Redefining central nervous system multiple myeloma: From rare phenomenon to emerging entity

Area of Science:

• Hematology
• Neuro-oncology
• Clinical Research

Background:

• Central nervous system involvement in multiple myeloma (CNS-MM) is a rare, aggressive complication.
• Despite advances in multiple myeloma (MM) treatment, survival for CNS-MM remains poor.
• Early recognition and management of CNS-MM are significant clinical challenges.

Purpose of the Study:

• To review the current literature on CNS-MM epidemiology, risk factors, clinical features, diagnostics, and therapeutics.
• To focus on emerging biomarkers and novel treatments for CNS-MM.
• To hypothesize that CNS-MM is a distinct biologic entity with unique tropism and resistance patterns.

Main Methods:

• Literature review of epidemiology, risk factors, clinical features, diagnostic modalities, and therapeutic approaches for CNS-MM.
• Analysis of emerging biomarkers and new treatment options.
• Synthesis of current data to support a distinct biologic entity hypothesis.

Main Results:

• CNS-MM typically presents in relapsed/refractory disease with high-risk features and a median survival under 6 months.
• Systemic treatments have limited efficacy due to poor blood-brain barrier penetration.
• Novel therapies like CAR-T cells and bispecific antibodies show promise but require more data.

Conclusions:

• CNS-MM may be an underdiagnosed, biologically distinct entity requiring specialized strategies.
• Integrating novel diagnostics (e.g., CSF ctDNA, sBCMA) with CNS-penetrant therapies is key.
• Screening high-risk patients is recommended to improve outcomes.