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Oncology > 8 - Multiple Myeloma > Flashcards

8 - Multiple Myeloma Flashcards

1
Q

Multiple Myeloma

A

Neoplastic profileration of a single clone of plasma cells producing a monoclonal immunoglobulin

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2
Q

Multiple Myeloma - Incidence

A

Second most common hematologic malignancy
African americans 2 - 3 times higher risk than Caucasians, risk is lower in Asians
Slightly more frequent in men than women
Disease of older adults (median age at diagnosis is 66)
10% of patients younger than 50
2% younger than 40

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3
Q

IgM

A

Makes your blood hella viscous because it needs more space

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4
Q

Multiple Myeloma - Timeline

A 
MGUS (smoldering myeloma)
Active Myeloma
First-line therapy
Plateau remission
Relapse
Second-line therapy
Plateau remission
Relapse
Third-line therapy
Refractory relapse

Each plateau keeps getting higher and higher in terms of M-protein level

Disease not curable.

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5
Q

MGUS

A

Monoclonal Gammopathy of Undetermined Significance
No other signs of Multiple Myeloma
Often discovered accidentally via other blood work
At this point, it’s a pre-stage, so they don’t have cancer yet, but they need lifelong follow-ups to prevent progression to cancer.

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6
Q

Multiple Myeloma - Clinical Presentation

A 
Anemia - 73%
Bone Pain - 58%
Elevated Creatinine - 48%
Fatigue/Generalized Weakness - 32%
Hypercalcemia - 28%
Weight Loss - 24%, 1/2 of whom lost ≥ 9 kg
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7
Q

Multiple Myeloma - Diagnosis

A

Bone Marrow histology (see cancer cells)
Monoclonal immunoglobulins in serum & urine
X-ray, CT (lytic lesions)

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8
Q

Multiple Myeloma - Blood Work

A

CBC w/ differential & platelet counts
BUN, Creatinine
Electrolytes, calcium, albumin, LDH
Serum quantitative immunoglobulins
Serum protein electrophoresis and immunofixation
β2-M
Serum free light chain assay

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9
Q

Multiple Myeloma - Urine Evaluation

A

24-hr protein
Protein electrophoresis (quantitative Bence Jones protein)
Immunofixation electrophoresis

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10
Q

Multiple Myeloma - Other Evaluation

A

Skeletal Survey
Unilateral bone marrow aspirate and biopsy evaluation with immunohistochemistry or flow cytometry, cytogenetics and FISH
Imaging as indicated

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11
Q

Multiple Myeloma - Cytogenetics, Interphase FISH, Flow Cytometry - Poor Prognosis

A

t(4;14)(p16;q32)
t(14;16)(q32;q23)
-17p13

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12
Q

Multiple Myeloma - Cytogenetics, Interphase FISH, Flow Cytometry - Intermediate Prognosis

A

-13q14

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13
Q

Multiple Myeloma - Types of paraprotein secretion

A

Complete Ig
Light chain
Both
Non-secretory

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14
Q

Multiple Myeloma - SPEP & UPEP

A 
Monoclonal protein (M-Spike)
Gamma globulin SPIKE!!!
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15
Q

MGUS - Criteria for diagnosis

A

M Protein

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16
Q

Smoldering Myeloma - Criteria for diagnosis

A

M Protein ≥ 3 g/dL spike
and/or
Monoclonal plasma cells in bone marrow ≥ 10
No end organ damage

17
Q

Active Myeloma - Criteria for diagnosis

A

M protein in serum and/or urine
Monoclonal plasma cells in bone marrow ≥ 10^2
≥ 1 CRAB feature (Calcium elevation, renal dysfunction, anemia, bone disease)

18
Q

CRAB features

A 
Calcium elevation (>11.5 mg/L or ULN)
Renal dysfunction (Serum creatinine > 2 mg/dL)
Anemia (Hb
19
Q

Risk of patient with MGUS progressing to active Myeloma

A

1% per year, so it may take over 20 years.

It really depends on M-spike, though.

20
Q

MGUS - Management

A

No therapy alters the natural history of the disease
Repeat studies in 3 - 6 months
If stable, repeat yearly going forward
If low-risk, less frequent follow up can be considered
Bisphosphonates are NOT indicated

21
Q

Smoldering Myeloma - Management

A

Deferral of chemotherapy until progression to symptomatic disease
Follow closely every 3 - 4 months with SPEP, CBC, Creatinine & serum calcium
Metastatic bone survey considered annually (asymptomatic bone lesions may develop)

22
Q

Multiple Myeloma - Stage I

A

β2M

23
Q

Mutliple Myeloma - Stage II

A

Not Stage I or III

24
Q

Multiple Myeloma - Stage III

A

β2M ≥ 5.5 mg/L

25
Q

Multiple Myeloma - Treatment - Transplant candidate

A

Induction treatment (nonalkylator-based induction x 4 - 6 cycles)
Stem cell harvest
Stem cell transplantation
Maintenance

26
Q

Mutliple Myeloma - Treatment - Non-Transplant Candidate

A

Induction treatment

Maintenance

27
Q

Multiple Myeloma - Autologous Stem Cell Transplantation

A

Mel 200 mg/m^2 = standard conditioning regimen (VERY HIGH DOSES!!!!)
Advanced age and impaired renal function are not contraindications by themselves
Liver, pulmonary & cardiac function are crucial

28
Q

Multiple Myeloma - Novel Agents

A

Treat not only plasma cells but the surrounding stroma, because they are so interdependent

Thalidomide - Imid (immunomodulator)
Lenalidomide - Imid (immunomodulator)
Pomalidomide - Imid (immunomodulator)
Bortezomib - Proteosome antagonist

29
Q

Multiple Myeloma - Thalidomide

A

Anti-angiogenic effects, combatting the microvessel density in bone marrow associated with disease activity

30
Q

Multiple Myeloma - Lenalidomide/Pomalidomide

A

Immunomodulatory derivatives of thalidomide
More potent than thalidomide
Dose-dependent decrease in TNF-α and IL-6
Induces apoptosis, G1 growth arrest
Enhances activity of Dexamethasone
More favorable toxicity profile than thalidomide

31
Q

Bortezomib

A

Reversible Proteasome Inhibitor
Prevent the breakdown of protein
Cells drown in their own protein

32
Q

Multiple Myeloma - Skeletal Complications

A

~ 80% of patients with multiple myeloma have evidence of skeletal involvement on skeletal survey

Increased osteoclast activity
Decreased osteoblast activity

Vertebrae - 65%
Ribs - 45%
Skull - 40%
Shoulders - 40%
Pelvis - 30%
Long bones - 25%
33
Q

Multiple Myeloma - Treatment of Bone Metastases

A 
Chemotherapy
Orthopaedic Intervention
Kyphoplasty
Analgesics
Radiotherapy
Osteoclast inhibition bisphosphonates/RANKL Inhibitors
34
Q

Multiple Myeloma - Bisphosphonates

A

They line the bones and are resorbed by osteoclasts who then DIE because bisphosphonates are POISON!!
Uncommon complication = Avascular necrosis of maxilla or mandible

35
Q

Multiple Myeloma - Denosumab (off label!!)

A

High affinity monoclonal Ab that binds RANKL
SubQ injectoin
does not bind to TNF-α, TNF-β, TRAIL or CD40L
Inhibits formation and activation of osteoclasts

Oncology (23 decks)

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