Hematology Oncology · Year 2 · from Hematology Oncology

Case 1: Multiple Myeloma with CRAB Features

Patient Presentation

Demographics: 68-year-old male

Chief Complaint: Back pain and fatigue for 3 months

History of Present Illness: The patient has had progressive lower back pain for 3 months that does not improve with rest. He also reports significant fatigue, decreased appetite, and constipation. He was recently found to have elevated creatinine on routine labs. He denies fever, weight loss, or night sweats.

Past Medical History:

  • Hypertension
  • Type 2 diabetes mellitus

Physical Examination:

  • Blood pressure: 132/78 mmHg
  • Heart rate: 84 bpm
  • General: Pale, appears fatigued
  • Spine: Tenderness to palpation at L2-L4
  • No hepatosplenomegaly
  • No lymphadenopathy
  • No focal neurological deficits

Workup and Results

Laboratory Studies:

  • Hemoglobin: 9.2 g/dL
  • Creatinine: 2.4 mg/dL (baseline 1.0)
  • Calcium: 12.8 mg/dL (elevated)
  • Albumin: 3.2 g/dL
  • Total protein: 10.4 g/dL (elevated)
  • Beta-2 microglobulin: 6.8 mg/L (elevated)
  • LDH: 245 U/L (upper normal)

Serum Protein Electrophoresis (SPEP):

  • M-spike: 4.2 g/dL (IgG kappa)

Serum Free Light Chains:

  • Kappa: 285 mg/L (elevated)
  • Lambda: 12 mg/L
  • Ratio: 23.75 (abnormal)

Skeletal Survey:

  • Multiple lytic "punched-out" lesions in skull, spine, and pelvis
  • L3 compression fracture

Bone Marrow Biopsy:

  • 65% clonal plasma cells
  • CD138+, cytoplasmic kappa light chain restricted
  • Cytogenetics: Standard risk

Clinical Image

Skull X-ray demonstrating multiple "punched-out" lytic lesions characteristic of multiple myeloma. Bone scans are often negative because there is no osteoblastic activity.

Diagnosis

Multiple Myeloma - IgG Kappa, ISS Stage III

CRAB criteria present:

  • Calcium elevation (12.8 mg/dL)
  • Renal insufficiency (creatinine 2.4 mg/dL)
  • Anemia (hemoglobin 9.2 g/dL)
  • Bone lesions (lytic lesions with compression fracture)

R-ISS Staging: Stage III (beta-2 microglobulin >5.5 mg/L)

Discussion

This case illustrates classic multiple myeloma:

  • CRAB Criteria: The lecture describes the CRAB criteria for myeloma-related organ damage: hypercalcemia, renal insufficiency, anemia, and bone lesions. Any of these in the presence of clonal plasma cells indicates symptomatic myeloma.
  • M-Protein Detection: The lecture explains that SPEP is the primary screening test for M-protein. The tall, narrow spike in the gamma region indicates monoclonal protein production.
  • Lytic Bone Lesions: The lecture notes that myeloma bone lesions are characteristically lytic "punched-out" lesions because plasma cells secrete factors that activate osteoclasts while suppressing osteoblasts. This is why bone scans are often negative.
  • Cast Nephropathy: Renal failure in myeloma is often due to light chains binding to Tamm-Horsfall protein, forming obstructing tubular casts.

Treatment Plan

  1. Pre-treatment Evaluation:
  • Echocardiogram (baseline for cardiotoxic agents)
  • Consider fertility preservation discussion
  1. Induction Therapy:
  • VRd regimen: Bortezomib (proteasome inhibitor) + Lenalidomide (IMiD) + Dexamethasone
  • Consider adding daratumumab (anti-CD38) in high-risk patients
  • 4-6 cycles
  1. Supportive Care:
  • Bisphosphonates (zoledronic acid) for bone disease
  • IV fluids and bisphosphonates for hypercalcemia
  • VTE prophylaxis (IMiDs increase thrombosis risk)
  • Pain management
  1. Transplant Evaluation:
  • Autologous stem cell transplant candidacy assessment
  • High-dose melphalan conditioning
  1. Maintenance:
  • Lenalidomide maintenance post-transplant

Teaching Points

  1. CRAB criteria define symptomatic myeloma requiring treatment
  2. M-protein detected on SPEP; immunofixation confirms type
  3. Bone lesions are lytic (no osteoblastic activity) - bone scans are often negative
  4. VRd (bortezomib-lenalidomide-dexamethasone) is standard induction
  5. Autologous transplant improves survival in eligible patients

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