The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of many oncological diseases, and their use continues to increase. ICIs are monoclonal antibodies that target immune checkpoints such as PD-1 (programmed cell death protein 1, as seen in nivolumab, pembrolizumab, and cemiplimab), PD-L1 (programmed cell death protein 1 ligand, as seen in atezolizumab, avelumab, and durvalumab), CTLA-4 (cytotoxic T-lymphocyte antigen 4, as seen in ipilimumab and tremelimumab), or LAG-3 (lymphocyte-activating gene 3, as seen in relatlimab), which play a crucial role in immune tolerance to cancer cells.
However, the surge in ICI prescriptions has been accompanied by the occurrence of numerous side effects, some of which are severe or even fatal. ICIs have a different toxicity spectrum than conventional chemotherapy, and most toxicities result from excessive immunity against different organs.
This immune-mediated toxicity can affect various organ systems, including the heart and blood vessels. Pharmacovigilance data from clinical trials conducted by Bristol-Myers Squibb, which marketed ipilimumab (anti-CTLA-4) and nivolumab (anti-PD1), revealed 18 cases (0.09%) of myocarditis among 20,594 subjects.
While cardiac complications induced by immune checkpoint inhibitors (ICIs), particularly autoimmune myocarditis, are widely described, the impact of these treatments on the vascular system remains poorly understood. However, a variety of vascular complications have been reported, ranging from vasculitis of large, medium, and small vessels to a possible increase in arterial thrombotic events, ischemic strokes, and acute coronary syndromes.
The incidence of vasculitis appears to be between 1% and 2% of patients treated with immune checkpoint inhibitors (ICIs). This is emerging as a significant signal in various pharmacovigilance studies, suggesting the involvement of immune checkpoint derepression in the pathophysiology of vasculitis. A translational study demonstrated the major role of CTLA-4 in the pathophysiology of giant cell arteritis (GCA), although the precise mechanisms involved remain to be determined. Therefore, a specific immune environment could promote the development of vasculitis, a phenomenon reproduced by ICI administration.
The increase in arterial thrombotic vascular events was primarily observed in a matched cohort study, which showed a threefold increased risk of arterial thrombotic vascular events following the initiation of ICI therapy. These thrombotic events would coincide with the acceleration of atherosclerosis in patients treated with ICIs. This "accelerated" atherosclerosis could be linked to inflammatory changes within the plaques, causing plaque destabilization or rupture. It is also unreasonable to rule out the possibility that the accelerated atherosclerosis is related to the development of vasculitis in these patients.
Patient treated with an ICI (nivolumab, pembrolizumab, atezolizumab, ipilimumab, cemiplima, or any novel antibody directed against PD-1, PD-L1, CTLA-4, or LAG-3) as monotherapy or in combination with another ICI or with radiotherapy,
Patient over 18 years of age,
WHO performance status: 0 to 2,
Oral informed consent,
History of ICI treatment,
History of chemotherapy or targeted therapy within the last 4 weeks,
Stage 4 PAD,
Severe Raynaud's syndrome,
patients treated with an Immune Checkpoint Inhibitor (ICI) as monotherapy (curative or as an adjunct to surgery) or a combination of ICIs in the dermatology oncology department
Cohort
Prospective
Evaluation of the vascular impact of ICIs (Immune Checkpoint Inhibitors)
Other interventionA multidisciplinary clinical-biological approach to research involving the clinical pharmacology department for the creation of the popmeter (population pharmacokinetic/pharmacodynamic analysis tool), the CIC-CRB1404 for the management of biological samples, the dermatology oncology department (Dr. Raphael Janela) for the recruitment and monitoring of volunteers, and the Inserm U1096 EnVI laboratory for the measurement of lymphocyte and monocyte activation markers.
Determine if there is an increase in aortic arterial stiffness 6 to 8 weeks after the start of ICI treatment.
Evaluation of the variation in pulse wave velocity (PWV) measured by photoplethysmography (Popmeter®, Axelife) between the initial value and the value after 6 to 8 weeks of ICI treatment.
Determine if there is an increase in aortic arterial stiffness one year after the start of ICI treatment
Evaluation of the change in PVO measured by photoplethysmography (Popmeter®, Axelife) between the initial value and the value after 1 year of ICI treatment
Determine if there are, 6 to 8 weeks after the start of ICI treatment: An alteration in systemic hemodynamics and cardiocirculatory coupling,
Evaluation of brachial arterial pressures by photoplethysmography (Popmeter)
Determine if there are one year after the start of ICI treatment: An alteration in systemic hemodynamics and cardiocirculatory coupling,
Evaluation of brachial arterial pressures by photoplethysmography (Popmeter)
Determine if there are, 6 to 8 weeks after the start of ICI treatment: An alteration in systemic hemodynamics and cardiocirculatory coupling,
Evaluation of aortic pressures by photoplethysmography (Popmeter)
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
