Evaluation of emergency department visits and immune-related adverse effects (irAEs) in patients treated with nivolumab.

INTRODUCTION: The development of immune checkpoint inhibitors (ICIs) represents one of the most significant advancements in cancer treatment over the past decade. Nivolumab, a widely used ICI, has been incorporated into the therapeutic regimens for various cancers. As with any drug, this drug also has side effects, including class-specific immune-related adverse effects (irAEs). Although irAEs are not rare, their diagnosis can be challenging. This study examines the emergency department (ED) visits of patients undergoing nivolumab therapy, focusing on diagnostic challenges, evaluating the management, and outcomes of irAEs in the ED setting. MATERIAL AND METHODS: A retrospective cohort study was conducted on adult patients who received nivolumab therapy for any cancer between April 1, 2018, and March 31, 2023, at a large, urban tertiary care center. In this study, we evaluated the ED visits of patients receiving nivolumab. In addition to previous studies, we evaluated irAEs in detail (percentage, recognizability, risk factors, reasons for late recognition, and outcome). Patient data were collected from electronic medical records and patient's medical files. The anamnesis, laboratory, and imaging results, ED management, and consultation notes were examined separately for each ED visit. Logistic regression models were employed to identify significant univariable predictors of ED visits and irAEs. RESULTS: A total of 199 patients were included in the study, all of whom had metastatic cancer. Of these, 154 patients (77.4%) received nivolumab therapy for non-small cell lung cancer. Most patients (71.9%, n = 143) had at least one additional comorbidity. One hundred and eleven patients (55.8%) presented to the ED. Hypertension (OR: 2.425, 95% CI: 1.226-4.795, p = 0.011) and chronic obstructive pulmonary disease (OR: 2.489, 95% CI: 1.133-5.468, p = 0.023) were identified as risk factors for ED visits. A total of 21 irAEs were diagnosed (14 in ED, 6 in the oncology clinic, and 1 in the inpatient ward). Univariate analysis found no significant association between irAE diagnosis and any specific factors. CONCLUSION: A significant proportion of the patients treated with nivolumab for advanced cancer present to ED for ICI-related adverse events, although most cases were not attributable to irAEs. Due to the vague symptomatology of irAEs, their recognition and diagnosis in the ED can be challenging. Close collaboration between ED physicians and oncologists is paramount to the management of patients with cancer in the ED.

Updates and emerging trends in the management of immune-related adverse events associated with immune checkpoint inhibitor therapy.

The rapidly expanding class of therapies targeting immune checkpoints for the treatment of various cancers now includes 8 clinically approved agents: a lymphocyte-activation gene 3 (LAG-3) inhibitor (relatlimab), a cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitor (ipilimumab), three programmed cell death protein 1 (PD-1) inhibitors (nivolumab, pembrolizumab and cemiplimab), and three programmed cell death ligand-1 (PD-L1) inhibitors (atezolizumab, durvalumab, and avelumab). Previously, we reviewed the mechanisms of immune-related adverse events (irAEs), strategies for management of irAEs, and highlighted similarities as well as differences amongst clinical guidelines from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC), and European Society for Medical Oncology (ESMO). Herein, we provide an update that includes discussion of changes to these clinical guidelines since our last review, the new LAG-3 targeted agents, emerging patterns of irAEs, and new directions for improved monitoring and treatment of irAEs that could incorporate interdisciplinary pharmacist-led teams, artificial intelligence, and pharmacogenomics.

Toxicity in the era of immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding of irAEs and develop effective treatment options, there is pressing need for preclinical models recapitulating the clinical settings. In this review, we describe current preclinical models and immune implications of ICI-induced skin toxicities, colitis, neurological and endocrine toxicities, pneumonitis, arthritis, and myocarditis along with their management.

Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system.

BACKGROUND: Immune-related adverse events (irAEs) always occur during treatment with immune checkpoint inhibitors (ICIs). Patients with nervous system cancer (NSC) may gain clinical benefit from ICIs, but irAEs in NSC patients are rarely examined. Therefore, our study systematically summarized reports of irAEs in NSC. METHODS: We obtained information from the FDA adverse event reporting system from the first quarter (Q1) of 2013 to the fourth quarter (Q4) of 2022. We examined use of a combination of ICIs and chemotherapy (ICI_Chemo) or chemotherapy only (ICI_Chemo) for patients with NSC. Multiple disproportionality analyses were applied to assess irAEs. Multiomics data from the gene expression omnibus (GEO) database were analyzed to explore potential molecular mechanisms associated with irAEs in NSC patients. RESULTS: Fourteen irAEs were identified in 8,357 NSC patients after removing duplicates; the top five events were seizure, confused state, encephalopathy, muscular weakness and gait disturbance. Older patients were more likely to develop irAEs than were younger patients. From the start of ICIs_Chemo to irAE occurrence, there was a significant difference in the time to onset of irAEs between age groups. irAEs may occur via mechanisms involving the inflammatory response, secretion of inflammatory mediators, and aberrant activation of pathologic pathways. CONCLUSIONS: This study helps to characterize irAEs in NSC patients treated with ICIs. We combined GEO database analysis to explore the potential molecular mechanisms of irAEs. The results of this study provide a basis for improving the toxic effects of ICIs in NSC patients.

Clinical features, treatment, and outcome of nivolumab induced cholangitis.

Background Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging and treatment of nivolumab induced cholangitis.Methods Case reports, case series and clinical studies of nivolumab induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023.Results Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was 7 cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and 7 patients (18.4%) did not improve.Conclusions Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.

Digital ischemia: a rare immune-related adverse event of immune checkpoint inhibitors-case report and review of the literature.

Immune checkpoint inhibitors (ICIs) play a crucial role in treating various cancers. While ICIs are invaluable in the fight against different cancers, they also pose the risk of immune-related adverse events (irAEs), which can range widely in symptoms and severity. Rheumatologic complications, including digital ischemia, are among the irAEs. While rare, they require early detection for effective management. The aim of the study is to present a case report on digital ischemia related to immunotherapy and to conduct a literature review on relevant cases. We present a case involving a patient from our oncology department who developed, pericarditis, digital ischemia and anti-centromere antibodies during immunotherapy with pembrolizumab for non-small cell lung cancer (NSCLC). We collaborated with our rheumatology department to initiate treatment, including corticosteroids, iloprost, and mycophenolate mofetil. Through the follow-up, the patient showed clinical improvement. A literature review identified only 10 relevant articles, highlighting the rarity of digital ischemia as an irAE. Corticosteroids and vasodilators were commonly used treatments, with amputation unavoidable in 40% of cases. IrAEs are becoming more common due to the widespread use of ICIs. For this reason, it is crucial to diagnose and treat rare IrAEs, such as digital ischemia, as early as possible to improve outcomes.

First Reported Case of Pure Red Cell Aplasia Related to Sotorasib.

We herein report a 64-year-old man with KRASG12C-mutated advanced lung adenocarcinoma previously treated with immune checkpoint inhibitors (ICIs). One month after starting second-line sotorasib treatment, the patient experienced a progressive decline in serum hemoglobin levels. Anemia was accompanied by markedly elevated serum erythropoietin levels and decreased reticulocyte levels. Bone marrow aspiration revealed pure red cell aplasia. No secondary causes other than medication use were identified. Suspected causative drugs were sotorasib and ICIs. Discontinuation of sotorasib for one week improved his anemia; therefore, the causative drug was identified as sotorasib.

From tumor to tolerance: A comprehensive review of immune checkpoint inhibitors and immune-related adverse events.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for various malignancies by harnessing the body's immune system to target cancer cells. However, their widespread use has unveiled a spectrum of immune-related adverse events, highlighting a critical balance between antitumor immunity and autoimmunity. This review article delves into the molecular immunology of ICIs, mapping the journey from their therapeutic action to the unintended induction of immune-related adverse events. We provide a comprehensive overview of all available ICIs, including cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, programmed death-ligand 1 inhibitors, and emerging targets, discussing their mechanisms of action, clinical applications, and the molecular underpinnings of associated immune-related adverse events. Special attention is given to the activation of autoreactive T cells, B cells, cytokine release, and the inflammatory cascade, which together contribute to the development of immune-related adverse events. Through a molecular lens, we explore the clinical manifestations of immune-related adverse events across organ systems, offering insights into diagnosis, management, and strategies to mitigate these adverse effects. The review underscores the importance of understanding the delicate interplay between enhancing antitumor responses and minimizing immune-related adverse events, aiming to guide future research and the development of next-generation ICIs with improved drug safety profiles.

Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients.

OBJECTIVE: Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI). METHODS: A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262). RESULTS: Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4-20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs). CONCLUSION: ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

Misdiagnosis of severe and atypical oxaliplatin­related hypersensitivity reaction following chemotherapy combined with PD­1 inhibitor: A case report and literature review.

Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67-year-old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein-1 (PD-1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL-6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune-related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin-related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD-1 inhibitor was administered. In addition, this apparent severe oxaliplatin-related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.

A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab.

The case was an 80-year-old Japanese man. He was diagnosed with right renal cell carcinoma when he was 74. After laparoscopic radical nephrectomy, the patient received interferon, sorafenib, axitinib, and nivolumab therapy. The patient developed rapid progressive insulin-dependent diabetes mellitus (DM) after 46 courses of nivolumab monotherapy (772 days from the first nivolumab treatment). Glutamic acid decarboxylase antibody, islet cell cytoplasmic antibody, islet cell antigen-2 antibody, insulin antibody, and zinc transporter 8 antibody were all negative. Human leukocyte antigen (HLA) typing showed DRB1*09:01, DRB1 *13:02, DQB1*03:03, and DQB1 *06:04. Multiple daily insulin injections were started. However, controlling his blood glucose by standard multiple daily insulin injection treatments was difficult. The patient survived more than two years after the onset of immune checkpoint inhibitor-associated DM (ICI-DM). This is a valuable report of late-onset ICI-DM with a detailed patient background and clinical course over two years after the first dose of nivolumab.

Construction of a nomogram with IrAE and clinic character to predict the survival of advanced G/GEJ adenocarcinoma patients undergoing anti-PD-1 treatment.

Objective: This study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors. Method: A dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model. Results: After consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model's accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients. Conclusion: This study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

Analysis of Immune-Related Adverse Events of Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma: A Multicentre Cohort Study.

Introduction: Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment. Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022. Patients were categorized into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs. Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: group 1 (n = 84) had no irAEs, group 2 (n = 37) had mild irAEs (grade 1-2), and group 3 (n = 29) had severe irAEs (grade ≥3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to group 1 (9.5 months) and group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both group 1 and group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS. Conclusion: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A + B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.

A Case of Cholangitis as a Nivolumab-Induced Immune-Related Adverse Event in a Patient with Pulmonary Metastasis After Surgery for Oral Cancer.

We report a case of cholangitis, an immune-related adverse event (irAE), caused by the administration of nivolumab in a patient with lung metastasis of oral cancer. A 72-year-old man developed pulmonary metastasis after surgery for oral cancer. Hepatic enzyme abnormalities were observed after the second session of treatment, and irAE cholangitis was diagnosed based on the results of the blood test results and endoscopy findings. We suggested steroid treatment, but the patient refused it. Therefore, he was treated with ursodeoxycholic acid. The cholangitis gradually deteriorated, the patients' general condition worsened, and he died 169 days after the onset of cholangitis.

A Case Report of Pembrolizumab-Induced Allergic Hepatitis.

The immune checkpoint inhibitor pembrolizumab is now considered a first-line treatment for recurrent or metastatic head and neck squamous cell cancer. Pembrolizumab is less toxic than conventional chemotherapy but may result in immune-related adverse events. We report a case in which liver injury occurred just two days after the administration of pembrolizumab plus chemotherapy. A 48-year-old woman achieved a complete response after chemoradiotherapy for cT2N3bM0 squamous cell carcinoma of the oropharynx with multiple lymph node metastases. However, the tumor recurred one year later, and she was started on pembrolizumab plus chemotherapy. On day 3, her alanine aminotransferase and aspartate transaminase concentrations markedly increased. She was initially diagnosed with drug-induced liver injury and all medications were withdrawn. Her liver function recovered within two weeks without intervention. The lymphocyte transformation test was only positive for pembrolizumab. Clinicians should consider pembrolizumab-induced allergic hepatitis as a possible cause of liver injury after excluding liver metastasis and immune-related adverse events.

Immune-related Adverse Event with Checkpoint Inhibitors Might Be an Emerging Underlying Disease of Steroid-related Osteonecrosis of the Femoral Head: A Case Report.

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of advanced metastatic and immunogenic cancers. However, these therapies could cause immune-related adverse events (irAEs), which require high-dose glucocorticoid administration. Case Report: A 52-year-old man with metastatic renal cell carcinoma received ICI therapy. Two weeks later, he suffered from severe irAEs and received glucocorticoid therapy for 13 months. Twenty-one months after the initiation of glucocorticoid administration, he presented to us with bilateral hip pain and was diagnosed with bilateral osteonecrosis of the femoral head (ONFH). Conclusion: IrAEs associated with ICI therapy might be an emerging underlying disease of ONFH.

Use of IV immunoglobulin to treat steroid resistant, immune checkpoint inhibitor-induced pure red cell aplasia: A case report.

Pure red cell aplasia (PRCA) is characterised by normocytic normochromic anaemia, reticulocytopenia and reduced erythroid precursors in bone marrow. PRCA as an immune-related adverse event secondary to immune checkpoint inhibitor (ICI) therapy is rare. Steroids are usually used first line to treat ICI-induced PRCA. Here, we report a case of ICI-induced PRCA with no response to steroids but where intravenous (IV) immunoglobulin was successfully used second line. ICI therapy was reinitiated following PRCA resolution. PRCA recurrence did not occur.

Immune Checkpoint Inhibitor-Related Cerebellar Toxicity: Clinical Features and Comparison with Paraneoplastic Cerebellar Ataxia.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, and the association with immune-related adverse events (irAEs) is well-established. However, cerebellar irAEs are poorly defined and their relationship with paraneoplastic disorders remains unclear. Our aim was (i) to characterize cerebellar irAE; (ii) to compare it with paraneoplastic cerebellar ataxia (PCA). We performed a multicenter, retrospective, cohort study of patients developing new-onset, immune-mediated, isolated/predominant cerebellar dysfunction after ICI administration. In addition, a systematic review following PRISMA guidelines was performed. Cerebellar irAE cases were compared with a consecutive cohort of patients with PCA. Overall, 35 patients were included, of whom 12 were original cases (males: 25/35 (71%), median age: 65 [range: 20-82]). The most frequent tumor was non-small cell lung cancer (12/35, 34%). Anti-PD1 were adopted in 19/35 (54%). Symptoms developed at a median of 11 weeks after ICI onset. Neuronal antibodies were detected in 15/31 patients tested (48%). Cerebrospinal fluid was inflammatory in 25/30 (83%). Magnetic resonance imaging showed cerebellar hyperintensities in 8/35 (23%). Immunotherapy was applied in 33/35 cases (94%), and most patients improved with residual disability (16/35, 46%). When compared with a series of PCA (n = 15), the cerebellar irAE group was significantly more associated with male sex, lung cancer (rather than gynecological/breast cancers), isolated ataxia, and a better outcome. We provide a detailed characterization of cerebellar irAE. Compared to PCA, differences exist in terms of tumor association, clinical features, and outcome. Clinical presentation-antibody-tumor triad in the ICI group only partially reflects the associations described in paraneoplastic disorders.