Tocilizumab and immune signatures for targeted management of cytokine release syndrome in immune checkpoint therapy.

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2024-12-17 DOI:10.1016/j.annonc.2024.12.004

D Daoudlarian, A Segot, S Latifyan, R Bartolini, V Joo, N Mederos, H Bouchaab, R Demicheli, K Abdelhamid, N Ferahta, J Doms, G Stalder, A Noto, L Mencarelli, V Mosimann, D Berthold, A Stravodimou, C Sartori, K Shabafrouz, J A Thompson, Y Wang, S Peters, G Pantaleo, M Obeid

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引用次数: 0

Abstract

Background: This study aimed to identify specific biomarkers in oncology patients experiencing immune-related cytokine release syndrome (irCRS)-like symptoms during immune checkpoint inhibitor (ICI) therapy, including severe cases like hemophagocytic lymphohistiocytosis (irHLH), and to distinguish these from sepsis. A secondary objective was to retrospectively analyze the efficacy of tocilizumab (TCZ) in treating corticosteroid (CS)-refractory high-grade irCRS.

Patients and methods: A cohort of 35 patients presenting with irCRS-like symptoms was studied, including 9 with irHLH-like manifestations and 8 with sepsis. Immune profiling was performed using 48 mass cytometry markers, along with an analysis of 45 serum biomarkers, including 27 cytokines and 18 additional markers from the HScore. Twelve patients with high-grade irCRS refractory to CS were treated with TCZ.

Results: 24 biomarkers significantly distinguished between irHLH and Grade 3 irCRS (P=0.0027-0.0455). Hepatocyte growth factor (HGF) and ferritin had superior predictive values compared to the traditional HScore, both with a positive predictive value (PPV) and negative predictive value (NPV) of 100%. CXCL9 differentiated irHLH from Grade 3 irCRS and predicted the need for TCZ treatment intensification (PPV=90%, NPV=100%). Additional biomarkers, including leukocyte count, neutrophils, ferritin, IL-6, IL-7, EGF, fibrinogen, and GM-CSF, discriminated sepsis from high-grade irCRS (PPV=75-80%, NPV=100%). Elevated frequencies of CXCR5+ or CCR4+ CD8 memory cells, CD38+ intermediate monocytes, and CD62L+ neutrophils were observed in high-grade irCRS compared to sepsis. All 12 patients with high-grade irCRS refractory to CS treated with TCZ experienced complete resolution.

Conclusions: This study highlights the importance of specific immunologic biomarkers in determining irCRS severity, predicting outcomes, and distinguishing between irHLH, irCRS, and sepsis. It also demonstrates the efficacy of TCZ in managing high-grade irCRS, underscoring the need for personalized therapeutic strategies based on these biomarkers.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.