Background/Objectives: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. Whilst early-onset immune-related toxicities have been well characterized, late-onset toxicities, often emerging in patients with long-term disease control, remain understudied and are frequently overlooked. Methods: To address this knowledge gap, we conducted a retrospective multicentre study in three UK tertiary referral centres, exploring immune-related adverse events in 246 patients with melanoma who received immune checkpoint inhibitors in the advanced setting. We defined late-onset immune-related adverse events as those occurring at least 3 months after the last cycle of immune checkpoint inhibitors. Results: Although most patients experienced early-onset toxicity, almost 15% of patients developed late-onset immune-related adverse events, including skin rash, colitis, hepatitis, and arthritis, among others. These were often challenging to manage and necessitated the use of systemic steroids. Up to 2% of patients presented ultra-late-onset toxicities, defined as those events occurring at least 12 months after treatment completion. Conclusions: This study provides valuable insights into the characteristics of late-onset immune-related adverse events. To further advance our understanding of these late-onset toxicities, dedicated prospective studies are needed to assess risk factors associated with their development and their impact on quality of life. Additionally, translational research focused on finding predictive biomarkers is essential to identify patients at a higher risk of developing delayed adverse events and to understand how best to manage them.

Over the last decade, immune checkpoint inhibitors (ICIs) have dramatically improved the systemic treatment of multiple solid tumour types. However, they can also induce inflammation in an extensive range of normal tissues types. The entity of ICI-induced cholangitis is rare and has not been widely described. We present three cases of ICI-induced cholangitis which illustrate the difficulties associated with its diagnosis and management. We also present associated radiological findings that include intrahepatic duct abnormalities consistent with sclerosing cholangitis-progressive worsening of intrahepatic duct dilatation and pericholecystic haziness suggesting inflammation characteristic of this rare, but severe, toxicity.

Background: Differentiating between immune checkpoint inhibitor (ICI) myocarditis and non-ICI myocarditis is clinically important. Cardiovascular magnetic resonance (CMR) is a well-established method for diagnosing acute myocarditis. The value of CMR for distinguishing ICI myocarditis from non-ICI myocarditis remains unclear, which this study sought to determine. Methods: A total of 54 patients (n = 26 ICI myocarditis; n = 28 non-ICI myocarditis) underwent clinical CMR for the assessment of cardiac function (cines), myocardial fibrosis (native T1-mapping, extracellular volume [ECV] fraction, late gadolinium enhancement [LGE]) and myocardial oedema (native T2-mapping). Results: ICI myocarditis patients were older than non-ICI myocarditis patients (75 years [71–78] vs. 39 years [30–64]; p < 0.001). Both groups had similar left ventricular (LV) ejection fraction (58 ± 11% vs. 58 ± 6%; p = 0.970). ICI myocarditis and non-ICI myocarditis patients also had similar native myocardial T1 values (1041 ± 84 ms vs. 1063 ± 60 ms; p = 0.281), native myocardial T2 values (59 ± 6 ms vs. 59 ± 6 ms; p = 0.943) and ECV (0.32 ± 0.07 vs. 0.31 ± 0.04; p = 0.403). Native myocardial T1 values (Rho = −0.553) and ECV (Rho = −0.502) were significantly associated with LVEF in non-ICI myocarditis patients (both p < 0.05). There was no significant association between myocardial T1 values, T2 values or ECV, with LVEF, in ICI myocarditis patients (all p < 0.05). Non-ICI myocarditis patients had a greater frequency of LGE in the LV compared to ICI myocarditis patients (89% vs. 52% p = 0.005). However, the pattern of LGE was similar between the two patient groups (mostly subepicardial and/or mid-wall). Conclusions: In this single centre retrospective cohort, the findings suggest that quantitative parametric mapping methods by CMR may not differentiate between ICI vs. non-ICI myocarditis. Further work is needed to assess the value of CMR for diagnosing standalone ICI myocarditis.

Immune checkpoint inhibitors (ICI) frequently trigger ICI-colitis, commonly leading to ICI discontinuation. With expanding ICI use, ICI-colitis is emerging as a significant clinical challenge. Cytomegalovirus (CMV) infection is known to occur in ICI-colitis, but its prevalence, risk factors and clinical impact are poorly defined. This study aimed to characterise the clinical trajectory of ICI-colitis patients with concurrent colonic CMV infection as compared to a CMV-negative colitis group. We retrospectively analysed consecutive ICI-treated patients with endoscopically and/or histologically confirmed ICI-colitis at two UK hospitals between 2015 and 2024. Clinical, endoscopic (Mayo Endoscopic Score, MES), treatment and oncologic outcome data were collected. CMV was identified by immunohistochemistry (IHC) on colonic biopsies. CMV-positive colitis cases were compared with CMV-negative colitis using chi- squared, Mann-Whitney U, and multivariable regression analyses. Among 249 ICI-colitis patients, IHC proven CMV-positive colitis was detected in 21 (8.4%). CMV-positive colitis was associated with dual ICI therapy (OR 2.8, CI 1.06-7.15), prior infliximab exposure (OR 6.4, CI 2.56-16.7), bloody stool (OR 2.7, CI 1.05-6.69), and higher endoscopic severity (MES 2-3; OR 4.1, CI 1.60-10.38), despite similar CTCAE diarrhoea grades between groups. They also had a higher likelihood of requiring escalation to advanced therapy (80% vs 41.5%; OR 5.6, CI 1.96-15.74), with this association remaining significant after adjusting for endoscopic severity (p = 0.049). Colectomy rates were higher albeit low overall. Antiviral therapy did not significantly affect corticosteroid duration or recurrence, and CMV tissue status did not influence overall or progression-free survival. Concurrent CMV-positive colitis occurs in a notable subset of ICI-colitis patients and may worsen disease severity, highlighting the importance of endoscopic biopsy, especially in steroid-refractory cases.

Immune checkpoint inhibitors (ICI) use can lead to an array of immune-related adverse events (irAE). Nephritis is considered to be...