Tumor immunotherapy includes immune checkpoint inhibitor (ICI), tumor vaccines, and adoptive cell therapy. Immunotherapy, as the main systemic treatment for advanced malignant tumors, kills tumor cells by activating the immune system and prolongs the survival of patients. However, excessive immune responses can cause immune-related adverse events (irAE), causing damage to systemic tissues. ICI are the main tumor immunotherapy drugs that cause optic nerve irAE. The most common optic nerve irAE are optic neuritis, only a few patients appeared arteritic anterior ischemic optic neuropathy. Sudden painless loss of bilateral vision is the most common clinical manifestation. In severe cases, the vision decrease to no light perception. Early diagnosis and early adequate glucocorticoid treatment can improve the symptoms. Therefore, neuro-ophthalmologists and oncologists should know the clinical characteristics of optic nerve irAE, in order to diagnose and treat early and improve the prognosis.
Objective To analyze the clinical features of immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer. Methods The case data of patients with CIP admitted to Zhongshan Hospital of Fudan University from January 2017 to December 2020 were retrospectively collected, and the basic data, clinical manifestations, imaging data, laboratory examination results, treatment and prognosis of the patients were analyzed. Results The ratio of male to female was 18:1, and the median age was 65 years (from 41 to 74 years). Fourteen patients received a programmed death protein-1 (PD-1) inhibitor and five patients received a programmed death protein-ligand-1 (PD-L1) inhibitor. The median time to CIP was 3.5 months. The respiratory symptoms of 15 patients were dyspnea in 11 cases, cough in 9 cases, chest tightness in 8 cases, fever in 4 cases, expectoration in 4 cases and hemoptysis in 2 cases. Chest CT findings mainly showed interstitial pneumonia, including 8 cases of implicit organizational pneumonia (COP), 7 cases of non-specific interstitial pneumonia (NSIP), 2 cases of acute interstitial pneumonia, and 2 cases of allergic pneumonia. C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase were higher in CIP than before, and the difference was statistically significant. Follow-up observation was performed in 3 patients alone, 14 patients were treated with glucocorticoid alone, 2 patients were treated with immunosuppressant therapy, 19 patients had stable or more absorption of pneumonia lesions, and 5 patients had restarted immunotherapy. There were no deaths from CIP. Conclusions CIP mainly occurs in men, with slow onset, lack of specificity in clinical manifestations, and increased inflammatory indicators. Imaging findings are mainly NSIP and COP changes. Early identification, diagnosis and rational application of glucocorticoid therapy have good effects.
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 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.
Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis. Methods Computerized retrieval of PubMed, EMbase, Web of Science, the Cochrane Library , WanFang Data, CNKI and VIP databases was carried out. Studies were collected from the database establishment to March 2023. Three researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.4.1software. Results A total of 18 studies were included with a total of 4 990 patients. The results of meta-analysis showed that, interstitial pneumonia [odds ratio (OR)=9.32, 95% confidence interval (CI) 4.66 - 18.67, P<0.01], smoking history (OR=2.39, 95%CI 1.29 - 4.45, P<0.01), chronic obstructive pulmonary disease (COPD) (OR=5.54, 95%CI 2.96 - 10.36, P<0.01), chest radiotherapy (OR=2.74, 95%CI 1.80 - 4.19, P<0.01), pulmonary fibrosis (OR=7.46, 95%CI 4.25 - 13.09, P<0.01), high programmed death ligand 1 (PD-L1) expression (OR=2.98, 95%CI 1.71 - 5.22, P<0.01), high absolute eosinophil count (AEC) (OR=3.92, 95%CI 2.17 - 7.08, P<0.01) and pembrolizumab (OR=2.90, 95%CI 1.56 - 5.37, P<0.01) were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Conclusions Interstitial pneumonia, smoking history, COPD, Chest radiotherapy, pulmonary fibrosis, high PD-L1expression, high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Due to insufficient evidence on the risk factors of low albumin, more studies are needed to further identify it.
The treatment of patients with advanced lung cancer has been revolutionized with the advent of immunotherapy. However, not all patients can benefit equally from immunotherapy. In recent years, the relationship between intestinal flora and the efficacy of immunotherapy has gradually attracted scholars' attention. During the treatment of immune checkpoint inhibitors, the use of antibiotics, proton pump inhibitors and other drugs will affect the patient's intestinal flora, thus affecting the efficacy of immune checkpoint inhibitors, leading to poor prognosis of patients. This review will discuss that antibiotics and proton pump inhibitors reduce the efficacy of immunotherapy by affecting the diversity of intestinal flora, in order to facilitate the rational use of related drugs in clinical practice and improve the patient's outcomes.
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.