Clinical characteristics, management and outcomes in immune checkpoint inhibitor-induced central nervous system demyelinating disease

During Immune Checkpoint Inhibitor Therapy: Epidemiology, Clinical

Triple-M syndrome after immune checkpoint inhibitors: a systematic review of cases-early recognition is critical to survival.

Introduction Immune checkpoint inhibitors have markedly improved outcomes in advanced malignancies by enhancing antitumor immunity, but they may also disrupt immune tolerance and induce immune-related adverse events involving multiple organs; among these, the overlap of myositis, myocarditis, and Myasthenia Gravis (triple-M syndrome) represents a rare but potentially fatal condition with limited evidence guiding its management. Methods We performed a systematic review of case reports and case series published until July 2025 to describe the clinical characteristics, diagnostic findings, treatments, and outcomes of patients developing triple-M syndrome after immune checkpoint inhibitor therapy. Results The syndrome typically occurred early after treatment initiation and presented with rapidly progressive and heterogeneous features, including ocular and bulbar symptoms, muscle involvement, and cardiac manifestations; diagnosis was often challenging due to low sensitivity of routine tests, variable antibody positivity, and limited feasibility of advanced investigations, making clinical suspicion crucial. High-dose corticosteroids were the most frequently used first-line treatment, often combined with intravenous immunoglobulins or plasma exchange, although steroid monotherapy was associated with clinical worsening in some cases; emerging therapies, including targeted monoclonal antibodies and next-generation immunomodulatory agents, have the potential to provide more rapid and effective disease control. Overall prognosis remains poor, with high rates of respiratory failure, severe complications, and oncologic progression following treatment discontinuation. Triple-M syndrome is a severe and under-recognized complication requiring early diagnosis and prompt multidisciplinary management, and further studies are needed to improve diagnostic strategies and optimize treatment while preserving oncologic benefit.

Immune-mediated liver injury caused by checkpoint inhibitors: A case series and review of the literature.

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 agents, exhibit notable efficacy across various types of cancer. Nevertheless, they can trigger immune-related adverse events, among which immune-mediated liver injury (ILICI) occurs in 5-10% of patients. Corticosteroids are currently recommended for management of ILICI; however, the timing, presentation and response to treatment may vary widely. The present study retrospectively reviewed five male patients (median age, 69 years) with various malignancies receiving ICIs who developed ILICI. All patients were treated with anti-PD-1 therapy, and two additionally received anti-CTLA-4 therapy. No patients had a history of liver disease, autoimmune disorders or notable alcohol use, and no relevant drug allergies or toxic exposures were reported. Four patients developed grade 3-4 hepatotoxicity. The median time to onset was 15.5 months (range: 1-30 months), illustrating the delayed and unpredictable nature of ILICI. All patients underwent comprehensive evaluation to exclude other causes of liver injury. In selected cases, liver biopsy revealed features consistent with autoimmune-like hepatitis, aiding in diagnosis and assessment of severity. All patients received systemic glucocorticoids, with resolution of liver injury in most cases. One patient required additional immunosuppressive therapy due to steroid-refractory disease. Notably, liver function tests normalized in three patients following treatment, whereas two patients died from ILICI. The present case series highlights the variable onset and presentation of ILICI, which may occur shortly or long after initiation of ICIs. Timely recognition and prompt treatment are integral components of clinical care. In addition, liver biopsy, while not routinely recommended, can provide valuable diagnostic information in complex cases. The current study provides detailed clinical documentation and biopsy information; however, its interpretation is influenced by the small sample size and retrospective nature of the study. The findings support existing guidelines,and underscore the need for enhanced clinical awareness and standardized management protocols.

Immune checkpoint inhibitors-related cytokine storm syndrome: a systematic review of characteristics, treatment, and outcomes

Objective To analyze and summarize the general patterns and key points of treatment for cytokine release syndrome (CRS) induced by immune checkpoint inhibitors (ICIs), and provide references for the differential diagnosis and treatment of this immune-related adverse event (irAE) and the safe application of ICIs. Methods Case reports published in domestic and international databases were collected. Basic information of patients and CRS were extracted from the included cases to clarify the characteristics and intervention measures of this irAE. Results A total of 58 articles involving 59 patients were finally included, comprising 36 males and 23 females. The average age of the included patients was (58.54 ± 15.29) years, and lung cancer was the most common primary disease. Ten types of ICIs were used during treatment, and CRS occurred within the first four cycles of ICI administration in the vast majority of patients. Abnormal biochemical and inflammatory indicators could contribute to the diagnosis and confirmation of CRS, while the initial clinical manifestations of included patients were mostly non-specific, with about half of them experiencing at least one other concurrent irAE. With active treatment, 50 patients had a good outcome, but 9 patients died. Conclusion CRS induced by ICIs is a rare but severe irAE. Risk factor assessment and patient education should be conducted before initiating ICIs therapy. If symptoms such as fever and hypotension occur during treatment, accompanied by abnormalities in characteristic indicators like C-reactive protein and related cytokines, individualized treatment should be implemented as early as possible to ensure the safe administration of ICIs.

Systemic Sclerosis Induced by Immune Checkpoint Inhibitors from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO): A Case Series

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, improving outcomes in multiple advanced malignancies. Their use is often limited by immune-related adverse events (irAEs), including rare rheumatic irAEs, such as ICI-induced systemic sclerosis (ICI-SSc). Compared to idiopathic SSc, ICI-SSc typically presents with fewer extra-cutaneous manifestations and negative serologies, but data remains limited.[1] This case series describes the clinical presentation, management, and outcomes of patients with ICI-SSc to guide clinicians in balancing autoimmune toxicities with cancer control. A retrospective chart review was conducted on 7 adults diagnosed with systemic sclerosis following ICI exposure between March 2021 and August 2025. All patients were referred to a Canadian academic rheumatology clinic specializing in Immuno-Oncology during ICI therapy. Clinical data was abstracted from medical records, including patient demographics, malignancy type and stage, ICI type and duration, clinical features, serologies, treatment, and outcomes. Of the 7 patients identified, 5 (71.4%) were female and 2 (28.6%) were male, with a mean age (SD) of 63 (10.9) years. Malignancies included: metastatic melanoma (n=4), metastatic squamous cell carcinoma (n=1), breast cancer Stage IIA/IIB (n=1), and metastatic endometrial adenocarcinoma (n=1). ICIs used included: pembrolizumab (n=2), nivolumab (n=1), cemiplimab (n=1), and ipilimumab/nivolumab combination followed by nivolumab monotherapy (n=2), which were discontinued due to SSc symptoms within 1-13 months of initiation. Serologies showed ANA positivity in 4 patients (57.1%), with SSc-specific antibodies (anti-Scl-70) detected in 1 patient. Other antibodies detected included anti-RP-11, anti-RP-155, anti-Ro-52, anti-chromatin, and anti-OJ. 2 patients had negative serologies, 1 with elevated inflammatory markers. All patients had scleordactyl (diffuse 57.1%, limited 42.9%) and extra-cutaneous features, most commonly Raynaud’s phenomenon (71.4%). Other manifestations included inflammatory arthritis (42.9%), nailfold capillary changes (42.9%), esophageal dysmotility (28.6%), telangiectasia (14.3%), and sicca symptoms (14.3%). No patients developed interstitial lung disease, pulmonary arterial hypertension, or scleroderma renal crisis. Management included ICI cessation for all patients, prednisone (85.7%), disease-modifying antirheumatic drugs (mycophenolate mofetil 57.1%, methotrexate 28.6%, hydroxychloroquine 28.6%), infliximab and intravenous immunoglobulins, and vasodilatory therapies. All malignancies were stable at 6 months post-ICI therapy. ICI-SSc is a significant irAE primarily characterized by cutaneous manifestations but, in contrast to previous reports, this case series demonstrates that extra-cutaneous manifestations and seropositivity can occur. Along with ICI-cessation, immunosuppressive therapy was effective in symptom control without compromising cancer stability. This work may assist those involved in caring of patients with ICI-SSc to initiate immunosuppressive therapy and minimize the risk of end-organ complications. [1.] Cho LK. Rheum Dis Clin North Am 2024;50:301-12.

Immune Checkpoint Inhibitors in Cancer Patients with Pre-existing Autoimmune Disease: Comparative Safety and Efficacy in a Registered Systematic Review.

BACKGROUND This study aimed to compare the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with and without pre-existing autoimmune disease (AID). METHODS We conducted a registered systematic review with a restricted meta-analysis. PubMed, EMBASE, and the Cochrane Library were searched for publications from January 2015 through December 2025; a PubMed rerun and source-verification update were completed in May 2026. The prespecified outcomes included any-grade immune-related adverse events (irAEs), grade ≥3 irAEs, autoimmune disease flares, treatment discontinuation, and efficacy outcomes. Comparative studies reporting outcomes for patients with and without pre-existing AID were included. Directly poolable patient-level event data were analyzed separately from adjusted-only, organ-specific, phenotype-specific, treatment-line, and AID-only evidence. RESULTS A total of 25 studies were included, five contributed to the any-grade irAE meta-analysis and four to the grade ≥3 irAE analysis. Pre-existing AID was associated with a higher risk of any-grade irAEs (risk ratio [RR] 1.34, 95% confidence interval [CI] 1.13-1.60), whereas the evidence for grade ≥3 irAEs remained inconclusive (RR 0.99, 95% CI 0.66-1.47). Available data were insufficient to determine whether pre-existing AID modified antitumour efficacy. CONCLUSION Pre-existing AID was associated with an increased risk of any-grade irAEs, whereas comparative evidence for severe toxicity and efficacy remained uncertain. Treatment with ICIs should be individualized instead of withheld solely because of stable pre-existing AID.