3.27 WIER Multiple Myeloma

Question 1

Mult Myeloma

Answer 1

Malignancy of late B cels that mature principally into neoplastic plasma cells that generally produce a complete and/or partial (light chain) monoclonal Ig protein

Question 2

Name the four components of CRAB

Answer 2

CRAB:

-HyperCalcemia: altered mental status, renal insufficiency

-Renal Insufficiency: light chan nephropathy (and tubules), amyloid, uric acid, hypercalcemia, infection

-Anemia

-Bone Destruction: pain, fractures, spinal cord compression

-CRAB has to be present for the diagnosis of a multiple myeloma

Others: hypogammaglobulinemia, amyloidosis, hyperviscosity

Question 3

What is an M spike?

Answer 3

• monoclonal protein in the serum or urine, from overproduction of one specific anti-body produced by the malignant plasma cell
• Will cause Rouleaux formation of the RBCs (line of coins)

Question 4

What does an IFE tell you?

Answer 4

Immuno-Fixation Electrophoresis

-It will tell you what kind of anti-body it is (heavy and light chain)

Question 5

Describe the mechanism of bone destruction in myeloma.

Answer 5

• myeloma cells produce DKK1, leading to increased RANKL and IL6 by osteoblast progenitor cells and marrow stromal cells
• Osteoblast differentiation is blocked and osteoclast muturation is stimulated
• Osteoclasts break down bone

Question 6

Name the worst prognostic chromosome abnormality in Myeloma.

Answer 6

• People with Del 17p do the worst
• t(4;14) and t(14;16) are also high risk

Question 7

Stage a myeloma with Durie Salmon and ISS.

Answer 7

• Durie-Salmon:
• Stage 1: Hgb>10g/dl, Ca normal, Normal skeletal survey or solitary plasmacytoma, low M protein w/ IgG<5 or IgA<3, Bence Jones <4
• Stage 2: Neither 1 or 3
• Stage 3 (one or more of the following): Hgb<8.5, Ca>12, High M component w/ IgG>7 or IgA.5, Bence Jones>12g/24hr, multiple lytic lesions
• ISS STAGING
• Stage 1: beta2 Mycroglobulin <3.5 and albumin >3.5 (survival median of 62 months)
• Stage 2: Beta2M <3.5 and albumin<3.5 or beta2M 3.5 to 5.5 (median survival of 44 months)
• Stage 3: B2M >5.5 (median survival 29 months)

Question 8

When is an autologous transplant indicated in myeloma?

Answer 8

• Generally eligable if pt is under 70 and in relatively good health (will have better chance to survive transplant)
• Allows high doses of chemo therapy (dose lim tox: BM suppression) and then give stem cells back to patient

Question 9

What two classifications of new drugs have changed the way we treat myeloma? Mechanism of action?

Answer 9

• IMiDs (immune modulatory drugs): ex is thalidomide and linolidomide, cause activation of T Cells, cause destruction of myeloma cells, alter stromal structure (VEGF decrease and IL-6). Have extracellular and intercellular activities on the myeloma cells. Very effective drugs for myeloma with minimal toxicity
• Proteosome Inhibitors: ex Bortezomib, inhibit protein destruction which leads to destruction of the myeloma cells

Question 10

Why do Waldenstrom patients become hyperviscous more commonly than myeloma patients?

Answer 10

• Walkdenstrom’s is b/t mult. myeloma and CLL/SLL and considered a low grade lymphoma which produces excess IgM paraprotein
• IgM is a bigger molecule so will cause hyperviscosity (serum viscosity >4) faster than overproduction of other abs

treat with Rituximab and Bortezumab

• Not a curable disease only treat if symptoms present
• Can only improve survival by treating patient when they are symptomatic, treating when asymptomatic will not prolong survival

Question 11

Name three causes of amyloidosis

Answer 11

(1) Light Chain Amyloidosis: can be primary or secondary to myeloma, involves nervous system, Heart, GI and liver
(2) Transthyretin: Familial, same systemic involvment as light chain, cause by enzyme defect
(3) Amyloidosis AA: due to chronic inflamm disorders, renal disease, hepatic and GI involvement

Prognosis: 1-2 yrs with standard treatment, possibly longer with transplant

Question 12

Monoclonal gammaopathy of Undetermined significance (MGUS)

Answer 12

>Precursor to Mult Myeloma, more common also

>Less than 10% plasma cells in the bone marrow

>Rate of progression to mult is 1%/yr

• Other Igs usually normal
• Increase in protein suggest progression towards malignancy
• Less likely to have Bence Jones proteinuria

absense of CRAB (so cant be myeloma)

Question 13

Smoldering Myeloma

Answer 13

Serum monoclonal protein > 3gm/dl and/or BM plasma cells >/= 10%

• NO CRAB***
• Do not treat, it wont help, can treat symptoms