Defining High-Risk Disease Biology in Multiple Myeloma: A Narrative Review

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Multiple myeloma (MM) is a heterogeneous, incurable blood cancer.
• Variability in treatment response necessitates precise risk stratification.
• Identifying high-risk MM is critical for guiding therapy and predicting prognosis.

Purpose of the Study:

• To review biological determinants of high-risk MM.
• To explore implications for treatment intensification and novel agent selection.
• To discuss stratified clinical trial enrollment based on risk.

Main Methods:

• Critical examination of current literature on MM biological drivers.
• Analysis of molecular, genomic, and proliferative markers.
• Review of extramedullary dissemination and measurable residual disease (MRD) dynamics.

Main Results:

• High-risk MM is characterized by specific genomic abnormalities (e.g., del(17p), TP53 mutation), increased proliferation, and extramedullary disease.
• The 2024 IMS/IMWG framework integrates genomic markers and clinical factors for refined classification.
• Dynamic risk stratification using MRD offers real-time prognostic updates.

Conclusions:

• Biological factors significantly impact MM prognosis and treatment response.
• Precision medicine approaches integrating molecular profiling and AI are essential for individualized MM therapy.
• Future strategies focus on comprehensive profiling for tailored treatment decisions.