Skouri, Hadi

ABSTRACT The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant precursor of multiple myeloma (MM). MGUS has been suggested to be associated with a higher risk of cardiovascular diseases, including AFIB, but it is still unclear whether this association is real. Studies are lacking on the impact of atrial fibrillation on health outcomes in this population. The association of AFIB in this population is lagging and merits further investigation. Methods: The study conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) for 2018, including adult patients with primary diagnoses of MGUS and AFIB. Patients were divided into two groups based on AFIB presence. Outcomes assessed included complications, length of stay, mortality, hospital charges, and discharge disposition. Results: The study included 9007 patients with MGUS of whom 2404 had AFIB. Patients with both MGUS and AFIB had higher rates of acute kidney injury [AKI] (31.5% vs. 27.5%; p = 0.002) and pericarditis (2% vs. 1.2%; p = 0.029). They also had longer hospital stays (5 vs. 4 days; p < 0.001) and higher hospitalization costs ($43,729 vs. $41,169; p < 0.001). Conclusions: The study showed that the prevalence of AFIB in MGUS patients is high. Patients with AFIB had increased rates of complications (AKI and pericarditis) and higher mortality compared to patients without AFIB. Further studies screening for AFIB in this patient population are warranted.

Abstract This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.