Multiple myeloma (MM)

Question 1

Multiple myeloma

Answer 1

Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. The plasma cells proliferate in the bone marrow and often results in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures.

Question 2

Clinical presentation

Answer 2

●Anemia – 73 percent
●Bone pain – 58 percent
●Elevated creatinine – 48 percent
●Fatigue/generalized weakness – 32 percent
●Hypercalcemia – 28 percent
●Weight loss – 24 percent, one-half of whom had lost ≥9 kg

Question 3

CRAB

Answer 3

Calcium
Renal failure
Anemia
Bone lesions

Question 4

Pathologic features

Answer 4

The vast majority (97 percent) of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells, which can be detected by protein electrophoresis of the serum (SPEP) and/or of an aliquot of urine (UPEP) from a 24-hour collection

As mentioned above, patients with MM frequently present with renal insufficiency due to cast nephropathy.

The most frequent findings on peripheral smear are rouleaux formation

A bone marrow aspirate and biopsy are a key component to the diagnosis of MM

Question 5

Myeloma Subtypes

Answer 5

●IgG – 52 percent
●IgA – 21 percent
●Kappa or lambda light chain only (Bence Jones) – 16 percent
●IgD – 2 percent
●Biclonal – 2 percent
●IgM – 0.5 percent
●Negative – 6.5 percent

Question 6

Staging of MM

Answer 6

●Stage I — B2M <3.5 mg/L + serum albumin ≥3.5 g/dL
●Stage II — neither stage I nor stage III
●Stage III — B2M ≥5.5 mg/L

Question 7

Investigations

Answer 7

blood count
beta 2 microglobulin
calcium level
24 hour urine collection
bence jones proteins

serum protein electrophoresis
free light chain assay - performed on urine

skeletal survay
bone marrow biopsy

Question 8

Treatment of symptomatic MM

Answer 8

Determine if auto stem cell candidate

SCT candidate:

Induction with bortezomib, lenalidomide/thalidomide, low-dose dexamethasone

maintenance with lenalidomide/thalidomide, low-dose dexamethasone

or bortezomib based maintenance

Can try two rounds of Auto SCT
non curative

Not SCT candidate:

induction with melphalan and prednisolone with either thalidomide or bortezomib

maintenance with thalidomide and dexamethasone

Question 9

Tracking response to therapy in MM

Answer 9

The preferred method is the measurement of monoclonal (M) protein in serum and urine

Question 10

Treatment of Hypercalcemia in MM

Answer 10

Hypercalcemia

●Hydration, dexamethasone as part of myeloma therapy or prednisone (1 mg/kg per day) is effective in most cases of mild hypercalcemia (eg, serum calcium <12 mg/dL).
●In moderate to severe hypercalcemia (eg, serum calcium >14 mg/dL), treatment includes hydration, corticosteroids, and a bisphosphonate such as zoledronic acid or pamidronate.

Calcitonin is used if rapid reduction of calcium levels is needed or if patients are refractory to bisphosphonates alone.

Question 11

Treatment of Bone lesions in MM

Answer 11

be as active as possible in order to maintain bone density

bisphosphonate therapy

stabilization with an intramedullary rod. Although the decision to stabilize lytic lesions is made by an orthopedic surgeon and depends in part upon the location of the lesions, a usual rule of thumb is that if there is 50 percent or more destruction of cortical bone thickness, surgical fixation is required.

Radiation — Up to 40 percent of patients with myeloma will require radiation to control disease at some point in their disease course. Common indications for radiation therapy include:

●Pain control of lytic lesions that are refractory to systemic therapy.
●Treatment of spinal cord compression from plasmacytoma.

Question 12

Bortezomib

Answer 12

inhibits proteosome function.
leads to build up of non functioning protein leading to cell apoptosis

side effect: associated with peripheral neuropathy

Question 13

thalidomide / lenalidomide

Answer 13

The precise mechanism of action for thalidomide is unknown

inhibits cereblon
inhibits anigogenesis

side effects:

oedema
teratogenic
leukopenia

Question 14

zoledronic acid

Answer 14

bisphosphonate drug given to treat some bone diseases which result in risk of fracture

Zoledronic acid slows down bone resorption, allowing the bone-forming cells time to rebuild normal bone and allowing bone remodeling

side effects:

osteonecrosis of the jaw
renal impairment