8 - Multiple Myeloma Flashcards
Multiple Myeloma
Neoplastic profileration of a single clone of plasma cells producing a monoclonal immunoglobulin
Multiple Myeloma - Incidence
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
IgM
Makes your blood hella viscous because it needs more space
Multiple Myeloma - Timeline
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.
MGUS
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.
Multiple Myeloma - Clinical Presentation
Anemia - 73% Bone Pain - 58% Elevated Creatinine - 48% Fatigue/Generalized Weakness - 32% Hypercalcemia - 28% Weight Loss - 24%, 1/2 of whom lost ≥ 9 kg
Multiple Myeloma - Diagnosis
Bone Marrow histology (see cancer cells)
Monoclonal immunoglobulins in serum & urine
X-ray, CT (lytic lesions)
Multiple Myeloma - Blood Work
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
Multiple Myeloma - Urine Evaluation
24-hr protein
Protein electrophoresis (quantitative Bence Jones protein)
Immunofixation electrophoresis
Multiple Myeloma - Other Evaluation
Skeletal Survey
Unilateral bone marrow aspirate and biopsy evaluation with immunohistochemistry or flow cytometry, cytogenetics and FISH
Imaging as indicated
Multiple Myeloma - Cytogenetics, Interphase FISH, Flow Cytometry - Poor Prognosis
t(4;14)(p16;q32)
t(14;16)(q32;q23)
-17p13
Multiple Myeloma - Cytogenetics, Interphase FISH, Flow Cytometry - Intermediate Prognosis
-13q14
Multiple Myeloma - Types of paraprotein secretion
Complete Ig
Light chain
Both
Non-secretory
Multiple Myeloma - SPEP & UPEP
Monoclonal protein (M-Spike) Gamma globulin SPIKE!!!
MGUS - Criteria for diagnosis
M Protein
Smoldering Myeloma - Criteria for diagnosis
M Protein ≥ 3 g/dL spike
and/or
Monoclonal plasma cells in bone marrow ≥ 10
No end organ damage
Active Myeloma - Criteria for diagnosis
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)
CRAB features
Calcium elevation (>11.5 mg/L or ULN) Renal dysfunction (Serum creatinine > 2 mg/dL) Anemia (Hb
Risk of patient with MGUS progressing to active Myeloma
1% per year, so it may take over 20 years.
It really depends on M-spike, though.
MGUS - Management
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
Smoldering Myeloma - Management
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)
Multiple Myeloma - Stage I
β2M
Mutliple Myeloma - Stage II
Not Stage I or III
Multiple Myeloma - Stage III
β2M ≥ 5.5 mg/L
Multiple Myeloma - Treatment - Transplant candidate
Induction treatment (nonalkylator-based induction x 4 - 6 cycles)
Stem cell harvest
Stem cell transplantation
Maintenance
Mutliple Myeloma - Treatment - Non-Transplant Candidate
Induction treatment
Maintenance
Multiple Myeloma - Autologous Stem Cell Transplantation
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
Multiple Myeloma - Novel Agents
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
Multiple Myeloma - Thalidomide
Anti-angiogenic effects, combatting the microvessel density in bone marrow associated with disease activity
Multiple Myeloma - Lenalidomide/Pomalidomide
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
Bortezomib
Reversible Proteasome Inhibitor
Prevent the breakdown of protein
Cells drown in their own protein
Multiple Myeloma - Skeletal Complications
~ 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%
Multiple Myeloma - Treatment of Bone Metastases
Chemotherapy Orthopaedic Intervention Kyphoplasty Analgesics Radiotherapy Osteoclast inhibition bisphosphonates/RANKL Inhibitors
Multiple Myeloma - Bisphosphonates
They line the bones and are resorbed by osteoclasts who then DIE because bisphosphonates are POISON!!
Uncommon complication = Avascular necrosis of maxilla or mandible
Multiple Myeloma - Denosumab (off label!!)
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
