Abstract
BACKGROUND: Chemotherapy tolerance significantly affects treatment efficacy and survival in multiple myeloma (MM), especially among frail patients. The International Myeloma Working Group Geriatric Assessment (IMWG GA) is widely used for frailty assessment, but limitations remain. Dynamic and integrated assessment approaches may improve risk stratification and support personalized treatment. METHODS: We retrospectively analyzed 111 newly diagnosed MM patients treated at the Third Affiliated Hospital of Sun Yat-sen University (Jan 2018-Jun 2024). IMWG GA and Hematopoietic Score (HS) were assessed at baseline and follow-up. Static and dynamic frailty assessments were compared. Chemotherapy-related adverse events (AEs) were graded per CTCAE 5.0. RESULTS: Chemotherapy tolerance and frailty status changed across cycles. Static assessments showed limited predictive value, while dynamic evaluation with IMWG GA and HS improved risk stratification. IMWG GA differentiated Fit vs. Frail patients for total AEs (HR = 1.81, p = 0.001) and non-hematological AEs (HR = 1.90, p = 0.002); HS strongly stratified hematological AEs (HR=9.91, p < 0.001). Combining both tools, the Hemo-IMWG GA model achieved superior predictive performance for total toxicity (AUC 0.619-0.646; C-index 0.615) and non-hematological toxicity (AUC 0.600-0.618; C-index 0.605), and improved stratification of hematological toxicity (C-index 0.687 vs. 0.600 for IMWG GA, though slightly below HS alone, C-index 0.717). CONCLUSION: Hemo-IMWG GA offers a dynamic, integrated approach for evaluating chemotherapy tolerance in MM. By combining functional and hematopoietic dimensions, it improves prediction of treatment-related toxicity-especially hematological AEs-and aids personalized treatment decisions.