目的: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革命性治疗方法。然而,相当比例的患者经历负面结果,包括严重的炎症毒性和复发。恶病质和营养不良是许多癌症患者已知的继发性综合征,归因于活动性恶性肿瘤的影响,全身性炎症,和累积治疗负担;然而,需要进一步的研究来准确描述CART细胞患者的这些问题。这项服务评估的目的是探索CART细胞治疗患者的营养状况(营养不良和恶病质)的变化以及对患者预后(包括生存)的潜在影响。此外,我们描述了伦敦三级转诊中心这一特定患者人群的饮食资源利用情况.
方法:包括19年04月01日至21年09月01日在伦敦大学学院医院接受CD19靶向CART细胞治疗的成人血液病患者。数据收集自同意治疗的时间,以及整个入院至出院日: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)和饮食输入。临床结果,如12个月全因死亡率,重症监护病房(ICU)入院,高级毒性,并记录住院时间(LoS)。使用改良的格拉斯哥预后评分(mGPS)和全球营养不良领导力倡议(GLIM)共识来定义恶病质和营养不良。分别。
结果:114例(55.6±15.1岁;57%为男性)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),包括接受axicabtageneciloleucel(n=89)和tisagenlecleucel(n=25)。治疗的LoS中位数为34(27-38)天。治疗前,31.5%的患者出现营养不良,在43.6%的患者中发现恶病质/难治性恶病质(mGPS)。治疗前营养状况的改变与输注后患者的不良结局显着相关;mGPS与较差的总生存率独立相关(HR=3.158,CI=1.36-7.323,p=0.007)。营养不良和mGPS与LoS增加相关(p=0.037),脓毒症(p=0.022)和ICU入院(p=0.039)。入院期间,患者经历了显着的BW损失(-5.6%(-8.8至-2.4);p=<0.001),68.4%的人营养不良。入院期间的营养不良筛查确定了57%的风险患者,66.6%的患者提到营养学;然而,治疗前缺乏营养不良筛查和饮食转诊.
结论:治疗前营养不良和恶病质与CAR-T患者不良预后显著相关,包括mGPS恶病质状态与整体生存率低独立相关。在这个新颖的空间中进行进一步的研究对于确认营养问题的程度和影响至关重要。协助实施饮食途径,并确定潜在的干预措施,以期优化结果。
OBJECTIVE: Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies. However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse. Cachexia and malnutrition are known secondary syndromes in many cancer patients, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterise these issues in CAR T-cell patients. The aims of this service evaluation were to explore the changes in nutritional status (malnutrition and cachexia) in CAR T-cell therapy patients and the potential impact on patient outcomes including survival. Additionally, we describe the utilisation of dietetic resources in this specific patient population in a London tertiary referral centre.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.