Introduction: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data. Methods: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria. Results: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70–93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14–96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients. Conclusions: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity.

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, but they may cause a wide range of immune-related adverse events (irAEs). Hepatic toxicity occurs in approximately 1–6% of patients treated with nivolumab and usually presents with a hepatocellular pattern responsive to corticosteroids. The cholestatic-predominant immune-mediated hepatitis seems to respond poorly to immunosuppression. We describe an 87-year-old man with metastatic melanoma treated with nivolumab who developed steroid-refractory, cholestatic-predominant immune-mediated hepatitis after 18 cycles of therapy. Laboratory tests revealed a mixed but predominantly cholestatic pattern (ALT 585 U/L, GGT 2261 U/L, total bilirubin 2.0 mg/dL). Imaging excluded biliary obstruction or hepatic metastases. Liver biopsy showed acute lobular hepatitis with intracanalicular cholestasis and mild bile duct injury, consistent with immune-mediated, drug-induced injury (Ishak score 5). Mycophenolate mofetil produced only partial biochemical improvement. The patient died one month later from influenza A pneumonia in the context of combined immunosuppressive therapy. This case illustrates a cholestatic-predominant phenotype of nivolumab-induced hepatitis, characterized by poor corticosteroid response and incomplete recovery despite second-line immunosuppression. Recognition of this entity is essential, as early introduction of agents such as mycophenolate may improve outcomes. In elderly and frail patients, however, the risks of intensified immunosuppression must be carefully balanced against infection risk, highlighting the need for individualized management and vigilant monitoring.

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced solid tumors but can trigger severe immune-related adverse events (irAEs). Among the rarest and most life-threatening is hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome driven by uncontrolled immune activation. Case Presentation: We report the case of an 80-year-old man with clear cell renal carcinoma with sarcomatoid features who developed secondary hemophagocytic lymphohistiocytosis (HLH) after receiving four cycles of adjuvant pembrolizumab therapy. Following four cycles of immunotherapy, he presented with persistent fever, pancytopenia, hyperferritinemia (>49,000 ng/mL), hypofibrinogenemia, and elevated soluble IL-2 receptor (>7500 U/mL), fulfilling at least five HLH-2004 diagnostic criteria. Despite treatment with high-dose corticosteroids and intravenous anakinra (100 mg every 6 h), his condition rapidly deteriorated, leading to multiorgan failure and death. Discussion: ICI-induced HLH is an exceptional but increasingly recognized irAE, with fewer than 30 pembrolizumab-related cases reported to date. Diagnosis is challenging due to its nonspecific presentation, which can mimic infection, hepatic toxicity, or disease progression. The pathogenesis is believed to involve excessive activation of cytotoxic T cells and cytokine storm. While established pediatric protocols (HLH-94, HLH-2004) guide management, adult cases often require individualized approaches using corticosteroids and cytokine-targeted therapies such as IL-1 or IL-6 blockade. Conclusions: HLH secondary to ICIs should be considered in the differential diagnosis of patients receiving immunotherapy who develop unexplained fever and cytopenia. Early recognition and prompt initiation of immunosuppressive therapy are critical to improving outcomes in this potentially fatal complication.

Sodium-glucose cotransporter-2 (iSGLT2) inhibitors, which include dapagliflozin, canagliflozin and empagliflozin, are a class of drugs initially used in the oral treatment of diabetes, heart failure and renal failure. They target the reabsorption of glucose in the kidney. Although they bring benefit to patients with these conditions and in general produce few adverse effects, in some cases, iSGLT2 can cause serious adverse effects such as metabolic acidosis, and fungal or bacterial urinary infections. Oncology patients, who in general have a weak immune system and are usually treated with chemotherapy and/or immunotherapy, are more susceptible to this type of adverse events than other patients. For this reason, it is necessary to adequately select the patients eligible to receive this type of drug and evaluate the potential benefits for them. In this series of five cases, we present two cases of metabolic acidosis, two cases of bacterial urinary sepsis, and one case of fungal urinary sepsis that occurred in patients admitted to the Medical Oncology Department of the University Hospital of Salamanca in 2023.

Background: Platinum-based therapies for patients with advanced non-small-cell lung cancer (NSCLC) have classically provided overall survival (OS) rates of six to nine months and objective response rates (ORRs) of 20–30%. Whether prior immunotherapy determines a different response to platinum is currently unknown. This study aimed to analyse the current response characteristics to platinum as a second-line treatment for advanced NSCLC (PD-L1 ≥50%) after first-line immunotherapy. Methods: This retrospective study was conducted at the University Hospital of Salamanca (CAUSA) between 2016 and 2023 with patients who had advanced NSCLC (PD-L1 ≥50%) treated with second-line platinum-based therapies after immunotherapy (without mutations in EGFR, ALK or ROS1 and with Eastern Cooperative Oncology Group (ECOG) ≤1 during the first- and second-line treatments). Survival and response correlation analyses (Kaplan-Meier and log rank tests in SPSS v. 25) were performed. Subsequently, the results were compared with historical cohorts (PubMed, COCHRANE, ScienceDirect, Embase, and the clinical trial registry) who had received platinum-based therapies for advanced NSCLC. Results: Seventeen patients were analysed (11 male and 6 female). Their median age was 67 years (interquartile range, 50–77 years). Fifteen patients (88.2%) were smokers or former smokers. The patients’ main histology was adenocarcinoma (9 patients, 52.9%). All first-line treatments applied pembrolizumab (median dose: 12 cycles). Second-line platinum-based therapy achieved OS of 25 months (95% CI: 7–45 months) and progression-free survival (PFS) of 6 months (95% CI: 2.5–95 months). The ORR was 47.1% [seven patients with a partial response (PR) and one patient with a complete response (CR)]. Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed. The one-year survival rate was 58.8%. The historical OS for first-line platinum-based doublets is 7 to 12 months, with PFS of three to five months and an ORR of 17–30%. Conclusions: The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients’ platinum response, though future confirmatory studies are necessary.