A Simulation-Based Assessment of Dosage Regimen Appropriateness for Multiple Myeloma Medicines Reflecting Demographic...

Bridging studies are often waived for orphan diseases such as multiple myeloma (MM) due to challenges in conducting clinical trials in small and heterogeneous populations. However, demographic and regional differences between trial participants and Asian populations may influence drug exposure and response. This study evaluated potential differences in drug exposure and response between multinational clinical trial populations (TP) and the Korean patients (KP). Representative drugs from major MM treatment classes were selected based on the available population pharmacokinetic models. Covariate distributions were compared between TP and KP using clinical trial data and Korean real-world data. Simulations were conducted to assess differences in key exposure metrics. Efficacy and safety were evaluated for drugs showing ≥ 10% differences in exposure. Simulated carfilzomib exposure was approximately 12%-15% lower in KP than in TP across two dosing regimens, corresponding to an estimated 4%-9% lower predicted overall response rate based on the published exposure-response data. Conversely, simulated lenalidomide exposure was approximately 25% higher in KP, corresponding to an approximately 1.27-fold higher estimated probability of grade ≥ 3 hematologic adverse events. No meaningful exposure differences were observed for daratumumab, melphalan, or panobinostat. These findings suggest that demographic and regional differences between TP and KP may translate into measurable differences in predicted drug exposure for selected multiple myeloma therapies. Simulation-based approaches integrating real-world demographic data may help prioritize drugs or indications that warrant further pharmacokinetic evaluation or focused bridging studies in Korean or broader East Asian populations.