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Abstract: Background: Cardiovascular (CV) adverse events (AEs), especially atrial fibrillation (AF) and hypertension, have been reported in patients receiving treatments for chronic lymphocytic leukemia (CLL), including Bruton’s tyrosine kinase inhibitors (BTKis). Although these AEs are managed effectively in most cases and AE management guidelines exist, practical management approaches are inconsistent across regions and practices. We aimed to address these inconsistencies by developing consensus recommendations. Summary: A European expert panel was assembled comprising eight hematologists and six cardiologists. Literature analysis, expert interviews, and the Delphi method were used to gain consensus on screening, monitoring, and treatment of AF and hypertension statements. Key Messages: Maintaining BTKi treatment is paramount to maximize time to next treatment; for patients at high risk of progression, this can be achieved by appropriately treating hypertension and AF and adjusting the BTKi dose. Patients should be risk-stratified as low, moderate, high, or very-high risk of cancer therapy-related CV toxicity and treated according to their disease status so that CLL treatment can be maintained. Patient education on symptom monitoring, home blood pressure monitoring, and electrocardiograms (baseline, every 3 months) are recommended to detect/monitor AF and hypertension. Close collaboration between hematologists and cardiologists is vital to achieve optimal patient outcomes.
Keywords: Bruton’s tyrosine kinase inhibitors, chronic lymphocytic leukemia, cardiovascular adverse events, ibrutinib
Published in DiRROS: 01.07.2026; Views: 82; Downloads: 66
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Abstract: Atherosclerosis is a progressive arterial disease characterized by chronic inflammation, with interleukin-27 (IL-27) implicated as both a pro- and anti-inflammatory cytokine. This prospective cohort study evaluated association of circulating IL-27 levels in peripheral artery disease patients undergoing elective endovascular revascularization, with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) over a median follow-up of 311 days. Elevated IL-27 levels were significantly associated with increased risk of MACE and MALE in unadjusted analyses. After adjusting for established cardiovascular and PAD risk factors, IL-27 remained an independent predictor of MACE (HR 2.95; p = 0.039), but not MALE. These findings indicate that elevated IL-27 levels are associated with unfavourable long-term prognosis.
Keywords: peripheral artery disease, interleukin-27, endovascular revascularization, major adverse cardiovascular events, major adverse limb events
Published in DiRROS: 06.03.2026; Views: 354; Downloads: 253
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Abstract: Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy (CAR-T) but has rarely been reported following therapy with immune checkpoint inhibitors (ICI). We present a clinical case of severe CRS after ICI therapy for advanced non-small-cell lung cancer (NSCLC). After the third cycle of ipilimumab and nivolumab the patient presented with fever, hypotension and somnolence, leading to acute respiratory failure, acute kidney and hepatic failure, capillary leak syndrome, requiring ICU (intensive care unit) care. She recovered after receiving tocilizumab and steroid therapy. Subsequently, we found 17 clinical cases of advanced NSCLC patients in peer review, experiencing CRS as an adverse event of treatment with ICI. We review those cases in detail and compare the similarities and outcomes. Conclusion: CRS is a serious, life-threatening complication that is rare after ICI therapy for solid cancers but becoming increasingly frequent since ICI therapies are broadening indications. When presented with clinical symptoms, considering CRS is crucial, as early recognition is key to timely intervention and favorable outcome for the patient.
Keywords: on-small-cell lung cancer, immune checkpoint inhibitors, cytokine release syndrome, immune- related adverse events, case report
Published in DiRROS: 22.08.2025; Views: 737; Downloads: 440
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Keywords: allergies, immunotherapy, allergens, adverse events, registries
Published in DiRROS: 02.07.2025; Views: 830; Downloads: 525
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Abstract: Background. Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy.Patients and methods. A retrospective analysis of patients with metastatic melanoma treated with immuno-therapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups.Results. Among the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE co-hort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.Conclusions. Patients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall re-sponse rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.
Keywords: immune related adverse events, immunotherapy, metastases, melanoma
Published in DiRROS: 22.07.2024; Views: 1240; Downloads: 718
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