Inflammatory signatures for quick diagnosis of life-threatening infection during the CAR T-cell therapy
Posted on 2019-10-23 - 08:28
Abstract Background Chimeric antigen receptor-modified (CAR) T-cell immunotherapy is a novel promising therapy for treatment of B-cell malignancy. Cytokine release syndrome (CRS) and infection are the most common adverse events during CAR T-cell therapy. Similar clinical presentation of concurrent CRS and infection makes it difficult to differentially diagnose and timely treat the condition. Methods We analyzed the features of infection events during the first 30 days after CAR T-cell infusion (CTI) in 109 patients from three clinical trials (ChiCTR-OPN-16008526, ChiCTR-OPC-16009113, ChiCTR-OPN-16009847). Based on the dynamic changes of interleukin (IL)-6 and ferritin, we proposed the “double peaks of IL-6” pattern as a feature of life-threatening infection during the first 30 days after CTI. Meanwhile, we screened candidate biomarkers from 70-biomarker panel to establish a prediction model for life-threatening infection. Results In this study, 19 patients (17.4%) experienced a total of 19 infection events during the first 30 days after CAR T-cell infusion. Eleven patients (10.1%) had grade 4–5 infection, which were all bacterial infection and predominantly sepsis (N = 9). “Double peaks of IL-6” appeared in 9 out of 11 patients with life-threatening infection. The prediction model of three-cytokines (IL-8, IL-1β and interferon-γ) could predict life-threatening infection with high sensitivity (training: 100.0%; validation: 100.0%) and specificity (training: 97.6%; validation: 82.8%). On base of the aforementioned methods, we proposed a workflow for quick identification of life-threatening infection during CAR T-cell therapy. Conclusions In this study, we worked out two diagnostic methods for life-threatening infection during CAR T-cell therapy by analyzing inflammatory signatures, which contributed to reducing risks of infection-induced death.
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Luo, Hui; Wang, Na; Huang, Liang; Zhou, Xiaoxi; Jin, Jin; Li, Chunrei; et al. (2019). Inflammatory signatures for quick diagnosis of life-threatening infection during the CAR T-cell therapy. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4708952.v1
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AUTHORS (19)
HL
Hui Luo
NW
Na Wang
LH
Liang Huang
XZ
Xiaoxi Zhou
JJ
Jin Jin
CL
Chunrei Li
DW
Di Wang
BX
Bin Xu
JX
Jinhuan Xu
LJ
Lijun Jiang
JW
Jue Wang
YC
Yang Cao
YX
Yi Xiao
QZ
Qian Zhang
XM
Xia Mao
SL
Songya Liu
LC
Liting Chen
MX
Min Xiao
JZ
Jianfeng Zhou