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1440 Clinical Characterization and Risk Factors Associated with Cytokine Release Syndrome Induced By COVID-19 and Chimeric Antigen Receptor T-Cell Therapy

Program: Oral and Poster Abstracts
Session: 704. Immunotherapies: Poster I
Hematology Disease Topics & Pathways:
CRS, Coronaviruses, SARS-CoV-2/COVID-19, Adverse Events
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Ruimin Hong1*, Houli Zhao, MD2*, Yiyun Wang3*, Yu Chen4*, Hongliu Cai5*, Yongxian Hu, MD3*, Guoqing Wei, MD2* and He Huang, MD, PhD2,3,6,7,8,9

1Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
2Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
3Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
4Department of Clinical Laboratory, Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, Zhejiang, China
5Department of Surgical Intensive Care Unit (SICU), Department of Surgical Intensive Care Unit (SICU), The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China., Zhejiang, China
6the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
7Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China
8Institute of Hematology, Zhejiang University, Hangzhou, China
9Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

Background: An excessive immune response during coronavirus disease (COVID-19) can induce cytokine release syndrome (CRS), which is associated with life-threatening complications and disease progression.

Methods: This study was aimed to investigate the differences and similarities between CRS induced by COVID-19 and CAR-T therapy, then provide valuable experiences for early identification and controlling CRS progression in COVID-19. We retrospectively evaluated the clinical characteristics of severe CRS (sCRS, grade 3–4) induced by COVID-19 (40 patients) or chimeric antigen receptor T-cell (CAR-T) therapy as a comparator (41 patients).

Results: Grade 4 CRS was significantly more common in the COVID-19 group (15/40 [35.7%] vs. 5/41 [12.2%], P=0.008). CAR-T group had more more dramatic increase in cytokine than COVID-19 group (Figure1), including IL-2 (7.3pg/mL [IQR: 2.0–12.7] vs.1.7 [0.7–2.7], P<0.001), IL-6 (7120.6 pg/mL [1066.8–15 136.4] vs. 110.3 [41.7–728.1], P<0.001), IL-10 ( 174.5pg/mL [61.7, 434.6] vs. 10.1 [6.3–20.6], P<0.001) and IFN-γ (1308.5pg/mL [296.6, 3108.2] vs .35.0 [16.9–60.8], P<0.001). Interestingly, COVID-19 group had significantly higher levels for TNF-α (31.1 pg/ml [16.1–70.0] vs. 3.3 [1.8–9.6], P<0.001).The correlations between viral load/ tumor burden and various cytokine levels were shown in Figure 2. Lg viral loads were correlated with lg IL-6 (R2=0.101; P<0.001) and lg IL-10 (R2=0.105; P<0.001) .In CAR-T group, LDH was a common indicator related to tumor burden among patients with ALL, NHL, and MM. The lg LDH concentration was correlated with the lg serum concentration of IL-6 (R2=0.161; P=0.01). The independent risk factors for COVID-19-related sCRS were hypertension history (OR: 7.167, 95% CI: 2.345–21.903; P=0.001) and minimum platelets <100×109 /L during disease course (OR: 9.237, 95% CI: 2.544–33.546; P=0.001).

Conclusion：Our study demonstrated that there were similar processes but different intensity of inflammatory responses of sCRS in COVID-19 and CAR-T group. The diagnose and management of COVID-19 related sCRS can learn lessons from treatment of sCRS induced by CAR-T therapy.

Keywords: Cytokine release syndrome, COVID-19, Chimeric antigen receptor T-cell therapy

Disclosures: No relevant conflicts of interest to declare.

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