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氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描在预测嵌合抗原受体 T 细胞治疗非霍奇金淋巴瘤患者不良影响中的作用。

Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Predicting the Adverse Effects of Chimeric Antigen Receptor T Cell Therapy in Patients with Non-Hodgkin Lymphoma.

机构信息

Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

PET-CT Center, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

出版信息

Biol Blood Marrow Transplant. 2019 Jun;25(6):1092-1098. doi: 10.1016/j.bbmt.2019.02.008. Epub 2019 Feb 12.

Abstract

CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but this has not been explored in detail in any previous study. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT), are quantitative indicators of baseline tumor burden. Using FDG PET-CT, we calculated baseline and post-CAR-T cell therapy MTV and TLG in 19 patients with NHL. The median MTV was 72 cm (range, .02 to 1137.7 cm), and the median TLG was 555.9 (range, .011 to 8990.3). After a median follow-up of 5 months (range, 1 to 12 months), the best overall response rate was 79.0%. The baseline MTV and TLG did not differ significantly between patients with response and those without response (P = .62 and .95, respectively). On Cox regression analysis, baseline MTV and TLG were not significantly associated with overall survival (P = .67 and .45, respectively). Patients with mild and moderate CRS (grade 0 to 2) had significantly lower MTV and TLG than those with severe CRS (grade 3 to 4) (P = .008 for MTV comparison, P = .011 for TLG comparison). Using FDG PET-CT, we also demonstrated that CAR-T cell therapy in patients with NHL was associated with pseudoprogression and local immune activation. Our data indicate that patients with higher baseline disease burden have more severe CRS, and that CAR-T cell therapy is associated with lymphoma pseudoprogression and local immune activation.

摘要

CD19 靶向嵌合抗原受体(CAR)-T 细胞疗法在复发/难治性非霍奇金淋巴瘤(NHL)患者中显示出巨大疗效,但与严重的不良反应相关,如细胞因子释放综合征(CRS)。有人推测 NHL 基线疾病负担可能会影响临床结局和 CRS,但这在以前的任何研究中都没有得到详细探讨。氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(FDG PET-CT)测量的代谢肿瘤体积(MTV)和总病变糖酵解(TLG)是基线肿瘤负担的定量指标。我们使用 FDG PET-CT 计算了 19 例 NHL 患者的基线和 CAR-T 细胞治疗后 MTV 和 TLG。MTV 的中位数为 72cm(范围为 0.02 至 1137.7cm),TLG 的中位数为 555.9(范围为 0.011 至 8990.3)。中位随访 5 个月(范围为 1 至 12 个月)后,最佳总体缓解率为 79.0%。有缓解和无缓解的患者之间的基线 MTV 和 TLG 无显著差异(P=0.62 和 0.95)。在 Cox 回归分析中,基线 MTV 和 TLG 与总生存均无显著相关性(P=0.67 和 0.45)。轻度和中度 CRS(0 至 2 级)患者的 MTV 和 TLG 明显低于重度 CRS(3 至 4 级)患者(MTV 比较的 P=0.008,TLG 比较的 P=0.011)。我们还通过 FDG PET-CT 证明,NHL 患者的 CAR-T 细胞治疗与假性进展和局部免疫激活相关。我们的数据表明,基线疾病负担较高的患者 CRS 更严重,CAR-T 细胞治疗与淋巴瘤假性进展和局部免疫激活相关。

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