Uncovering prognostic biomarkers through a pharmacovigilance study: the case of RDW.

Background: Recent studies highlighted the potential role of Red cell distribution width (RDW) as a prognostic biomarker in oncology. RDW has been associated with systemic inflammation, a key factor in cancer progression. While clinical trials and cohort studies suggest a correlation between RDW alterations and poor prognosis, its specific role in patients undergoing Immune Checkpoint Inhibitor (ICI) therapy remains unclear.

Objective: This study aims to explore the potential relationship between RDW alterations and treatment outcomes in patients treated with PD-1 inhibitors using pharmacovigilance data from Eudra Vigilance (EV).

Methods: We retrieved Individual Case Safety Reports from EV database, reporting pembrolizumab or nivolumab as suspected drug (January 2015 to March 2025). The Reporting Odds Ratio (ROR) with its 95% of Confidence Interval (95% CI) was computed to assess if drugs of interest have a lower/higher probability of reporting adverse events (AEs) belonging to the System Organ Class "Investigation".

Results: Of 12,289 ICSRs, 6981 (56.8%) involved pembrolizumab and 5308 (43.2%) nivolumab. Most ICSRs referred to male patients aged 18-64. Pembrolizumab showed higher reporting probability of "Platelet count decreased" (ROR 2.41, 95% CI 2.14-2.72), "Neutrophil count decreased" (ROR 1.55, 95% CI 1.34-1.80), "White blood cell count decreased" (ROR 1.50, 95% CI 1.26-1.78), "Blood creatinine increased" (ROR 1.19, 95% CI 1.01-1.42), "C-reactive protein increased" (ROR 1.28, 95% CI 1.07-1.53) compared to nivolumab.

Conclusions: This study provides new insights into the potential prognostic value of RDW in patients treated with ICIs. These results warrant further investigations to determine its utility in monitoring ICI therapy.