Cytokine release syndrome (CRS) is a systemic inflammatory syndrome that causes fatal circulatory failure due to hypercytokinemia, and subsequent immune cell hyperactivation caused by therapeutic agents, pathogens, cancers, and autoimmune diseases. In recent years, CRS has emerged as a rare, but significant, immune-related adverse event linked to immune checkpoint inhibitor therapy. Furthermore, several previous studies suggested that damage-associated molecular patterns (DAMPs) could be involved in malignancy-related CRS. In this study, we present a case of severe CRS following combination therapy with durvalumab and tremelimumab for advanced hepatocellular carcinoma, which recurred during treatment, as well as an analysis of cytokine and DAMPs trends. A 35-year-old woman diagnosed with hepatocellular carcinoma underwent a partial hepatectomy. Due to cancer recurrence, she started a combination of durvalumab and tremelimumab. Then, 29 days post-administration, she developed fever and headache, initially suspected as sepsis. Despite antibiotics, her condition worsened, leading to disseminated intravascular coagulation and hemophagocytic syndrome. The clinical course and elevated serum interleukin-6 levels led to a CRS diagnosis. Steroid pulse therapy was administered, resulting in temporary improvement. However, she relapsed with increased interleukin-6, prompting tocilizumab treatment. Her condition improved, and she was discharged on day 22. Measurements of inflammatory cytokines interferon-γ, tumor necrosis factor-α, and DAMPs, along with interleukin-6, using preserved serum samples, confirmed marked elevation at CRS onset. CRS can occur after the administration of any immune checkpoint inhibitor, with the most likely trigger being the release of DAMPs associated with tumor collapse.
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http://dx.doi.org/10.1111/hepr.14088 | DOI Listing |
Br J Clin Pharmacol
December 2024
School of Public Health, Fudan University, Shanghai, People's Republic of China.
Aims: To examine the cost-effectiveness of first-line systemic therapies recommended by the National Comprehensive Cancer Network guidelines for Unresectable Hepatocellular Carcinoma (uHCC) from the US social and payer's perspective.
Methods: A cost-effectiveness analysis was conducted using a three-state partitioned survival model to assess the cost-effectiveness of atezolizumab plus bevacizumab, tremelimumab plus durvalumab, durvalumab, lenvatinib and sorafenib as first-line treatments for uHCC. Clinical efficacy was derived from a published network meta-analysis.
Cancers (Basel)
December 2024
Department of Oncological Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland.
Hepatocellular carcinoma (HCC) is a prevalent malignant tumour worldwide. Depending on the stage of the tumour and liver function, a variety of treatment options are indicated. Traditional radiotherapy and chemotherapy are ineffective against HCC; however, the U.
View Article and Find Full Text PDFCancers (Basel)
November 2024
Medicine and Oncology ISU, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA.
Hepatocellular carcinoma (HCC), a liver cancer originating from hepatocytes, is a major health concern and among the most common malignancies worldwide. Sorafenib, approved by the U.S.
View Article and Find Full Text PDFAdv Ther
December 2024
Source Health Economics, London, UK.
Introduction: This study compared the relative efficacy of first-line lenvatinib, a standard-of-care treatment for unresectable hepatocellular carcinoma (uHCC), vs licensed/license in-progress comparators. Using inverse probability of treatment weighting (IPTW) and network meta-analysis (NMA), updated evidence for lenvatinib monotherapy from LEAP-002, in addition to evidence from REFLECT, was included in the analyses.
Methods: Randomized controlled trials (RCTs) were identified via systematic review.
Radiol Med
December 2024
Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
Purpose: The aim of this study was to assess the feasibility of quantifying morphologic changes in tumors during immunotherapy, as a reflection of response or survival.
Methods And Materials: A retrospective single-center analysis was performed in patients with unresectable liver cancer previously enrolled in clinical trials combining immunotherapy (tremelimumab ± durvalumab) and locoregional treatment (either ablation or transarterial chemoembolization). Conventional response (RECIST 1.
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