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usmle step 2 ck

Multiple Myeloma

Plasma cell malignancy causing monoclonal protein, lytic bone lesions, anemia, renal dysfunction, hypercalcemia, and recurrent infections

Review date
reviewed 2026-05-04
Reading time
9 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Hematology & Oncologycommonlong-term-condition
On this page
Condition details
Hematology & Oncology
common
9 min read
reviewed 2026-05-04
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About This Page

This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.

Key points

  • Multiple myeloma is a malignant plasma cell disorder with monoclonal protein production
  • Classic end-organ damage: CRAB = hyperCalcemia, Renal dysfunction, Anemia, Bone lesions
  • SPEP/UPEP with immunofixation plus serum free light chains evaluate monoclonal protein
  • Lytic bone lesions are punched-out and do not show osteoblastic repair; alkaline phosphatase may be normal
  • Treatment commonly uses proteasome inhibitor, immunomodulatory drug, dexamethasone, and anti-CD38 antibody, with transplant consideration

Overview

Multiple myeloma is clonal proliferation of plasma cells in bone marrow causing monoclonal immunoglobulin or light chain production, osteoclast activation, immune suppression, and organ damage. It exists on a spectrum from MGUS to smoldering myeloma to symptomatic myeloma.

Epidemiology

Myeloma is more common in older adults, men, and Black patients. MGUS is a common precursor state in older adults and progresses to myeloma at about 1% per year. Risk factors include age, family history, obesity, and prior radiation or certain exposures.

Clinical Features

Symptoms
Back pain, rib pain, or pathologic fractures from lytic lesions
Fatigue, dyspnea from anemia
Polyuria, constipation, confusion from hypercalcemia
Recurrent bacterial infections from impaired humoral immunity
Foamy urine, edema, or renal failure symptoms
Neurologic deficits from spinal cord compression
Signs
Bone tenderness, vertebral compression signs
Pallor
Dehydration or altered mental status with severe hypercalcemia
Peripheral neuropathy can occur from disease or therapy

Investigations

First-line
CBC, CMP, calcium, creatinineAnemia, renal dysfunction, hypercalcemia; total protein may be elevated
SPEP/UPEP with immunofixationDetects and characterizes monoclonal protein
Serum free light chain assayImportant for light-chain myeloma and risk stratification
Second-line
Skeletal imagingLow-dose whole-body CT, PET/CT, or MRI detects lytic lesions; plain skeletal survey is less sensitive
Quantitative immunoglobulins and beta-2 microglobulinAssess immune paresis and prognosis
Urinalysis and urine protein studiesLight chain cast nephropathy may have dipstick-negative protein because dipsticks detect albumin preferentially
Specialist
Bone marrow biopsyClonal plasma cells and cytogenetic risk stratification
FISH/cytogeneticsdel(17p), t(4;14), t(14;16), gain 1q are high-risk features

Management

NCCN Guidelines for Multiple Myeloma; ASCO supportive care guidance
1
Initial stabilization
  • Treat hypercalcemia with IV fluids, calcitonin for rapid temporary effect, and bisphosphonate or denosumab
  • Renal dysfunction: hydrate, avoid nephrotoxins, treat light-chain burden urgently
  • Spinal cord compression: urgent MRI, corticosteroids, radiation/surgery evaluation
  • Pain control and fracture stabilization when needed
2
Disease-directed therapy
  • Common induction uses bortezomib, lenalidomide, dexamethasone plus anti-CD38 antibody in many modern regimens
  • Assess eligibility for autologous stem cell transplant
  • Maintenance therapy often includes lenalidomide depending on risk and tolerability
3
Supportive care
  • Bone-modifying agents for myeloma bone disease with dental evaluation to reduce osteonecrosis risk
  • Antiviral prophylaxis with proteasome inhibitors to prevent zoster
  • Vaccination and infection prevention
  • Thromboprophylaxis when using immunomodulatory drugs depending on risk

Complications

  • Renal failure: Light-chain cast nephropathy, hypercalcemia, dehydration, amyloidosis
  • Pathologic fractures and cord compression: Lytic vertebral disease
  • Infections: Pneumonia and encapsulated organisms due to immune paresis
  • Amyloidosis: Restrictive cardiomyopathy, nephrotic syndrome, neuropathy
USMLE Step 2 CK Exam Tips
  • 1CRAB = hyperCalcemia, Renal failure, Anemia, Bone lesions
  • 2Back pain + anemia + renal failure + high protein gap = multiple myeloma
  • 3Punched-out lytic lesions are classic; bone scan can be falsely negative because lesions are purely lytic
  • 4Urine dipstick may miss light chains; order UPEP or free light chains
  • 5Monoclonal spike on SPEP = M protein
  • 6MGUS has M protein without CRAB end-organ damage
  • 7Renal failure in myeloma often comes from light-chain cast nephropathy

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Verified Sources & References

NCCN Clinical Practice Guidelines in Oncology
ASCO Guidelines
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