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:Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival.
Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival.
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治疗前营养不良和恶病质与 CAR-T 患者不良结局显著相关,其中 mGPS 恶病质状态与较差的总生存期独立相关。在这一新领域开展进一步研究至关重要,以确认营养问题的程度和影响,协助实施营养学路径,并确定可能改善结局的干预措施。
嵌合抗原受体(CAR)T细胞疗法已成为难治性或复发性B细胞恶性肿瘤患者的一种革命性治疗方法。然而,相当比例的患者会出现不良结局,包括严重的炎症性毒性和复发。恶病质和营养不良是许多癌症患者已知的继发综合征,归因于活动性恶性肿瘤、全身性炎症和累积治疗负担的影响;然而,仍需进一步研究以准确描述CAR-T 细胞患者的这些问题。本服务评估的目的是探讨CAR-T 细胞疗法患者营养状况(营养不良和恶病质)的变化及其对患者结局(包括生存)的潜在影响。此外,我们描述了在伦敦一家三级转诊中心该特定患者群体中饮食资源的利用情况。
纳入2019年4月1日至2021年9月21日期间在伦敦大学学院医院接受已获批CD19靶向CAR-T 细胞治疗的成人血液病患者。数据从治疗知情同意时开始收集,贯穿整个住院期至出院日:体重(BW)、C反应蛋白、白蛋白、乳酸脱氢酶、营养风险筛查评分(医院特定)及营养师干预。同时记录临床结局,如12个月全因死亡率、重症监护病房(ICU)入住、高级别毒性反应和住院时间(LoS)。恶病质和营养不良分别采用改良格拉斯哥预后评分(mGPS)和全球营养不良领导倡议(GLIM)共识进行定义。
纳入114例B细胞非霍奇金淋巴瘤(n = 109)和B细胞急性淋巴细胞白血病(n = 5)患者(55.6 15.1岁;57%为男性),接受axicabtagene ciloleucel(n = 89)和tisagenlecleucel(n = 25)治疗。治疗的中位LoS为34(27-38)天。治疗前,31.5%的患者出现营养不良,43.6%的患者被识别为前恶病质/难治性恶病质(mGPS)。治疗前营养状态的改变与输注后患者不良结局显著相关;mGPS与较差的总生存期独立相关(HR = 3.158,CI = 1.36-7.323,p = 0.007),营养不良和mGPS与LoS延长(p = 0.037)、脓毒症(p = 0.022)和ICU入住(p = 0.039)相关。住院期间,患者出现显著的BW下降(-5.6%(-8.8至-2.4);p=<0.001),68.4%出现营养不良。住院期间营养不良筛查识别出57%的患者存在风险,66.6%的患者被转诊至营养科;然而,治疗前缺乏营养不良筛查和营养科转诊。
Adult haematology patients receiving licensed CD19-targeting CAR T-cell therapy at University College London Hospital between 01/04/19 and 01/09/21 were included. Data were collected from the time of treatment consent, and throughout admission to day of discharge: body weight (BW), C-reactive protein, albumin, lactate dehydrogenase, nutrition-risk screening scores (hospital-specific) and dietetic input. Clinical outcomes such as 12-month all-cause mortality, intensive care unit (ICU) admission, high-grade toxicities, and length of hospital stay (LoS) were also recorded. Cachexia and malnutrition were defined using the modified Glasgow Prognostic Score (mGPS) and Global Leadership Initiative on Malnutrition (GLIM) consensus, respectively.
114 patients (55.6 15.1 years; 57% males) with B-cell non-Hodgkin's lymphoma (n = 109) and B-cell acute lymphoblastic leukaemia (n = 5), receiving axicabtagene ciloleucel (n = 89) and tisagenlecleucel (n = 25) were included. Median LoS for treatment was 34 (27-38) days. Prior to treatment, 31.5% of patients developed malnutrition, with pre-cachexia/refractory cachexia (mGPS) identified in 43.6% of patients. This altered nutritional status pre-treatment was significantly associated with adverse patient outcomes post-infusion; mGPS was independently associated with inferior overall survival (HR = 3.158, CI = 1.36-7.323, p = 0.007), with malnutrition and mGPS associated with increased LoS (p = 0.037), sepsis (p = 0.022) and ICU admission (p = 0.039). During admission, patients experienced significant BW loss (-5.6% (-8.8 to -2.4); p=<0.001), with 68.4% developing malnutrition. Malnutrition screening during admission identified 57% patients at-risk, with 66.6% of patients referred to dietetics; however, there was a lack of malnutrition screening and dietetic referrals prior to treatment.
Pre-treatment malnutrition and cachexia was significantly associated with adverse CAR T patient outcomes, including mGPS cachexia status independently associated with inferior overall survival. Further research in this novel space is essential to confirm the extent and impact of nutritional issues, to assist with implementing dietetic pathways, and to identify potential interventions with a view to optimising outcomes.
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