What is the treatment for central nervous system (CNS) involvement in multiple myeloma, specifically brain myeloma?

Treatment of Central Nervous System (CNS) Involvement in Multiple Myeloma

The treatment of brain myeloma (CNS involvement in multiple myeloma) should include a combination of radiation therapy, intrathecal chemotherapy, and systemic therapy with immunomodulatory drugs to achieve the best possible outcomes. 1, 2

Diagnostic Evaluation

• CNS involvement in multiple myeloma is rare, occurring in approximately 1% of multiple myeloma patients 3
• Evaluation should include:
  • Lumbar puncture with cerebrospinal fluid (CSF) analysis for malignant plasma cells 1
  • Brain and spine MRI to detect leptomeningeal and/or parenchymal involvement 1
  • Assessment for high-risk features (plasma cell leukemia, skull plasmacytomas) which are common in CNS myeloma 1

Treatment Approach

Radiation Therapy

• Cranial irradiation (CI) significantly improves survival compared to patients who do not receive radiation therapy 3, 2
• Craniospinal irradiation is commonly used (48.9% of cases) with a median dose of 20 Gy in 10 fractions 2
• Whole brain radiotherapy (20% of cases) or focal brain/spine radiation are alternative approaches based on disease distribution 2

Intrathecal Chemotherapy

• Multi-dose intrathecal chemotherapy should be administered as part of the treatment regimen 1
• Options include:
  • Standard intrathecal chemotherapy (methotrexate, cytarabine, corticosteroids) 2-3 times per week until clearance of malignant cells, followed by consolidation 4
  • Liposomal cytarabine (50 mg every other week) for approximately 6 cycles may be considered 4

Systemic Therapy

• Immunomodulatory drugs (IMiDs) are a critical component of treatment for CNS myeloma 1, 5
• Recent case reports show promising efficacy of newer agents:
  • Pomalidomide has shown better CNS penetration than earlier IMiDs 6, 5
  • Daratumumab-based regimens have shown responses in recent cases 5
  • Marizomib (a proteasome inhibitor that crosses the blood-brain barrier) shows promise 6, 5
• Standard proteasome inhibitors like bortezomib have limited CNS penetration 6

Treatment Outcomes and Prognosis

• Overall prognosis remains poor with median survival of 2.0-4.6 months from CNS diagnosis 3, 1, 2
• However, long-term survival can be achieved in select patients:
  • Complete response after radiation therapy is associated with improved survival (median 7.3 months) 2
  • Patients with focal brain involvement have better outcomes than those with diffuse disease 2
  • Combination of radiation, multi-dose intrathecal chemotherapy, and IMiD-based therapy can achieve long-term survival (median 17.1 months in responders) 1

Common Pitfalls to Avoid

• Delaying CNS-directed therapy, as CNS myeloma progresses rapidly 3
• Relying on single-modality treatment, as multimodal therapy is associated with better outcomes 1
• Using only systemic agents with poor blood-brain barrier penetration 6
• Inadequate follow-up imaging and CSF analysis to monitor treatment response 2

Monitoring and Follow-up

• Regular neurological assessments to monitor for clinical improvement or deterioration 4
• Follow-up CSF analysis and MRI imaging to assess treatment response 2
• Consider dexamethasone (4 mg three times daily) on days of intrathecal therapy to prevent arachnoiditis 4