Incidence and Distinct Features of Immune Checkpoint Inhibitor-Related Myositis From Idiopathic Inflammatory Myositis: A Single-Center Experience With Systematic Literature Review and Meta-Analysis.

Immune checkpoint inhibitor (ICI)-related myositis is a rare, potentially fatal condition that warrants further studies. Its incidence, clinical features, and prognosis remain poorly understood. To address these gaps, we conducted a systematic review and meta-analysis to evaluate the risk of myositis associated with ICI for solid tumors by analyzing phase III randomized controlled trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). To complement this analysis with clinical data, we evaluated published ICI case reports along with cases from our institutional registry. This registry comprised 422 patients treated with ICIs alone or in combination from September 2014 to June 2021. The analysis revealed an incidence of ICI-related myositis in 6,838 patients in 18 randomized controlled trials of 0.38% (odds ratio 1.96; 95% confidence interval 1.02-3.75) for patients receiving ICIs compared with controls. Detailed analysis of 88 cases from the literature search and our registry showed that myositis induced by PD-1 inhibitors was more frequent than that induced by anti-CTLA-4 agents, revealing a clinically diverse trend including myasthenia gravis and myocarditis. Importantly, having ptosis at the time of onset was significantly associated with the development of concomitant myocarditis (odds ratio 3.81; 95% CI 1.48-9.83), which is associated with poor prognosis. Regarding treatment, most patients received glucocorticoids, and some received immunosuppressants. Our study revealed the incidence of ICI-mediated myositis and the clinical features of myocarditis, highlighting the need for recognition and early intervention.

Hamada N ，Maeda A ，Takase-Minegishi K ，Kirino Y ，Sugiyama Y ，Namkoong H ，Horita N ，Yoshimi R ，Nakajima H ，YCU irAE Working Group ... -  《Frontiers in Immunology》

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors.

To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes. We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available. A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection. ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.

Aldrich J ，Pundole X ，Tummala S ，Palaskas N ，Andersen CR ，Shoukier M ，Abdel-Wahab N ，Deswal A ，Suarez-Almazor ME ... -  《-》

Immune checkpoint inhibitor-associated myasthenia gravis, myositis, and myocarditis overlap syndrome.

Case reports of immune checkpoint inhibitor (ICI) overlap syndrome of myasthenia gravis, myositis and myocarditis, are increasing in the published literature. This is a potentially fatal adverse event of ICIs and emergency physicians need to be familiar with this triad when patients present to the emergency department (ED). We performed a retrospective chart review of the electronic medical record between September 1, 2016 to March 9, 2020. We identified patients with the overlap syndrome who presented to our ED. Seven patients were identified. Most were female and treated with a programmed cell death-1 inhibitor. Most patients presented with abnormal vital signs and the most common symptoms were ptosis, diplopia, dyspnea and fatigue. Most required supplemental oxygen and had a prolonged length of stay. All received steroids in addition to other immunomodulators. Two patients died. Presence of one of the diagnosis should lead to evaluation for the others. Suspicion should be raised by patients presenting with ptosis, muscular weakness, fatigue and dyspnea. Early recognition of this triad can allow for early administration of high-dose glucocorticoids (1-2 mg/kg of prednisone or equivalent), which is the mainstay of treatment. However, it is likely that patients will need further immunomodulators and therefore, will need hospitalization. Emergency physicians should be aware of this potentially lethal triad in cancer patients receiving ICIs. The life-saving interventions in the ED include recognizing the triad, airway support, administration of high-dose glucocorticoids, and early involvement of a multidisciplinary team.

Lipe DN ，Galvis-Carvajal E ，Rajha E ，Wechsler AH ，Gaeta S ... -  《-》

[Clinical features of immune checkpoint inhibitor-related myositis in patients with urological cancer].

Ying YC ，Tang Q ，Yang KW ，Mi Y ，Fan Y ，Yu W ，Song Y ，He ZS ，Zhou LQ ，Li XS ... -  《-》

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life, and safety. While most immune-related adverse events (irAEs) are mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we carried out a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs. We collected retrospective data from patients treated in six Italian centers with ICIs (programmed cell death protein 1 or programmed death-ligand 1 and/or cytotoxic T-lymphocyte antigen 4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, we carried out a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor. This analysis includes cases from Italian institutions (n = 18) and the case reports identified in our systematic literature search (n = 120), for a total of 138 patients. Among these patients, 50 (36.2%) had complete resolution of their neuromuscular/cardiac irAEs, in 21 (15.2%) cases there was a clinical improvement with mild sequelae, and 53 (38.4%) patients died as a result of the irAEs. Factors significantly associated with worse outcomes were early irAE onset, within the first two cycles of ICI (Fisher P < 0.0001), clinical manifestation of both myositis and myocarditis when compared with patients who developed only myositis or myocarditis (chi-square P = 0.0045), and the development of arrhythmia (Fisher P = 0.0070). To the best of our knowledge, this is the largest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, as well as occurrence of arrhythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.

Boutros A ，Bottini A ，Rossi G ，Tanda ET ，Spagnolo F ，Barletta G ，Croce E ，Fava P ，Parisi A ，De Rosa F ，Palla M ，Marconcini R ，Ferrari M ，Grandis M ，Spallarossa P ，Sarocchi M ，Arboscello E ，Del Mastro L ，Lambertini M ，Pronzato P ，Genova C ... -  《ESMO Open》