Inflammatory signatures for quick diagnosis of life-threatening infection during the CAR T-cell therapy.

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.

• Authors: Hui Luo, Na Wang, Liang Huang, Xiaoxi Zhou, Jin Jin, Chunrei Li, Di Wang, Bin Xu, Jinhuan Xu, Lijun Jiang, Jue Wang, Yang Cao, Yi Xiao, Qian Zhang, Xia Mao, Songya Liu, Liting Chen, Min Xiao, Jianfeng Zhou
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 7 Issue 1 Pg. 271 (10 22 2019) ISSN: 2051-1426 [Electronic] England
• PMID: 31640816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Inflammation Mediators

Topics

• Adolescent
• Adult
• Aged
• Algorithms
• Biomarkers
• Cytokines (blood)
• Early Diagnosis
• Female
• Humans
• Immunotherapy, Adoptive (adverse effects, methods)
• Infections (blood, diagnosis, etiology)
• Inflammation Mediators (blood)
• Male
• Middle Aged
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (complications, immunology, therapy)
• Prognosis
• Severity of Illness Index
• Young Adult