Evaluation des effets secondaires de la chimiothérapie à base d’inhibiteurs de protéasome chez les patients atteints de myélome multiple

Abstract

This dissertation provides a comprehensive, practice oriented review of adverse effects associated with proteasome inhibitor (PI) – based chemotherapy in multiple myeloma (MM). After summarizing MM fundamentals — pathobiology, CRAB/SLiM treatment triggers, complications, and standard care — the work examines the pharmacological profile of bortezomib, carfilzomib, and ixazomib, including their shared mechanism (β5 chymotrypsin like 20S inhibition leading to ER stress and plasma cell apoptosis), key pharmacokinetics, and dosage forms. Clinically, it synthesizes the PI toxicity landscape: peripheral neuropathy (most prominent with bortezomib; modulated by dose, schedule, and subcutaneous route), cytopenias (notably thrombocytopenia), gastrointestinal effects, viral reactivation, renal complications, and carfilzomib related cardiovascular events. The dissertation also appraises quality of life impact (neuropathic pain, fatigue, nutritional and psychosocial burden) and outlines prevention / management strategies structured by standard grading: antiviral prophylaxis, weekly / subcutaneous schedules, dose modifications, early screening and patient education, and systematic hematologic, renal, and cardiovascular monitoring. The practical118 section describes the data collection approach and analysis of PI related adverse events in treated patients, explores risk factors (age, comorbidities, cumulative dose, pre-existing neuropathy), and develops actionable recommendations for clinicians and pharmacists to optimize benefit–risk balance and treatment adherence