CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prospective Assessment of Quality of Life and Patient-Reported Toxicities Over the First Year After Chimeric Antigen Receptor T-Cell Therapy.
Prospective Assessment of Quality of Life and Patient-Reported Toxicities Over the First Year After Chimeric Antigen Receptor T-Cell Therapy.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
嵌合抗原受体(CAR)T细胞疗法已改变复发/难治性大B细胞淋巴瘤(LBCL)患者的生存结局,但它与多种副作用相关。本研究考察了治疗后第一年内患者报告的生活质量(QoL)和毒性变化,以及QoL较差和毒性的危险因素。LBCL患者在输注前以及输注后90、180和360天完成了评估QoL和毒性严重程度的问卷。混合模型用于考察QoL和毒性随时间的变化,以及QoL和毒性变化的临床调节因素。患者报告在治疗后一年内身体功能和疲劳有所改善(P值<.01),但疼痛、焦虑或抑郁随时间没有变化。第90天有活动性疾病的患者在所有输注后时间点报告了更多的身体功能障碍(Ps .01),与治疗有应答的患者相比。
同样,第90天有活动性疾病的患者报告抑郁随时间恶化,以至于在第360天,有活动性疾病患者的抑郁症状比无活动性疾病患者更差(P = .02)。接受过4线及以上既往治疗的患者报告疼痛和焦虑随时间恶化,以至于在第360天,既往接受过4线或更多线治疗的患者疼痛和焦虑均显著差于接受较少线治疗的患者(Ps .01)。关于毒性,患者报告总体毒性负担至第180天下降,随后在第360天恶化(P = .02)。大多数患者在每个时间点报告至少一或两种2级毒性。患者在接受CAR-T 细胞治疗后,生活质量保持不变或有所改善,但活动性疾病和既往治疗线数较多与随时间推移更差的生活质量结局相关。毒性严重程度在治疗后前6个月内也有所改善,但此后恶化,尤其是在治疗后仍有活动性疾病的患者中。
Chimeric antigen receptor (CAR) T-cell therapy has transformed survival outcomes in patients with relapsed and refractory large B-cell lymphoma (LBCL), but it is associated with a variety of side effects.
This study examined changes in patient-reported quality of life (QoL) and toxicities, as well as risk factors for worse QoL and toxicities, in the first year after treatment. Patients with LBCL completed questionnaires assessing QoL and toxicity severity before infusion, and 90, 180, and 360 days after infusion. Mixed models were used to examine changes in QoL and toxicities over time, and clinical moderators of change in QoL and toxicities. Patients reported improvements in physical functioning and fatigue in the year after treatment (P values <. 01), but there were no changes in pain, anxiety, or depression over time. Patients with active disease at day 90 reported more physical dysfunction at all postinfusion timepoints (Ps . 01) compared to patients who responded to treatment. Similarly, patients with active disease at day 90 reported worsening depression over time, such that at day 360, depressive symptoms were worse for patients with active disease than patients without active disease (P = .
02). Patients treated with 4+ lines of prior therapy reported worsening pain and anxiety over time, such that at day 360, both pain and anxiety were significantly worse for patients previously treated with 4 of more lines of therapy than patients treated with fewer lines of therapy (Ps . 01). Regarding toxicities, patients reported decreasing overall toxicity burden up to day 180, with subsequent worsening at day 360 (P = . 02).
Most patients reported at least one or two grade 2 toxicities at each timepoint. Patients demonstrated unchanging or improved QoL after treatment with CAR T-cell therapy, but active disease and greater prior lines of therapy were associated with worse QoL outcomes over time. Toxicity severity also improved during the first 6 months post-treatment, but worsened thereafter, particularly among patients with active disease after treatment.
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