Identifying Early Infections in the Setting of CRS with Routine and Exploratory Serum Proteomics and the HT10 Score Following CD19 CAR-T for Relapsed/Refractory B-NHL

Rejeski K, Blumenberg V, Iacoboni G, Lopez-Corral L, Kharboutli S, Hernani R, Petrera A, Müller N, Hildebrand F, Frölich L, Karschnia P, Schmidt C, Cordas Dos Santos DM, Piñana JL, Müller F, Martin AA, Dreyling M, Von Bergwelt-Baildon M, Barba P, Subklewe M, Bücklein VL (2023)

Publication Type: Journal article

Publication year: 2023

Journal

HemaSphere Lippincott, Williams & Wilkins

Book Volume: 7

Pages Range: E858-

Journal Issue: 4

DOI: 10.1097/HS9.0000000000000858

Abstract

Early fever after chimeric antigen receptor T-cell (CAR-T) therapy can reflect both an infection or cytokine release syndrome (CRS). Identifying early infections in the setting of CRS and neutropenia represents an unresolved clinical challenge. In this retrospective observational analysis, early fever events (day 0-30) were characterized as infection versus CRS in 62 patients treated with standard-of-care CD19.CAR-T for relapsed/refractory B-cell non-Hodgkin lymphoma. Routine serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], procalcitonin [PCT]) were recorded daily. Exploratory plasma proteomics were performed longitudinally in 52 patients using a multiplex proximity extension assay (Olink proteomics). Compared with the CRSonlycohort, we noted increased event-day IL-6 (median 2243 versus 64 pg/mL, P = 0.03) and particularly high PCT levels (median 1.6 versus 0.3 µg/L, P < 0.0001) in the patients that developed severe infections. For PCT, an optimal discriminatory threshold of 1.5 µg/L was established (area under the receiver operating characteristic curve [AUCROC] = 0.78). Next, we incorporated day-of-fever PCT levels with the patient-individual CAR-HEMATOTOX score. In a multicenter validation cohort (n = 125), we confirmed the discriminatory capacity of this so-called HT10 score for early infections at first fever (AUCROC= 0.87, P < 0.0001, sens. 86%, spec. 86%). Additionally, Olink proteomics revealed pronounced immune dysregulation and endothelial dysfunction in patients with severe infections as evidenced by an increased ANGPT2/1 ratio and an altered CD40/CD40L-axis. In conclusion, the high discriminatory capacity of the HT10 score for infections highlights the advantage of dynamic risk assessment and supports the incorporation of PCT into routine inflammatory panels. Candidate markers from Olink proteomics may further refine risk-stratification. If validated prospectively, the score will enable risk-adapted decisions on antibiotic use.

Involved external institutions

Klinikum der Universität München DE Germany (DE) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Complejo Hospitalario de Salamanca / Complejo Asistencial Universitario de Salamanca ES Spain (ES) Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE) Hospital Clínico Universitario de Valencia ES Spain (ES) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Rejeski, K., Blumenberg, V., Iacoboni, G., Lopez-Corral, L., Kharboutli, S., Hernani, R.,... Bücklein, V.L. (2023). Identifying Early Infections in the Setting of CRS with Routine and Exploratory Serum Proteomics and the HT10 Score Following CD19 CAR-T for Relapsed/Refractory B-NHL. HemaSphere, 7(4), E858-. https://doi.org/10.1097/HS9.0000000000000858

MLA:

Rejeski, Kai, et al. "Identifying Early Infections in the Setting of CRS with Routine and Exploratory Serum Proteomics and the HT10 Score Following CD19 CAR-T for Relapsed/Refractory B-NHL." HemaSphere 7.4 (2023): E858-.

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