Multiple Myeloma

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Last updated: April 22, 2026Bookmark

Multiple myeloma is characterised by the accumulation of plasma cells in the bone marrow, the presence of M-proteins in serum and urine, and CRAB (hypercalcaemia, renal dysfunction, anaemia, and bone disease) in symptomatic patients.

Multiple myeloma accounts for 1% of all cancers and 10% of hematologic malignancies. 99% of cases occur over 40 years.

Definition of terms

TermDefinition
Smouldering multiple myelomaAn asymptomatic condition characterised by monoclonal gammopathy with no end-organ or tissue damage. Some patients may progress to MGUS and multiple myeloma.

MGUS vs smouldering myeloma vs multiple myeloma

MGUSSmouldering myelomaMultiple myeloma
M spike (SPEP)YesYesYes
“CRAB” signsNoNoYes
Plasma cells on bone marrow biopsyLess than 10%10% or more> 10%

Revised International Staging System (RISS) for MM

StageDescription
Stage IB2-microglobulin <3.5mg/L AND albumin is 3.5g/dL or greater AND standard genetic AND normal LDH levels
Stage IINot stage I or Stage III (in between)
Stage IIIB2-microglobulin >5.4mg/L AND high-risk cytogenetics

Diagnostic criteria

  1. End-organ symptoms or Labs characteristic of multiple myeloma (CRAB)

AND

  1. Monoclonal protein spike on UPEP or SPEP

AND

  1. Greater than 10% plasma cells on BM biopsy
  • Risk factors
    • African
    • Male
    • Family History of multiple myeloma
  • Signs and Symptoms
    • Bone pain (70%) and pathologic fractures due to lytic lesions
    • Neuropathy due to spinal cord compression
    • Symptoms of anaemia
    • Recurrent and severe infections due to defective antibodies and neutropenia
    • Easy bruising and bleeding due to thrombocytopenia, and interference with coagulation factors and platelet function
    • Symptoms of hypercalcaemia
    • Macroglossia, carpal tunnel syndrome, subcutaneous nodules, and diarrhea due to amyloidosis in 5%
    • Hyperviscosity syndrome (2%)
  • Investigations
    • Peripheral Blood Film
      • Abnormal plasma cells (15%)
      • Rouleaux formation (due to increased plasma proteins. Need 10 RBCs in a row)
    • Bone Marrow Aspirate or Biopsy
      • Increased plasma cells with abnormal forms (>10%)
    • Immunohistochemistry or Flow cytometry
      • CD38+, CD138+, CD45-
    • Serum protein electrophoresis (SPEP)
      • M-spike in the gamma region – IgG (60%), IgA (20%), Light chains (Kappa or lambda),
      • Immune paresis (reduced normal Ig amount)
    • Urine protein electrophoresis (UPEP): 24-hour urine collection for Bence Jones proteinuria (2/3)
    • Hyperalcaemia
    • Elevated Creatinine (20%)
    • Low albumin (advanced disease)
    • Radiograph and CT-scan for areas with bone pain and fractures +/- a general skeletal survey:
      • Lytic bone lesions (’soap bubble appearance”),
      • Pathological fractures,
      • Vertebral body compression,
      • Osteopenia,
      • Osteoporosis
    • ELevated ESR
    • B-2 microglobulin for prognosis
      • <3.5 mg = good prognosis
      • 5.5 mg = poor prognosis
    • FISH
      • Hyperdiploidy (>50% of tumours)
    • ESR: >100
  • Treatment
    • Bone marrow transplant for eligible patients (< 65 years without comorbidities)
      • Primary induction with bortezomib, cyclophosphamide, and dexamethasone
      • Autologous bone marrow transplant
      • Maintenance therapy with lenalidomide
    • Chemotherapy for patients who are ineligible for bone marrow transplant
      • Melphalan, prednisone, and thalidomide
    • Correct hypercalcaemia
    • Ensure proper hydration
    • Prophylactic vaccination
    • Erythropoietin for anemia if there is renal failure
    • Surgery
      • Fixation of pathologic fractures
      • Prophylactic fixation of impending fractures
      • Kyphoplasty for symptomatic vertebral compression fractures
Reference Intervals ›
Biochemistry
ACTHP: <80 ng/L
ALTP: 5–35 U/L
AlbuminP: 35–50 g/L
AldosteroneP: 100–500 pmol/L
Alk. phosphataseP: 30–130 U/L
α-AmylaseP: 0–180 IU/dL
α-FetoproteinS: <10 kU/L
Angiotensin IIP: 5–35 pmol/L
ADHP: 0.9–4.6 pmol/L
ASTP: 5–35 U/L
BicarbonateP: 24–30 mmol/L
BilirubinP: 3–17 μmol/L
BNPP: <50 ng/L
CRPP: <10 mg/L
CalcitoninP: <0.1 mcg/L
Calcium (ionized)P: 1.0–1.25 mmol/L
Calcium (total)P: 2.12–2.60 mmol/L
ChlorideP: 95–105 mmol/L
CholesterolP: <5.0 mmol/L
VLDLP: 0.128–0.645 mmol/L
LDLP: <2.0 mmol/L
HDLP: 0.9–1.93 mmol/L
Cortisol AMP: 450–700 nmol/L
Cortisol MidnightP: 80–280 nmol/L
CK ♂P: 25–195 U/L
CK ♀P: 25–170 U/L
CreatinineP: 70–100 μmol/L
FerritinP: 12–200 mcg/L
FolateS: 2.1 mcg/L
FSHP: 2–8 U/L ♂; >25 menopause
GGT ♂P: 11–51 U/L
GGT ♀P: 7–33 U/L
Glucose (fasting)P: 3.5–5.5 mmol/L
Growth hormoneP: <20 mu/L
HbA1C (DCCT)B: 4–6%
HbA1C (IFCC)B: 20–42 mmol/mol
Iron ♂S: 14–31 μmol/L
Iron ♀S: 11–30 μmol/L
Lactate (venous)P: 0.6–2.4 mmol/L
Lactate (arterial)P: 0.6–1.8 mmol/L
LDHP: 70–250 U/L
LHP: 3–16 U/L
MagnesiumP: 0.75–1.05 mmol/L
OsmolalityP: 278–305 mosmol/kg
PTHP: 0.8–8.5 pmol/L
PotassiumP: 3.5–5.3 mmol/L
Prolactin ♂P: <450 U/L
Prolactin ♀P: <600 U/L
PSAP: 0–4 mcg/mL
Protein (total)P: 60–80 g/L
Red cell folateB: 0.36–1.44 μmol/L
Renin (erect)P: 2.8–4.5 pmol/mL/h
Renin (recumbent)P: 1.1–2.7 pmol/mL/h
SodiumP: 135–145 mmol/L
TBGP: 7–17 mg/L
TSHP: 0.5–4.2 mU/L
T4P: 70–140 nmol/L
Free T4P: 9–22 pmol/L
TIBCS: 54–75 μmol/L
TriglyceridesP: 0.50–2.3 mmol/L
T3P: 1.2–3.0 nmol/L
Troponin TP: <0.1 mcg/L
Urate ♂P: 210–480 μmol/L
Urate ♀P: 150–390 μmol/L
UreaP: 2.5–6.7 mmol/L
Vitamin B12S: 0.13–0.68 nmol/L
Vitamin DS: 50 nmol/L
Arterial Blood Gases
pH7.35–7.45
PaCO₂4.7–6.0 kPa
PaO₂>10.6 kPa
Base excess±2 mmol/L
Urine
Cortisol (free)<280 nmol/24h
Hydroxyindole acetic acid16–73 μmol/24h
Hydroxymethylmandelic acid16–48 μmol/24h
Metanephrines0.03–0.69 μmol/mmol cr.
Osmolality350–1000 mosmol/kg
17-Oxogenic steroids ♂28–30 μmol/24h
17-Oxogenic steroids ♀21–66 μmol/24h
17-Oxosteroids ♂17–76 μmol/24h
17-Oxosteroids ♀14–59 μmol/24h
Phosphate (inorganic)15–50 mmol/24h
Potassium14–120 mmol/24h
Protein<150 mg/24h
Protein/creatinine ratio<3 mg/mmol
Sodium100–250 mmol/24h
Haematology
WCC4.0–11.0 ×10⁹/L
RBC ♂4.5–6.5 ×10¹²/L
RBC ♀3.9–5.6 ×10¹²/L
Hb ♂130–180 g/L
Hb ♀115–160 g/L
PCV ♂0.4–0.54 L/L
PCV ♀0.37–0.47 L/L
MCV76–96 fL
MCH27–32 pg
MCHC300–360 g/L
RDW11.6–14.6%
Neutrophils2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes1.0–4.5 ×10⁹/L (20–45%)
Eosinophils0.04–0.44 ×10⁹/L (1–6%)
Basophils0–0.10 ×10⁹/L (0–1%)
Monocytes0.2–0.8 ×10⁹/L (2–10%)
Platelets150–400 ×10⁹/L
Reticulocytes0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time10–14 s
APTT35–45 s
Paediatric
Pulse Rate (bpm)
Neonate140–160
Infant <1yr120–140
1–5 years110–130
5–12 years80–120
>12 years70–100
Respiratory Rate (tachypnoea)
0–2 months≥60/min
2–12 months≥50/min
1–5 years≥40/min
>5 years≥30/min
Blood Pressure (mmHg)
Term65/45
1 year75/50
4 years85/60
8 years95/65
10 years100/70
Weight Formulas
3–12 months(a + 9)/2 kg
1–6 years2a + 8 kg
>6 years(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn13–20
1 month11–18
2 months10–15
1–2 years10–13
>2 years11–14
MUAC (6 months–5 years)
Obese>17.5 cm
Normal13.5–17.4 cm
At risk12.5–13.4 cm
Moderate malnutrition11.5–12.4 cm
Severe malnutrition<11.5 cm
Developmental Milestones
Social smile1.5 months
Head control4 months
Sits unsupported7 months
Crawls10 months
Stands unsupported10–12 months
Walks12–13 months
Talks18 months
CSF WBC (/mm³)
Term newborn0–25
>2 weeks0–5
Calculator ›

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