Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67-year-old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein-1 (PD-1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL-6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune-related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin-related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD-1 inhibitor was administered. In addition, this apparent severe oxaliplatin-related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.

UNASSIGNED: To describe cytokine release syndrome (CRS) associated with immune checkpoint inhibitors (ICIs) reported in the FDA Adverse Event Reporting System (FAERS).
UNASSIGNED: We obtained ICIs adverse event (AE) reports from January 2011 to September 2023 from the FAERS database. The preferred term (PT) \'cytokine release syndrome\' from the Medical Dictionary for Regulatory Activities (MedDRA) 26.1 was used to identify cases with ICIs-related CRS. The reporting odds ratio (ROR) of the disproportionality method was performed to quantify the association between CRS and ICIs treatment strategy.
UNASSIGNED: Three hundred and ninety-five cases were gathered. 42.03% of the patients were aged 18 to 65. Male patients outnumbered female patients (53.67% vs. 34.94%). The prevalent potential cancer types were lung cancer (33.42%) and skin cancer (20.51%). Japanese were responsible for the majority of ICIs-related CRS cases (176 cases). The combination of nivolumab and ipilimumab resulted in the most CRS cases (138 cases), and the ICIs combination therapy had the highest ROR signal value (ROR = 11.95 [10.14-14.06]). ICIs-related CRS had a median time to onset of 14 days (interquartile range [IQR] 7-43.25).
UNASSIGNED: ICIs-related CRS is an increasingly important immune-related AE. Our study provided helpful information to help medical professionals learn more about ICIs-related CRS.

BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events.
METHODS: This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes.
CONCLUSIONS: Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

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.

As indications for immune checkpoint inhibitors for breast cancer continue to expand, rare toxicities will emerge that require careful consideration and multidisciplinary management. We report the case of a 40-year-old female receiving neoadjuvant pembrolizumab and chemotherapy for locally advanced triple-negative breast cancer who developed cytokine release syndrome (CRS)/hemophagocytic lymphohistiocytosis (HLH). CRS/HLH secondary to pembrolizumab are scarcely documented in the literature and, to our knowledge, have never been reported in the context of neoadjuvant treatment for breast cancer.

Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC-1 study. Cytokines, especially interleukin (IL)-6, are known suppressors of cytochrome P450 (CYP) enzymes\' activity. A physiologically based pharmacokinetic model evaluated the impact of IL-6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL-6 kinetics profiles were assessed, the mean IL-6 profile with a maximum concentration (Cmax) of IL-6 (21 pg/mL) and the IL-6 profile of the patient presenting the highest IL-6 Cmax (288 pg/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC-1. For the mean IL-6 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87-1.20). For the maximum IL-6 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90-2.23), and minimal for caffeine and s-warfarin (mean AUC ratios 0.82-1.25). Maximum change in exposure for these substrates occurred 3-4 days after step-up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL-6 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step-up dosing up to 7 days after the first treatment dose (1.5 mg/kg subcutaneously) and during and after CRS.

Cytokine release syndrome (CRS) is a systemic inflammatory condition caused by an excessive immune response and cytokine overproduction. CRS is a life-threatening condition that is often associated with chimeric antigen receptor T-cell therapy. Despite the increased use of immune checkpoint inhibitors (ICIs), ICI-induced CRS remains rare. The present study describes a case of CRS that occurred after the administration of ICIs for recurrent adenocarcinoma of the uterine cervix. A 49-year-old woman received paclitaxel, carboplatin and pembrolizumab for recurrent cervical adenocarcinoma. On day 27 of the third cycle, the patient was admitted with a fever and suspected pyelonephritis. The following day, hypotension, upper respiratory symptoms and myalgia of the extremities were noted, and the left ventricular ejection fraction (LVEF) was decreased to 20%. Multiorgan failure (MOF) occurred, and the patient received ventilator support and continuous hemodiafiltration. Rhabdomyolysis, pancreatitis, erythema multiforme and enteritis were observed. CRS was diagnosed based on elevated ferritin and IL-6 levels. Steroid pulse therapy was administered; however, the MOF did not improve and the anti-IL-6-receptor monoclonal antibody tocilizumab (TOC) was administered. Subsequently, the LVEF improved to 50%, and the patient was removed from the ventilator on day 4 and from the continuous hemodiafiltration unit on day 6 after TOC administration. The patient was discharged on day 21. In conclusion, considering that ICI-induced CRS is a rare but severe complication, fever and other systemic conditions following ICI administration should be monitored.

BACKGROUND CRS (cytokine release syndrome) is a massive activation of the inflammatory system characterized by a supra-physiological rate of inflammatory cytokines. The interleukin 6 cytokine plays a central role in CRS. The main clinical sign of CRS is fever, but CRS can lead to multiple organ failure in severe cases. CRS is usually described in sepsis, more recently in SARS COV-2 infection, and in chimeric antigen receptor T-cell therapy. However, it can also be associated with immune checkpoint inhibitors (ICIs), which is infrequently described. ICI have growing indications and can lead to CRS by causing an uncontrolled activation of the immune system. There are currently no treatment guidelines for ICI-induced CRS. CASE REPORT We report a rare case of grade 3 CRS induced by nivolumab associated with 5-fluorouracil and oxaliplatin for gastric cancer. The patient was 65-year-old man with an adenocarcinoma of the cardia. CRS developed during the tenth course of treatment and was characterized by fever, hypotension requiring vasopressors, hypoxemia, acute kidney injury, and thrombopenia. The patient was transferred quickly to the Intensive Care Unit. He was treated for suspected sepsis, but it was ruled out after multiple laboratory examinations. There was rapid resolution after infusion of hydrocortisone. CONCLUSIONS The use of ICIs is expanding. Nivolumab-induced CRS is rarely described but can be severe and lead to multiple organ dysfunction; therefore, intensive care practitioners should be informed about this adverse effect. More studies are needed to better understand this condition and establish treatment guidelines.

Introduction: Our case is unique because the differential diagnosis was a challenge. At first, the patient presented with septic shock and multi-organ failure in the context of a suspected lymphoproliferative syndrome. Once the lymphoproliferative process had been ruled out, hemophagocytic syndrome due to COVID-19 infection was suspected, so he is probably one of the few patients with such an exhaustive study that could contribute to our understanding of COVID-19. We followed therapeutic guidelines that differ from the usual, using adrenalin and levosimendan. Corticosteroids helped to modulate the cytokine storm. Case report: A 16-year-old adolescent was admitted to the intensive care unit with fever, diarrhea, multiorgan failure and septic shock. He was IgG positive for COVID-19 and IgM negative. Thoraco-abdominal computed tomography demonstrated multiple para-aortic and peri-pancreatic lymphadenopathy and acute respiratory distress syndrome. The first suspected diagnosis was a lymphoproliferative syndrome and bacterial infection. The second possibility was a hemophagocytic syndrome in a patient recovering from COVID-19. He was treated with broad spectrum antibiotics because the differential diagnosis was difficult, and we removed them when the microbiological screening was negative. During the course of the disease he presented with severe biventricular dysfunction, probably due to the cytokine storm, so we used inotropic drugs (adrenaline, levosimendan). Infection with Salmonella species group B was diagnosed later, when the patient was in the Internal Medicine ward, although he was asymptomatic. Conclusion: The severity of COVID-19 infection ranges from mild to severe, causing serious disease in some people. Although the pathophysiology is not well known, it seems that in some cases an immune storm is triggered, and it is related to more serious and prolonged disease. In our case, heart failure was important, because it could have worsened the prognosis. Fortunately, the response to levosimendan and corticosteroids was adequate and he recovered favorably until discharge.

BACKGROUND: Cytokine storm is now considered to be a systemic inflammatory response, but local cytokine storm may exist in systemic diseases of the blood system. Monitoring of regional cytokine storm is an important clue for the diagnosis of systemic diseases.
METHODS: A 72-years-old male presented to our hospital with multiple serosal effusion without solid mass or enlarged lymph nodes. We found that the level of cytokines in ascites was tens to hundreds of times higher than that in plasma, mainly IL-6 and IL-8.
METHODS: The patient was diagnosed with multiple serous effusion, hemophagocytic syndrome, B-cell lymphoma, Epstein-Barr virus infection, and hypoproteinemia.
METHODS: During hospitalization, the patient was treated with 5 courses of R-CVEP therapy and supportive treatment.
RESULTS: After the first R-CVEP regimen, the patient\'s condition was evaluated as follows: hemophagocytic syndrome improved: no fever; Serum triglyceride 2.36 mmol/L; Ferritin 70.70 ng/L; no hemophagocyte was found in the bone marrow; the lymphoma was relieved, ascites disappeared, and bone marrow cytology showed: the bone marrow hyperplasia was reduced, and small platelet clusters were easily seen. Bone marrow flow cytometry showed that lymphocytes accounted for 13.7%, T cells increased for 85.7%, CD4/CD8 = 0.63, B cells decreased significantly for 0.27%, and NK cells accounted for 10.2%. Blood routine returned to normal: WBC 5.27 × 109/L, HB 128 g/L, PLT 129 × 109/L; Epstein-Barr virus DNA < 5.2E + 02 copies/mL; correction of hypoproteinemia: albumin 39.7 g/L.
CONCLUSIONS: Cytokines in ascites are significantly higher than those in plasma by tens to hundreds of times, suggesting that \"regional cytokine storms\" may cause serosal effusion.