Valtis Yannis K, Devlin Sean, Shouval Roni, Rejeski Kai, Corona Magdalena, Luna De Abia Alejandro, Rivas-Delgado Alfredo, Luttwak Efrat, Cassanello Giulio, Landego Ivan, Schöder Heiko, Bedmutha Akshay, Boardman Alexander, Shah Gunjan L, Scordo Michael, Perales Miguel-Angel, Salles Gilles, Palomba M Lia, Shah Urvi A, Park Jae H
Cell Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood Adv. 2025 Jan 14;9(1):151-161. doi: 10.1182/bloodadvances.2024014555.
Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of lymphoma, yet many patients relapse. Several prognostic markers have been associated with CAR T-cell outcomes, such as tumor burden, response to bridging chemotherapy, and laboratory parameters at the time of lymphodepletion or infusion. The effect of cancer cachexia and weight loss before CAR T cells on toxicity and outcomes is not well understood. Here, we present a retrospective single-institution cohort study of 259 patients with lymphoma treated with CAR T cells between 2017 and 2023. We observed that patients with >5% decrease in their body mass index in the 3 months preceding CAR T-cell treatment (weight loss group; all meeting one of the commonly accepted definitions of cancer cachexia) had higher disease burden and inflammatory parameters (C-reactive protein, ferritin, interleukin-6, and tumor necrosis factor α) at the time of lymphodepletion and CAR T-cell infusion. Patients with weight loss experienced higher rates of grade 3+ neurotoxicity and early hematotoxicity, but those effects were not seen upon multivariable adjustment. However, in both univariate and multivariable analysis, patients with weight loss had worse response rates, overall survival, and event-free survival, indicating that weight loss is an independent poor prognostic factor. Our data suggest that weight loss in the 3 months preceding CAR T-cell therapy represents a worrisome "alarm signal" and a potentially modifiable factor, alongside tumor burden and inflammation, and warrants further investigation in patients treated with CAR T-cell therapy.
嵌合抗原受体（CAR）T细胞疗法已经改变了淋巴瘤的治疗方式，但仍有许多患者复发。一些预后标志物与CAR T细胞治疗的结果相关，如肿瘤负荷、对桥接化疗的反应以及淋巴细胞清除或输注时的实验室参数。CAR T细胞治疗前癌症恶病质和体重减轻对毒性和治疗结果的影响尚不清楚。在此，我们进行了一项回顾性单中心队列研究，纳入了2017年至2023年间接受CAR T细胞治疗的259例淋巴瘤患者。我们观察到，在CAR T细胞治疗前3个月体重指数下降>5%的患者（体重减轻组；均符合癌症恶病质的常用定义之一）在淋巴细胞清除和CAR T细胞输注时疾病负担和炎症参数（C反应蛋白、铁蛋白、白细胞介素-6和肿瘤坏死因子α）更高。体重减轻的患者3级及以上神经毒性和早期血液毒性发生率更高，但多变量调整后未观察到这些影响。然而，在单变量和多变量分析中，体重减轻的患者缓解率、总生存期和无事件生存期均较差，表明体重减轻是一个独立的不良预后因素。我们的数据表明，CAR T细胞治疗前3个月的体重减轻是一个令人担忧的“警示信号”，是一个潜在的可改变因素，与肿瘤负荷和炎症一起，值得在接受CAR T细胞治疗的患者中进一步研究。
