Proteasome Inhibitor-Associated PRES in Multiple Myeloma: Pharmacovigilance Evidence of Risk Signals and Concomitant Drug Interactions

Proteasome inhibitors (PIs), essential for multiple myeloma (MM) therapy, are associated with posterior reversible encephalopathy syndrome (PRES), a rare but serious neurotoxic event. Using the FDA Adverse Event Reporting System (2004–2025), we conducted a disproportionality analysis with Bayesian Confidence Propagation Neural Network to assess PI-associated PRES risk and the impact of concomitant medications. Among 315 cases, bortezomib (73.3%) and carfilzomib (24.1%) were predominant, mainly affecting females (72.3%), median age 62, with a median onset of 21 days. Significant risk signals were detected for PIs overall (IC 2.71, 95% CI 2.52–2.84), driven by bortezomib (IC 3.00, 95% CI 2.78–3.16) and carfilzomib (IC 2.96, 95% CI 2.60–3.22). In stratified analyses of concomitant antihypertensives, ACEIs increased risk (IC 2.81, 95% CI 1.94–3.42), while ARBs (IC 1.90, 95% CI 0.34–2.89) and CCBs (IC 2.24, 95% CI 1.47–2.77) suggested risk reduction. Concomitant glucocorticoids significantly lowered risk for bortezomib (IC 0.67, 95% CI 0.41–0.86) and carfilzomib (IC 1.07, 95% CI 0.67–1.36). All PRES cases were serious; carfilzomib had a 53.9% rate of death or life-threatening outcomes. These findings underscore the need for early clinical vigilance during PI therapy and suggest glucocorticoids mitigate PRES risk, warranting further validation.