Project description:BackgroundImmune checkpoint inhibitors (ICIs) in the setting of liver transplant (LT) pose a risk of rejection and hold unclear benefit in both the neoadjuvant (pre-transplant) and post-transplant salvage setting. In the pre-transplant setting, neoadjuvant ICIs may serve as a bridge to LT by downstaging disease burden to fit within transplant criteria. Outcomes in this setting include patients who had successful transplants without complications to patients who suffered severe complications, including fatal hepatic necrosis and graft failure requiring re-transplant. Some authors suggest having a period of three months between checkpoint inhibition and transplant may help mitigate adverse effects. In the post-LT setting, there are few treatment options if there is a recurrence of disease, which forces treatment teams to reconsider checkpoint inhibitors. Again, a longer period of time between transplant and checkpoint inhibition may reduce risk of rejection. Case reports of patients treated with ICIs post-transplant utilized either nivolumab or pembrolizumab. As combination atezolizumab/bevacizumab is a relatively new treatment option for unresectable hepatocellular carcinoma (HCC), there are only three reported cases using this combination in the post-LT setting. While there were no cases of rejection, all three cases had progression of disease. As immunotherapy joins transplantation as a mainstay of treatment for HCC, it remains unclear how to best navigate when the treatment course involves both immune activation and immunosuppression.Case descriptionPatients who had an LT and were treated with ICIs (pre or post LT) at the University of Cincinnati were included in this retrospective chart review.ConclusionsFatal rejection remains a significant risk even 4 years after LT. Neoadjuvant ICIs also pose a risk for acute cellular rejection; however, this may not always be clinically significant. Graft versus host disease (GVHD) may be an additional, previously unreported risk of ICIs in the setting of LT. Prospective studies are needed to understand benefits and risks of checkpoint inhibitors in the LT setting.

Project description:BackgroundAngiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas.MethodsWe performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue.ResultsWe have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities.ConclusionsThis case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.

Project description:Background and Objective: Immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors may have synergistic effects in elderly patients with advanced driver-negative NSCLC, but its true efficacy remains unclear. In addition, chemotherapy tolerance in elderly NSCLC patients is poor, and the precise identification of the population that may benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC ≥65 years of age in the Cancer Center of Suzhou Hospital Affiliated to Nanjing Medical University. The primary endpoint was PFS. Secondary endpoints were OS, ORR, and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group (immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group (immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in the IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group (8.1 months vs 5.3 months; HR for PFS: 0.778, 95%CI: 0.474-1.276, P=0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P=0.519). There were no significant differences in median PFS and median OS between the two groups. Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P=0.017), and the association between different groups and disease progression was still different in the two subgroups (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P=0.465). The incidence of irAEs in the IA group was lower than that in the NIA group (39.5% vs 19.4%, P=0.05), and the cumulative incidence of treatment interruptions due to irAEs was significantly reduced (P=0.045). Conclusion: In elderly patients with advanced driver-negative NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of irAEs and treatment interruptions due to irAEs was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration.

Project description:BackgroundAntinuclear antibodies (ANAs) predicting the safety and efficacy of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate considering previous studies showed quite different results based on different ANA cut-off values. Thus, we investigated the associations between different ANA titers and the safety and efficacy of ICIs. Moreover, we also briefly discussed the effects of anti-thyroglobulin (ATG) and anti-thyroid peroxidase (ATPO) on the safety of ICIs.MethodsA total of 159 Chinese patients confirmed to have locally-advanced or metastatic NSCLC given ICIs or chemoimmunotherapy in Peking Union Medical College Hospital from January 2015 to December 2020 were analyzed retrospectively and were followed up until December 2020 or death or loss to follow-up. Patients' characteristics were retrieved from medical records. ANAs were detected by the indirect immunofluorescence assay, ATG and ATPO by the electrochemiluminescence immunoassay. The severity of immune-related adverse events (irAEs) was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) and the efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).ResultsThe incidence of irAEs, median progression-free survival (mPFS) of the ANA negative and positive groups were 26.0% vs. 31.4% (P=0.457), 17.7 vs. 10 months (P=0.603) for the cut-off value of 1:80; 26.2% vs. 33.9% (P=0.305), 11.9 vs. 10.6 months (P=0.957) for 1:160; and 25.9% vs. 45.8% (P=0.047), and 11.9 vs. 7.7 months (P=0.471) for 1:320, separately. Besides, ANA titer ≥1:320 was associated with irAEs [odds ratio (OR) =4.9, 95% confidence interval (CI): 1.45-16.52, P=0.01] and the incidence of adverse skin reactions differed greatly between the negative and positive groups (9.7% vs. 32%, P=0.003). Moreover, a total of 52 out of 159 patients were tested for ATG and ATPO. 46 patients were negative and 6 were positive, with the incidence of abnormal thyroid function being 4.3% vs. 50% (P=0.005), respectively.ConclusionsPreexisting ANAs may not correlate with the clinical benefit of immunotherapy in patients with NSCLC but may be associated with adverse skin reactions. Besides, ATG or ATPO has the potential to predict thyroid dysfunction.

Project description:BACKGROUND:Since 2012, several immune checkpoint inhibitors have been approved by the Taiwan FDA for various types of cancer treatment. However, none of them are covered by Taiwan National Health Insurance due to the fact that they are expensive, and there is a lack of clinical evidence as to their effectiveness. OBJECTIVES:This study was aimed toward an exploration of clinical experiences with use of immune checkpoint inhibitors, including indications, prescription types, drug effectiveness, adverse drug event types, and incidence, all of which shall serve as references for future clinical drug use. METHODS:This is a retrospective study focusing on three immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab), which are available for cancer treatment in Taiwan. We collected data from medical records for the period from January 1st, 2015 to January 12th, 2017 at National Cheng Kung University Hospital (NCKUH), a medical center in southern Taiwan, and recorded these cases until May 31st, 2017. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and adverse drug reaction odds ratios were analyzed using a chi-square analysis. RESULTS:The 50 patients under consideration in this study had used any one of the immune checkpoint inhibitors in NCKUH. Non-small cell lung cancer (n = 24, 48%) accounted for the highest percentage, followed by hepatocellular carcinoma (n = 4, 8%). The median OS was not reached, and the PFS for all immunotherapies was 4.9 months. The median OS period and PFS for non-small cell lung cancer (NSCLC) patients were 13 and 4.9 months, respectively, which were similar to those in many clinical trials. For NSCLC patients, the OS and PFS were only 0.63 and 1.37 months for squamous cell type NSCLC, and for patients who were PD-L1 negative, the OS and PFS were only 11.53 and 2.6 months, respectively. The most common adverse events in this study included fatigue (42%), rashes (22%), nausea (20%), and fever (20%), while one patient developed severe deep venous thrombosis and tissue inflammation, which was not confirmed in previous clinical trials. CONCLUSIONS:The histological subtype, the intensity of the PD-L1 expression, and the timing of treatment affected the NSCLC therapeutic results. It is recommended that clinical tests be conducted in order to enhance therapeutic effectiveness. It is expected that more testing, observation-based studies, and research results will validate their efficacy and the tolerance levels of patients.

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Safety and Efficacy of Immune Checkpoint Inhibitors in Patients on Dialysis: A Retrospective Case Series.

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