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Multiple Myeloma (MM)

Multiple Myeloma (MM) is a malignant plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow, resulting in monoclonal (M) protein production, bone destruction, anemia, renal impairment, and immunodeficiency

Also called

Plasma Cell Myeloma

ICD-10

C90.0

Specialty

Hematology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

Multiple Myeloma (MM) is a plasma cell malignancy in which abnormal plasma cells accumulate in the bone marrow and produce a monoclonal immunoglobulin (M protein). This causes bone pain, osteolytic lesions, hypercalcemia, anemia, renal dysfunction, and recurrent infections. Diagnosis is based on bone marrow plasma cells, detection of monoclonal protein, and evidence of end-organ damage (CRAB criteria).

Etiology & Risk Factors

-Etiology

Multiple Myeloma (MM) develops from malignant transformation of plasma cells and is usually preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) or Smoldering Multiple Myeloma (SMM).

Risk Factors

  • Increasing age (>60 years)

  • Male sex

  • African ancestry

  • Family history

  • MGUS

  • Smoldering Multiple Myeloma

  • Obesity

  • Exposure to ionizing radiation

  • Certain occupational chemical exposures

Pathophysiology

Malignant plasma cell proliferation within the bone marrow → excessive production of monoclonal immunoglobulin (M protein) or free light chains → suppression of normal hematopoiesis causing anemia → osteoclast activation leading to osteolytic bone lesions and hypercalcemia → light-chain deposition causing renal injury → reduced normal immunoglobulin production resulting in recurrent infections.

Clinical Presentation

Symptoms

  • Bone pain (especially back or ribs)

  • Fatigue

  • Weakness

  • Weight loss

  • Recurrent infections

  • Polyuria

  • Constipation

  • Nausea

  • Confusion (hypercalcemia)

  • Paresthesia

Signs

  • Pallor

  • Bone tenderness

  • Pathological fractures

  • Kyphosis

  • Dehydration

  • Neurological deficits (spinal cord compression)

  • Signs of renal impairment

History Taking

-Ask about:

  • Bone pain
  • Fatigue
  • Recurrent infections
  • Weight loss
  • Fractures
  • Back pain
  • Symptoms of hypercalcemia
  • Renal symptoms
  • Neurological symptoms
  • Previous MGUS
  • Family history

Physical Examination

General Examination

Look for:

  • Pallor

  • Weight loss

  • Dehydration

Musculoskeletal Examination

Assess for:

  • Bone tenderness

  • Vertebral tenderness

  • Pathological fractures

  • Reduced mobility

Neurological Examination

Look for:

  • Peripheral neuropathy

  • Spinal cord compression

  • Muscle weakness

Investigations

-Complete Blood Count (CBC)

Typical findings:

  • Normocytic normochromic anemia

  • Leukopenia (advanced disease)

  • Thrombocytopenia (advanced disease)

-Blood Tests

  • Serum calcium (elevated)

  • Creatinine and renal function

  • LDH

  • Albumin

  • Beta-2 microglobulin (prognostic marker)

-Serum Protein Electrophoresis (SPEP)

  • Detects M protein (monoclonal paraprotein)

-Serum Immunofixation

  • Identifies the type of monoclonal immunoglobulin

-Serum Free Light Chain Assay

  • Detects kappa and lambda light chains

  • Essential for light-chain myeloma

-Urine Studies

  • Urine protein electrophoresis

  • Bence Jones proteins (free light chains)

-Bone Marrow Aspiration and Biopsy (Gold Standard)

Typical findings:

  • ≥10% clonal plasma cells

  • Plasma cell infiltration

-Imaging

Preferred imaging:

  • Whole-body low-dose CT

  • Whole-body MRI

  • PET-CT (selected patients)

May show:

  • Osteolytic lesions

  • Pathological fractures

  • Vertebral collapse

Diagnosis

Diagnosis is based on:

  • Bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma
  • Monoclonal protein on SPEP/UPEP or free light chain assay
  • Myeloma-defining events:
    • CRAB features
    • SLiM biomarkers (when present)
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Management

-Initial Treatment

Transplant-eligible patients:

  • Induction therapy (e.g., Bortezomib + Lenalidomide + Dexamethasone [VRd])

  • Autologous stem cell transplantation

  • Maintenance therapy (commonly lenalidomide)

Transplant-ineligible patients:

  • Combination chemotherapy with targeted agents

  • Continuous therapy based on fitness

-Supportive Care

  • Bisphosphonates (e.g., zoledronic acid)

  • Adequate hydration

  • Pain control

  • Blood transfusions if needed

  • Treatment of hypercalcemia

  • Infection prevention and vaccination

  • Dialysis if severe renal failure

-Relapsed Disease

  • Proteasome inhibitors

  • Immunomodulatory drugs

  • Monoclonal antibodies (e.g., daratumumab)

  • CAR T-cell therapy or bispecific antibodies in selected patients

Complications

  • Pathological fractures
  • Hypercalcemia
  • Renal failure
  • Recurrent infections
  • Spinal cord compression
  • Hyperviscosity syndrome (rare)
  • Amyloidosis (AL amyloidosis)
  • Disease relapse

Prognosis

The prognosis depends on disease stage, cytogenetic abnormalities, renal function, and treatment response. Modern therapies, including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and autologous stem cell transplantation, have significantly improved survival, although Multiple Myeloma remains an incurable but highly treatable disease

Key Points / Clinical Pearls

  • Multiple Myeloma (MM) is a malignant plasma cell disorder.
  • The classic CRAB features are HyperCalcemia, Renal impairment, Anemia, and Bone lesions.
  • Serum protein electrophoresis (SPEP) detects the monoclonal (M) protein.
  • Bone marrow biopsy shows ≥10% clonal plasma cells.
  • Bence Jones proteins are monoclonal free light chains detected in urine.
  • Whole-body CT or MRI is preferred for detecting bone lesions.
  • Autologous stem cell transplantation is standard for eligible patients.
  • Bisphosphonates reduce skeletal complications.
  • Modern targeted therapies have markedly improved outcomes.
  • Multiple Myeloma is generally treatable but remains incurable in most patients.
  •  
  • National Center for Biotechnology Information (NIH). Multiple Myeloma, StatPearls.
  • Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group Updated Criteria for the Diagnosis of Multiple Myeloma. Lancet Oncol. 2014;15:e538-e548.
  • International Myeloma Foundation (IMF). Multiple Myeloma Diagnostic Criteria.
  • National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma.
  • MedlinePlus, National Library of Medicine (NIH). Multiple Myeloma: Health Topic.