决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Patient-reported outcomes after idecabtagene vicleucel vs. ciltacabtagene autoleucel CAR-T for multiple myeloma.
在 99 例参与者中,ide-cel 受者(n = 49)年龄大于 cilta-cel 受者(n = 50)(中位 73 vs.
这是首项评估接受标准治疗CAR-T 细胞疗法的复发/难治性多发性骨髓瘤(RRMM)患者报告结局(PRO)变化轨迹,并比较 idecabtagene vicleucel(ide-cel)与 ciltacabtagene autoleucel(cilta-cel)两组轨迹的研究。参与者在入组/基线(淋巴细胞清除前)、输注日(D0)及 D7、D14、D21、D30、D60 和 D90 完成健康相关生活质量(HRQOL)和症状问卷。采用分段增长曲线模型评估 D7 前后 PRO 变化。在 99 名参与者中,ide-cel 组(n=49)年龄大于 cilta-cel 组(n=50)(中位年龄 73 对 64 岁,p<0.001)。多项 PRO 在 D7 前恶化、D7 后改善,包括总体 HRQOL、身体健康、功能健康、疲劳、身体功能和社会功能(p 值均 <0.05)。另有多项 PRO 在 D7 前稳定、D7 后改善,包括焦虑、睡眠障碍、疼痛干扰和疼痛强度(p 值均 <0.05)。两组在 D7 前的社会健康轨迹(p=0.01)和 D7 后的认知功能轨迹(p=0.001)存在差异。接受标准治疗 CAR-T 的 RRMM 患者,无论 CAR-T 类型,其 PRO 轨迹总体相似;多数 PRO 在治疗前期先恶化或保持稳定,治疗后则显著改善。未来研究应进一步考察治疗组间社会健康和认知功能的潜在差异,以及治疗后 D90 以后的 PRO 轨迹。
This was the first study to assess patient-reported outcome (PRO) trajectories among patients with relapsed/refractory multiple myeloma (RRMM) receiving standard of care chimeric antigen receptor T-cell therapy (CAR-T) and to compare PRO trajectories by treatment group, idecabtagene vicleucel (ide-cel) vs. ciltacabtagene autoleucel (cilta-cel). Participants completed health-related quality of life (HRQOL) and symptom surveys at enrollment/baseline (pre-lymphodepletion), infusion day(D)0, D7, D14, D21, D30, D60, and D90. Piecewise growth curve models assessed PRO trajectories pre-D7 and post-D7. Among 99 participants, ide-cel recipients (n = 49) were older than cilta-cel recipients (n = 50) (median 73 vs. 64 years, p < 0.001). Many PROs worsened pre-D7 and improved post-D7, including overall HRQOL, physical well-being, functional well-being, fatigue, physical function, and social function (p-values < 0.05). Several PROs were stable pre-D7 and improved post-D7, including anxiety, sleep disturbance, pain interference, and pain intensity (p-values < 0.05). There were differences between groups in the trajectories of social well-being pre-D7 (p = 0.01) and cognitive function post-D7 (p = 0.001). Patients with RRMM receiving standard of care CAR-T had similar PRO trajectories regardless of CAR-T type, with most PROs initially worsening or stable before significantly improving post-treatment. Future studies should investigate potential differences by treatment for social well-being and cognitive function as well as PRO trajectories beyond D90 post-treatment.
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