Multiple Myeloma

Question 1

Myeloma - Risk factors? (6)

Answer 1

Age

Male gender

Blacks

Exposure to Petroleum / nuclear radiation - has the patient worked in oil industry?.

Family history

MGUS

Obesity

Question 2

Multiple Myeloma - clinical features/presentation to Ask for? _(P_RICMCP)

Answer 2

CRAB + Cytopaenia + Constitutional symptoms.

Hypercalcaemia: history of stones, bone pain, psychological disturbances, abdominal pain/constipation.

Cytopaenia: anaemia, infection, bleeding

Renal impairment

Bone pain/fractures

Constitutional: weight loss, fatigue.

Question 3

How would you work up a suspected multiple myeloma?

Answer 3

1. Confirm the Diagnosis:

Serum/Urine PEP + Immunofixation looking for monoclonal (M) protein and suppression of involved Igs

Serum FLC looking for abnormal K/L ratio (normal 0.26-1.65), also if FLC ratio >100 → greater risk of end-organ danage, and 20% of MM is light-chain disease

24H urine collection for BJP

Ultimately will need BMAT, looking for >10% clonal plasma cells

2. Look for complications

Look for evidence of CRAB: CMP, EUC, FBC**, Skeletal survey/cross sectional imaging: **low-dose CT (look for lytic lesions: if -ve or suspicious of spine involvement - consider MRI)

3. Prognosticate

• LDH + B2M
• BM: Cytogenetic/FISH cytogenetics (e.g. t(4:14)-bad prognosis)

Question 4

Complications of multiple myeloma? (6)

Answer 4

Anaemia

Bleeding tendency - paraproteins inactivate procoagulants, and reduce platelet function by coating it with Abs.

Infection (Ig dysfunction)

spinal cord compression

Fracture

Amyloid

Question 5

Is bone scan useful for multiple myeloma diagnosis?

Answer 5

No. Modalities are CT, MRI and PET.

Question 6

Define Smouldering myeloma and MGUS.

Answer 6

• Smouldering myeloma: Paraprotein >= 30g/L OR bone marrow plasma cells >10% OR urinary monoclonal protein >= 500mg/ 24hr. 10% progress to myeloma
• MGUS: paraprotein <= 30g/L and BM plasma cells <10%, 1% progress however size of M band related to progression risk
• In either case, there is no CRAB

Question 7

DDx for Paraprotein?

(6)

Answer 7

Haematological

MM

MGUS

Waldenstrom’s

Amyloid (AL)

CLL, NHL

Non-haematological

Hep C

Autoimmune diseases

Chronic infection

Question 8

Myeloma staging (what is it based on?) and prognosis? (3)

Answer 8

Stage 1: B2M <3.5mg/L + Albumin >35 ⇒ 5 yrs

Stage 2: in between ⇒ 4 yrs

Stage 3: B2M >5.5 ⇒ 3 yrs

Overall median survival: 3-5 years

Question 9

What are the causes of Anaemia in patients with multiple myeloma? (5)

Answer 9

BM infiltration

Bleeding

ACD

Renal failure

Therapy side effects

Question 10

Myeloma Clinical Examinations (6)

Answer 10

Anaemia, Cachexia

Echymoses/Purpura

Signs of infection

Lymphadenopathy

Bony tenderness & signs of spinal cord compression

Ask for UA and temperature.

Question 11

What are general management strategy (except for chemotherapy) in patients with multiple myeloma?

Answer 11

Goals: minimise symptoms, prevent complications, slow disease progression

Non-pharm

• Education
• Symptom management: EPO, Irradiation for localised bone pain / spinal cord compression
• Prevent renal failure: adequate hydration, bicarbonate for BJP-proteinuria, minimise use of IV contrast / make sure pre-hydrated.
• Infection prophylaxis: hygiene, avoiding contact, vaccinate (inactivated, not live-attenuated)

Pharm

• Bisphosphonates as bone protection
• Consider surgical correction for Lytic lesions
• Chemotherapy: induction followed by maintenance
• autologous/allogenic SCT

Is the patient candidate for transplant?

Follow-up

Monitor disease with paraprotein, SFLC, PET scan to look for disease

Question 12

Describe a suitable candidate for autograph transplant in multiple myeloma? (3)

Answer 12

Younger (<70), although physiological age is more important than biological

Low ECOG

Few comorbidities

Question 13

Pharmacological Tx strategy for Transplant-eligible MM patients?

Answer 13

Induction: CyBORD (cyclophosphamide, Bortezomib, Dexamethasone) or

CDT (cyclophosphamide, Dex, Thalidomide)

3-6 cycles, then

Autologous SCT, then

Maintenance thalidomide or lenalidomide until progression or intolerance

Question 14

Describe a suitable pharmacological Tx strategy for transplantation-ineligible MM patients?

Answer 14

MTP or MBP (mephalan, thalidomide, pred, bortezomib). Can consider 2 drug regimes (e.g. Bortezomib + Dex or Lenalidomide + Dex.

6-12 cycles, then

maintenance Lenalidomide until progression or intolerance

Question 15

Main side effects of Anti-myeloma therapies? (3)

Answer 15

Peripheral neuropathy (thalidomide, Bortezomib, lenalidomide) - painful PN.

VTE risk (especially thalidomide)

Secondary malignancies (especially Lenalidomide)

Question 16

Should alkylating agents be used for this patients with MM? (e.g. cyclophosphamide, mephalan)

Answer 16

If the patient has Renal impairment or being considered for autologous transplant, bortezomib is preferred.