响ORR和CRR。在中位随访28.2个月时,GC组的中位PFS为20.4个月(95% CI,7.9至32.9),中位OS为36.6个月(95% CI,25.9至47.2)。NGC组的中位PFS和OS分别为13.7个月(95% CI,8.8至18.6)和27.5个月(95% CI,14.1至41.0)。GC组与NGC组之间的PFS或OS均无显著差异。GC组和NGC组中达到CR或更好缓解的患者的中位DOR差异无统计学意义(p = 0.17)。较早、延长使用和高剂量GC与PFS或OS的任何影响均无关。此外,GC对CAR-T 细胞增殖没有影响。

展开英文摘要原文

Glucocorticoids (GCs) are often used to treat cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The effects of GCs on the efficacy of CAR-T cell treatment in relapsed/refractory multiple myeloma (RRMM) have not been fully established. We evaluated the impact of GCs on clinical outcomes of RRMM patients treated with CAR-T cells.

This study involved RRMM patients treated with CAR-T cells at our center between June 2017 and December 2020. Patients were stratified into GC-used group (GC-group) and non-GC-used group (NGC-group). CRS or ICANS was graded on the basis of the American Society of Transplantation and Cellular Therapy consensus grading system. Response status was evaluated by the IMWG Uniform Response Criteria. The duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were calculated. RESULT: A total of 71 patients were included in this study. In the NGC group (40 patients), 34 (85%) had responses to CAR-T cell therapy, including 16 (40%) stringent complete response (sCR), seven (17.5%) complete response (CR), five (12.5%) very good partial response (VGPR), and six (15%) partial response (PR). The overall response rate (ORR) and complete response rate (CRR) in the NGC group were 85% and 57.5%. In the GC group (31 patients), 29 (93.5%) had responses, including 11 (35.5%) sCR, nine (29%) CR, two (6.4%) VGPR, and seven (22.6%) PR. Differences in ORR and CRR between the two groups were insignificant. The dose, duration, and timing of GCs did not affect ORR and CRR. At a median follow-up of 28.2 months, the median PFS was 20.4 months (95% CI, 7.9 to 32.9) while the median OS was 36.6 months (95% CI, 25.9 to 47.2) for the GC group. The median PFS and OS for the NGC group were 13.7 months (95% CI, 8.8 to 18.6) and 27.5 months (95% CI, 14.1 to 41.0). There were no significant differences in either PFS or OS between the GC group and the NGC group. Differences in median DOR for the patients with CR or better in the GC group and NGC group were not significant ( p = 0.17). Earlier, prolonged use and high dose of GCs were not associated with any effects on either PFS or OS. Additionally, GCs had no effects on CAR-T cell proliferation.

Administration of GCs, dose, timing, and duration does not influence the clinical efficacy of CAR-T cells in RRMM in this study.

论文信息

作者
Wang X、Qi Y、Li H、Liu F、Cao J、Chen W、Wang Y、Qi K
单位
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.China
期刊
Frontiers in immunology2022
原文标识
PubMed 36081517 · DOI 10.3389/fimmu.2022.943004