Immunotherapy最新文献

Cytokine release syndrome (CRS) is an uncommon but deadly side effect of immune checkpoint inhibitors (ICIs). ICIs are presently an increasingly important therapy option for malignant tumors, but there are limited treatments available for CRS. We present a case of a 72-year-old man who received one cycle of ICI coupled with cisplatin and albumin-binding paclitaxel therapy for a locally advanced right lung adenocarcinoma. Following an abrupt onset of dyspnea, the patient underwent a quick physical examination, blood tests and was diagnosed with CRS. After prompt initiation of glucocorticoid pulse treatment, the symptoms relieved. The case illustrates the management of severe CRS following ICI therapy while highlighting the uncommon and potentially fatal immune-related side effects.

Background: Patients with moderate-to-severe rheumatoid arthritis (RA) in China experience multi-system dysfunction, resulting in a substantial economic burden. This study aimed to compare the cost-effectiveness of Upadacitinib and Tofacitinib as treatment options for moderate-to-severe RA patients in China.

Materials and methods: A Decision Tree-Markov model with a 24-week cycle was constructed, simulating health status transitions based on the tsDMARDs-TNFi-PC clinical pathway. The analysis included the calculation of treatment costs (yuan) and QALYs (quality-adjusted life-years) for the Upadacitinib and Tofacitinib groups. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER) and compared against a willingness-to-pay (WTP) threshold. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to verify the robustness of the results.

Results: Compared with Tofacitinib, the Upadacitinib group incurred an additional cost of 1,375 yuan per patient, with an incremental gain of 0.17 QALYs. The ICER was 7,880.38 yuan/QALY, which is well below the WTP threshold of 1.5 times China's GDP per capita, indicating favorable cost-effectiveness.

Conclusions: In the context of China's healthcare system, Upadacitinib represents a cost-effective long-term first-line treatment option for moderate-to-severe RA patients.

Circulating tumor DNA (ctDNA) represents a powerful measure of minimal residual disease (MRD) in colorectal cancer (CRC). Although immunotherapy has been widely established in metastatic CRC that is mismatch repair deficient or microsatellite instability-high (dMMR/MSI-H), its role in non-metastatic CRC is rapidly evolving. In resected, dMMR/MSI-H stage II CRC, adjuvant fluoropyrimidine has no benefit and is not recommended. There is growing evidence to suggest diminished benefit from neoadjuvant chemotherapy and chemoradiation in localized CRC that is dMMR/MSI-H. We present two cases of dMMR/MSI-H stage III CRC treated with definitive surgery wherein adjuvant oxaliplatin-based chemotherapy led to a failure to clear postoperative plasma ctDNA levels, prompting a change to immune checkpoint blockade with pembrolizumab and resultant ctDNA clearance. We illustrate that chemotherapy may achieve suboptimal disease control in localized colon cancer that is dMMR/MSI-H, while plasma ctDNA offers a window of opportunity to gauge the efficacy of oxaliplatin-based adjuvant chemotherapy to clear microscopic disease in resected, dMMR/MSI-H stage III colon cancer. These findings are important to contextualize given that relapse is inevitable with failure to clear MRD in the postoperative stage I-III CRC setting whereby chemotherapy remains the standard adjuvant therapy in resected, dMMR/MSI-H stage III colon cancer.

Immune checkpoint inhibitors (ICIs) related myocarditis is a rare complication of modern immunotherapy. It can present as an asymptomatic subclinical condition or full-blown fulminant myocarditis with malignant arrythmias and cardiogenic shock. Myositis/rhabdomyolysis and/or myasthenic symptoms can be present concomitantly. We present a case of fatal fulminant myocarditis presenting with cardiac arrythmias and severe systolic dysfunction, with accompanying rhabdomyolysis after the first dose of ipilimumab and nivolumab immunotherapy. First working diagnosis of subacute late presenting acute myocardial infarction (ACS) was incorrect and the correct diagnosis was established only after additional testing and consultation. Treatment consisted of high-dose corticosteroids, intravenous immunoglobulins, sedation with mechanical ventilation, antibiotic coverage, hemodialysis, and sustained low-efficiency daily diafiltration (SLEDD) with CytoSorb or TheraNova membranes, and intra-aortic balloon pump mechanical cardiac support. No tangible improvement in the condition was observed during the whole treatment period and the patient died on the sixth day of intensive care treatment.

With the advent of chimeric antigen receptors T-cell therapy, understanding their role in the development of hemophagocytic lymphohistiocytosis has become increasingly complex. We describe a case of a young patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma, who was treated with axicabtagene ciloleucel. The patient developed progressive cytopenia and, on Day 73 post-infusion, met criteria for hemophagocytic lymphohistiocytosis. Bone marrow evaluation revealed hemophagocytosis without evidence of clonal B cells. The patient was treated with tocilizumab, dexamethasone, etoposide and anakinra, which eventually led to improvement. Unfortunately, the patient succumbed to an infection. Disease progression was confirmed posthumously.This case report explores the differential diagnosis of hyperinflammatory syndromes following chimeric antigen receptor T-cell therapy and highlights the reduced efficacy of this treatment in patients with a T-cell/histiocyte-rich background.

Allergen immunotherapy is a disease-modifying treatment for allergic diseases. The predominant traditional immunotherapy is through subcutaneous administration of allergens to gradually desensitize allergic individuals. While effective, traditional allergen immunotherapy approaches are often lengthy, time consuming for patients and can result in local or systemic adverse reactions. Nontraditional immunotherapies are emerging as promising alternatives, offering potentially more convenient, safe and efficacious treatment options. This review sought to comprehensively examine the safety, efficacy and performance of various nontraditional immunotherapies for environmental allergens. Nontraditional immunotherapy approaches covered in this review include sublingual, local nasal, intralymphatic rush and ultra-rush immunotherapy, allergoid, microbial and anti-IgE immunotherapies. Nontraditional immunotherapies show significant promise in addressing the limitations of traditional subcutaneous immunotherapy. Methods like intralymphatic and rush immunotherapy offer shorter treatment regimens, enhancing patient adherence and convenience. The co-administration of probiotics or monoclonal antibodies, like omalizumab, with AIT appears to improve treatment efficacy and safety. Despite these advancements, further large-scale, long-term studies are needed to establish standardized protocols, dosing and validate long-term effects of these nontraditional immunotherapies. Standardizing outcome measurements across studies is crucial for accurate comparisons of nontraditional immunotherapies prior to widespread clinical adoption of these innovative techniques.