Most immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) resulted from excessive immune response against normal organs. The severity, timing, and organs affected by these events were often unpredictable. Adverse reactions could cause treatment delays or interruptions, in rare cases, pose a life-threatening risk. The mechanisms underlying irAE involved immune cell dysregulation, imbalances in inflammatory factor expression, alterations in autoantibodies and complement activation, even dysbiosis of intestinal microorganisms. However, the mechanisms of irAE occurrence might differ slightly among organs due to variations in their structures and the functions of resident immune cells. Future research should focus on the development of targeted drugs for the prevention or treatment of irAE based on the mechanisms by which irAE occurs in different organs. A deeper understanding of the mechanisms underlying irAE occurrence would aid clinicians in effectively utilizing ICIs and provide valuable guidance for their clinical application.
ObjectiveTo investigate the risk of myocarditis caused by immune checkpoint inhibitors (ICI). MethodsThe adverse reaction (ADR) reports on myocarditis caused by atelizumab, duvalizumab, pabolizumab, and navulizumab were downloaded from the FDA Adverse Event Reporting System (FAERS) from January 1, 2014 to September 30, 2022. The relevant analysis was conducted on the gender, age, medication dosage, and occurrence time of ICI related myocarditis patients. ResultsA total of 1 892 reports of myocarditis induced by ICI were included. The proportion of myocarditis caused by ICI was higher in males than in females (1.9∶1). The incidence of myocarditis in patients with basic diseases such as diabetes and heart disease, and in the age group 65-75 was relatively high. The incidence of myocarditis caused by navulizumab was high within 30 days with the use of conventional doses, and that of the other three drugs were high within 31 to 90 days. And the incidence of myocarditis is higher when used in combination than when used alone. ConclusionDifferent varieties of ICI can lead to the occurrence of myocarditis, and male, elderly, underlying diseases, and combination therapy may be risk factors for myocarditis caused by ICI.
Objective To systematically review the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy in the treatment of triple-negative breast cancer. Methods The PubMed, Cochrane Library, Embase, Web of Science, CNKI, WanFang Data and VIP databases were searched for randomised controlled trials (RCTs) of immune checkpoint inhibitors combined with chemotherapy versus chemotherapy alone for triple-negative breast cancer from inception to April 1, 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. Results A total of 13 RCTs involving 5 416 patients were included. The results of meta-analysis showed that the pathologic complete response rate (pCR) (OR=2.09, 95%CI 1.37 to 3.19, P<0.01), progression-free survival (PFS) (HR=0.75, 95%CI 0.67 to 0.83, P<0.01) and overall survival (OS) (HR=0.87, 95%CI 0.79 to 0.96, P<0.01) were significantly better than those in the control group. The results of subgroup analysis showed that there were statistically significant differences in PFS (P<0.01) and OS (P=0.02) between PD-L1-positive and PD-L1-negative patients, but there was no statistically significant difference in pCR between PD-L1-positive patients and PD-L1-negative patients (P=0.36). There was a statistically significant difference in pCR between node-positive patients and node-negative patients (P=0.03). There was no statistically significant difference in pCR between patients treated with PD-1 inhibitors and PD-L1 inhibitors (P=0.32); and there was no significant difference in PFS (P=0.19) or OS (P=0.99) between patients treated with PD-1 inhibitors and PD-L1 inhibitors. Compared with those in the control group, the incidences of serious adverse events (RR=1.36, 95%CI 1.09 to 1.70, P<0.01) and immune-related adverse events (RR=2.98, 95%CI 1.66 to 5.35, P<0.01) were higher in the experimental group, and the common immune-related adverse events were hypothyroidism and hyperthyroidism.Conclusion The existing evidence shows that immune checkpoint inhibitors combined with chemotherapy are more effective than chemotherapy alone in the treatment of triple-negative breast cancer, and the combination therapy has a higher incidence of adverse reactions. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
In December 2019, an outbreak of pneumonia associated with the coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. The lung imaging finding is like that of the lung cancer immune checkpoint inhibitors (ICI) associated pneumonia. Therefore, we speculated that they may have similar pathogenesis and treatment strategies, which is reviewed in this article in order to provide some reference to timely and effectively reduce the fatality rate of COVID-19.
Breast cancer is a malignancy with the highest incidence and mortality rate among women in the world. The current treatment methods include surgery, chemotherapy, radiotherapy, endocrine therapy and targeted therapy. Triple negative breast cancer (TNBC) has high manignant behavior and poor prognosis, lacks specific treatment targets, thus resulting in few effective treatment modalities. The emergence of immunotherapy has provided hopes for TNBC. The efficacy of immunocheckpoint inhibitors in neoadjuvant treatment of early TNBC and first-line treatment of programmed death-ligand 1 positive metastatic TNBC. Therefore, this article reviews the researches of immunocheckpoint inhibitors in the treatment of early and advanced breast cancer.
Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology by regulating the interaction between immune cells and cancer cells and promoting the disinhibition of the immune system, thus targeting various types of malignant tumors. However, the regulation of the immune system can also trigger related adverse reactions. Currently, there are no specific clinical guidelines for the treatment of these adverse reactions. Treatment decisions largely depend on clinical judgment and experience.The pathogenesis of ICI-related ocular adverse events is not fully understood at present. Further research on the specific mechanisms of action can provide new insights into the early diagnosis and treatment of ICI-related ocular adverse events.
ObjectiveTo investigate feasibility, safety, and problems to be solved in treatment with programmed death receptor protein-1 (PD-1) monoclonal antibody for patients with recurrent liver cancer after liver transplantation (LT).MethodAll of the domestic and foreign cases reports about the application of PD-1 monoclonal antibody in the patients with recurrent liver cancer after the LT were analyzed and summarized.ResultsIn six patients with recurrent liver cancer after the LT who received the PD-1 monoclonal antibody, the acute graft rejections were observed in 3 patients, 2 patients had the progressive disease but there was no evidence of the graft rejection, 1 patient achieved the complete response and there was no evidence of graft rejection and no side effects.ConclusionsAt present, effect of PD-1 monoclonal antibody therapy is still not sure in patients with recurrent liver cancer after LT. If PD-1 monoclonal antibody is used off-label, close surveillance is needed to discovery possible acute graft rejection.
Surgery remains as the primary definitive therapy for resectable non-small cell lung cancer (NSCLC) currently. However, quite a few NSCLC patients, especially in the later stage, suffered tumor recurrence after resection. Safer and more effective perioperative treatment is urgently needed to reduce the recurrence risk after NSCLC surgery. Immune checkpoint inhibitors can effectively prevent tumor immune evasion and have been shown to be a feasible, safe and effective neoadjuvant therapy for resectable NSCLC. Nevertheless, certain crucial problems, including the final effect on NSCLC recurrence, the selection of beneficial group and optimal treatment protocol are yet unsolved. Fortunately, several phase Ⅲ randomized controlled trials are ongoing to answer these questions and will hopefully provide stronger evidence.
Objective To investigate the prediction of baseline neutrophil-lymphocyte ratio (NLR) on the prognosis of unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) + lenvatinib + camrelizumab. Method The clinical data of 58 patients treated with TACE + lenvatinib + camrelizumab in the Department of Liver Surgery of West China Hospital of Sichuan University from June 2020 to May 2021 were analyzed retrospectively. Results Among the 58 cases included, 7 cases were complete response (CR), 37 cases were partial response (PR), 11 cases were stable disease (SD), and 3 cases were progressive disease (PD). All cases had different degrees of adverse events, including 58 cases of grade 1, 36 cases of grade 2, 35 cases of grade 3, and 1 case of grade 4. The overall response rate (ORR) and disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) were 75.9% (44/58) and 94.8% (55/58), respectively. The hepatectomy rate was 31.0% (18/58) and the conversion success rate was 37.9% (22/58). Multivariate logistic regression analysis showed that NLR was an independent risk factor for ORR (OR=0.093, P=0.008). All cases were followed up for 16–60 weeks, with a median follow-up of 34 weeks. Overall survival situation (χ2=4.163, P=0.041) and progression free survival situation (χ2=10.626, P=0.001) in the low NLR group were better than those of the high NLR group. Conclusion NLR has clinical significance in predicting the prognosis of uHCC cases underwent TACE + lenvatinib + camrelizumab, which is worthy of further study.