Multiple myeloma is a biologically heterogeneous plasma cell malignancy characterized by highly variable clinical presentation, disease course and treatment response. Over the past two decades, the introduction of high-dose chemotherapy with autologous stem cell transplantation and the development of novel agents—including immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies—have substantially improved survival outcomes. Nevertheless, treatment selection remains challenging due to differences in patient fitness, comorbidities, frailty and disease-related risk factors. This narrative review summarizes current evidence on risk-adapted systemic treatment strategies in multiple myeloma, focusing on therapeutic decision-making in newly diagnosed and relapsed/refractory disease. A comprehensive literature search was conducted using major biomedical databases to identify clinically relevant studies, guidelines and meta-analyses published between 2000 and 2024. Emphasis was placed on treatment approaches tailored to transplant eligibility, biological risk profile and patient-related factors. Recent data support the use of combination regimens incorporating proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies as standard therapy across different disease stages. High-dose chemotherapy followed by autologous stem cell transplantation remains the standard of care for eligible patients, while less intensive regimens are recommended for elderly or frail individuals. In relapsed or refractory disease, triplet or quadruplet regimens have demonstrated improved response rates and survival, although cumulative toxicity and treatment resistance remain major concerns. In conclusion, modern management of multiple myeloma requires a personalized, risk-adapted approach that balances treatment efficacy with tolerability and quality of life. Ongoing advances in targeted therapies and risk stratification are expected to further refine treatment algorithms and improve long-term outcomes.
ISSN-online 2360-2473 / ISSN-print 1223-0472
