Project description:The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis. Because of the high mortality of irMG, measures to increase the vigilance of medical teams are necessary to ensure the timely identification of the signs of irMG and early treatment, particularly in the early course of ICI therapy. The diagnostic plans should be comprehensive and include the evaluation of other organ systems, such as the dermatological, gastrointestinal, respiratory, neuromuscular, and cardiovascular systems, in addition to the traditional diagnostic tests for MG. Treatment plans should be individualized on the basis of the extent of organ involvement and clinical severity. Additional therapeutic studies on irMG in the future are required to minimize irAE-related mortality and increase the safety of patients with cancer in the ICI era.
Project description:Immune checkpoint inhibitors (ICIs) are improving cancer treatments strikingly. The raising use leads to the augmented occurrence of immune related events. Myocarditis is a rare, but severe form of these adverse events. Nine patients with proven ICI induced myocarditis were subjected to myocardial biopsy. The tissue was used for RNA-seq analyses.
Project description:Immune checkpoint inhibitor therapy has been shown to improve outcomes across many types of malignancies. However, immune checkpoint inhibitor has been associated with several immune-related adverse events including myocarditis. We describe the case of a 69-year-old man with fulminant myocarditis likely due to pembrolizumab therapy, complicated by biventricular failure with cardiogenic shock. Because of deterioration in hemodynamic status refractory to conventional immunosuppression, therapeutic plasma exchange was performed, resulting in a rapid reduction of serum pembrolizumab levels, and marked clinical, radiological, and biochemical improvement. To our knowledge, this is the first reported case on the successful use of plasma exchange for pembrolizumab-associated fulminant myocarditis.
Project description:Since the beginning of the COVID-19 pandemic, clinical, radiological, and histopathological studies have provided evidence that organizing pneumonia is a possible consequence of the SARS-CoV2 infection. This post-COVID-19 organizing pneumonia (PCOP) causes persisting dyspnea, impaired pulmonary function, and produces radiological abnormalities for at least 5 weeks after onset of symptoms. While most patients with PCOP recover within a year after acute COVID-19, 5-25% of cases need specialized treatment. However, despite substantial resources allocated worldwide to finding a solution to this problem, there are no approved treatments for PCOP. Oral corticosteroids produce a therapeutic response in a majority of such PCOP patients, but their application is limited by the anticipated high-relapse frequency and the risk of severe adverse effects. Herein, we conduct a systematic comparison of the epidemiology, pathogenesis, and clinical presentation of the organizing pneumonias caused by COVID-19 as well as other viral infections. We also use the clinical efficacy of corticosteroids in other postinfection OPs (PIOPs) to predict the therapeutic response in the treatment of PCOP. Finally, we discuss the potential application of a candidate anti-inflammatory and antifibrotic therapy for the treatment of PCOP based on the analysis of the latest clinical trials data.
Project description:ObjectiveWe sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies.MethodsWe conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response.ResultsSixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response).ConclusionICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.
Project description:Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these syndromes, information about the main imaging findings is limited.MethodsWe conducted a retrospective observational study including all adult patients referred to the Rheumatology Department of a single-center due to ICI-induced arthritis who underwent imaging studies [ultrasound (US), magnetic resonance imaging (MRI), and 18F-FDG PET/CT)] between January 2017 and January 2022.ResultsNineteen patients with ICI-induced arthritis with at least one diagnostic imaging assessment were identified (15 US, 4 MRI, 2 18F-FDG PET/CT). Most patients were male (84.2%), with a median age at inclusion of 73 years. The main underlying diagnoses for ICI treatment were melanoma in five cases. The distribution of ICI-induced arthritis was as follows: PMR-like (5, 26.2%), RA-like (4, 21.1%), PsA-like (4, 21.1%), and others (6, 31.6%). All RA-like patients had US findings indistinguishable from conventional RA patients. In addition, 3/5 (60%) of PMR-like patients had significant involvement of the hands and wrists. Abnormal findings on MRI or PET-CT were reported by clinical symptoms. No erosions or myofascitis were seen.ConclusionsICI-induced arthritis patients present inflammatory patterns on imaging studies similar to conventional inflammatory arthropathies, and therefore these syndromes should be followed carefully and treated according to these findings.
Project description:Oxaliplatin given systemically is associated with pneumonitis in less than 1% of cases. This case report describes acute respiratory failure, due to bronchiolitis organising pneumonia, in a patient with colorectal carcinoma being treated with hyperthermic intraperitoneal chemotherapy which included oxaliplatin and CPT-11 (irinotecan). The clinical course, the lack of an identifiable infectious agent and the complete response to corticosteroids suggested a drug-induced cause. After ruling out CPT-11, oxaliplatin was considered to be the causal agent. The unusual feature of this case was that pneumonitis developed after intraperitoneal administration of oxaliplatin. Oxaliplatin-associated respiratory complications can occur whatever route the drug is administered.