Central nervous system (CNS) multiple myeloma

Authored by Open Medicine, published on 2026-04-29 17:42:24.0

CNS myeloma (CNS-MM) is when cancerous plasma cells infiltrate the central nervous system, which is normally protected by the blood–brain barrier. Ben Derman, MD Assistant Professor at University of Chicago offers his guidance on this rare and difficult to manage disease. Originally posted on X.

  1. Symptoms
    Confusion, headache, visual symptoms, weakness, cranial nerve palsies
    • Workup — Essential
      • Brain and spine MRI with gadolinium contrast • Lumbar puncture with flow cytometry, cytopathology, cell count, protein, and infectious disease testing
      • Workup — Certain circumstances
        • Biopsy of affected tissue if above is negative and suspicion is high
        • Definitive diagnosis
          • Clonal plasma cells observed in CSF by immunophenotyping • Tissue diagnosis of clonal plasma cell myeloma in affected CNS tissue
          • Management — Initial therapy / Multimodality therapy
            • Novel agent with prior nonrefractory exposure and CNS penetration: IMiDs (pomalidomide, lenalidomide, thalidomide), venetoclax for t(11;14) ± • Intrathecal methotrexate/cytarabine ± steroid • Intrathecal thiotepa/steroid • Radiation therapy • Evaluation for BCMA CAR T-cell therapy if not previously received • Palliative care consultation
        • Possible diagnosis
          • Leptomeningeal enhancement or parenchymal lesions on MRI without definitive clonal plasma cells demonstrated
          • Management — Initial therapy / Multimodality therapy
            • Novel agent with prior nonrefractory exposure and CNS penetration: IMiDs (pomalidomide, lenalidomide, thalidomide), venetoclax for t(11;14) ± • Intrathecal methotrexate/cytarabine ± steroid • Intrathecal thiotepa/steroid • Radiation therapy • Evaluation for BCMA CAR T-cell therapy if not previously received • Palliative care consultation
tosprivacyDiagnosis and Management of Multiple Myeloma With Central Nervous System InvolvementOutcome of Patients With Central Nervous System Multiple Myeloma (CNS-MM) Treated With CNS-Directed Radiation TherapySecondary CNS myeloma with remission after systemic CNS-penetrating agentsCentral nervous system myeloma: Pathogenesis, diagnosticchallenges, and practical management strategiesMultiple myeloma with central nervous system relapse