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Inhibiteurs de point de contrôle immunitaire : schéma double dose ou schéma standard, comédications, quel impact pour les patients ?
Mémoire de Master / Thèse d'exercice   Open Access

Inhibiteurs de point de contrôle immunitaire : schéma double dose ou schéma standard, comédications, quel impact pour les patients ?

Julien Colard-Thomas
Masters , Université de Montpellier
29/03/2023

Résumé

Cancer Inhibiteurs de point de contrôle immunitaire Schéma double dose Toxicité immuno-induite Corticoïdes Antibiothérapie Immunothérapie Inhibiteurs de la pompe à protons
Immune checkpoint inhibitors are immunotherapy treatments that have become the standard of care for an increasing number of solid tumors. Their complex mechanism of action involves the immune system and the gut microbiota. They have generated a new paradigm in patient management, including for the treatment of specific toxicities known as immune-related.New extended-interval dosing strategies based on pharmacokinetic simulations have been widely used during the COVID-19 pandemic to reduce hospital visits. However, few studies have examined the tolerance of these protocols in real-life conditions.We conducted a retrospective study for 686 patients receiving extended and/or standard regimen, as their first immunotherapy treatment, in two Montpellier hospitals between 2019 and 2021. Primary outcome was difference in grade ≥ 3 immune-related adverse events with extended-interval regimen. We found no difference in severe toxicity between the two strategies, yet we evidenced an increase in toxicities of all grades with extended regimen.In addition, several drugs have been thought to reduce the efficacy of checkpoint inhibitors and to affect patient survival, mostly through deleterious effects on the microbiota. We performed a review of the literature on the subject and compiled the main studies and meta-analyses looking for an impact of comedications on the results of immunotherapy. Three families of widely prescribed molecules appear to be the most detrimental: corticosteroids, antibiotics and proton pump inhibitors. All these results suggest the necessity of a global therapeutic strategy for these patients.

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