PM&R News   •   August 2021

Anatomy

• Blood: Immunoglobulin-producing Plasma cells (derived from B cells; a lymphocyte sub-type)

Pathophysiology

• Plasma cells: neoplastic proliferation → monoclonal immunoglobulin
  • Proliferation in the bone marrow = skeletal destruction

Epidemiology

• U.S.: 1 – 2% of all cancers
  • > 17% of hematologic malignancies
  • Annual: 4-5/100,000
• Worldwide: 160,000 cases
• 106,000 deaths/year
• Risk factors:
  • Ethnicity:
    • African Americans 2-3x > Caucasians
    • Lowest risk: Asians from Japan, Mexicans
  • Increased incidence: Males > females (1.4:1), ↑ BMI, older age (avg: 66 y/o), 1^st degree relative (3.7x), variation of the 3p22.1 or 7p15.3 genetic loci

Presentation/ Clinical Manifestations

• Anemia: 73% at diagnosis; 97% at some time during disease course
  • fatigue/pallor
• Bone pain: 60%
  • Greatest at the back/chest secondary to movement (none at night); vertebral collapse, rib Plasmacytomas (tumor in ST or skeleton)
• Renal insufficiency: ~50%
  • Increased serum creatinine concentration
    • 2 main causes:  light chain cast nephropathy (aka: myeloma kidney) and hypercalcemia
• Hypercalcemia: 13%
• Cord compression: 5%
  • secondary to vertebral fx or extramedullary plasmacytoma
  • s/s: back pain with weakness and paresthesias; B/B disfunction or incontinence.

The following percents: a retrospective analysis of 1027 sequential patients diagnosed with MM at a single institution:

• Anemia – 73%
• Bone pain – 58%
• Elevated creatinine – 48%
• Fatigue/generalized weakness – 32%
• Hypercalcemia – 28%
• Weight loss – 24%, (50% lost ≥9 kg/19.84 lbs)
• < 5%: paresthesias (5%), hepatomegaly (4%), splenomegaly (1%), lymphadenopathy (1%), and fever (0.7%).
• Acute renal failure or nephrotic syndrome (rare)

Diagnosis

• Imaging (preferred: cross-sectional due to increased sensitivity): lytic lesions present on bone (MRI can detect lesions not yet lytic)
• SPEP (protein electrophoresis of the serum) or UPEP (urine protein electrophoresis) combined with immunofixation (serum or urine): presence of a monoclonal protein (97%)
• total serum protein concentration: increased — typically normal in those with light-chain myeloma (detection via: serum FLC (free light chain), UPEP and urine immunofixation)
• Bone marrow bx: clonal plasma cells >/=10% (96% pts; average typically around 50%)
  • If >60%, 80% progress to end-organ damage in 2 years
• Hypercalcemia: >11 mg/dL (>2.75 mmol/liter).
• Histopathology specimen: (+) plasmacytoma
• Immunophenotype: express CD56 (~70%)
• Free light chain assay: abnormal (90%)

• Definitive dx:

  Clonal bone marrow plasma cells ≥10 percent or bony or soft tissue plasmacytoma (demonstrated via biopsy) + one of the following:

  • (CRAB: calcium level, renal insufficiency, anemia, and bone lesions)

“Presence of a biomarker associated with near inevitable progression to end-organ damage”

Treatment

• autologous hematopoietic cell transplantation (HCT): prolong event-free & overall survival
• Chemo:
  • HCT eligible: triplet regimen, 3-4 mos
  • Non-eligible: triplet regimen, 8-12 cycles; maintenance therapy until progression
    • Frail: doublet therapy until progression
  • Both require maintenance therapies

Patient Education

• No cure: Tx aimed at alleviating symptoms, inducing remission, extending life.
• Increased risk of infection secondary to:
  • Hypoventilation
  • Decreased lymphocytes, plasma cell suppression, and hypogammaglobulinemia

References:

• https://www.uptodate.com/contents/multiple-myeloma-clinical-features-laboratory-manifestations-and-diagnosis?search=multiple%20myeloma&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
• https://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics?search=multiple%20myeloma&topicRef=6643&source=see_link