26- Multiple Myeloma

Question 1

what is multiple myeloma?

Answer 1

tumour originating in bone marrow

characterised by abnormal proliferation of plasma cells in bone marrow = overproduction of monoclonal antibodies - can lead to bone destruction, anaemia and impaired immune function

Question 2

multiple myeloma - presentation?

Answer 2

initially asymptomatic, symptoms develop later

bone pain
bleeding – from affected platelet production
frequent infections – from loss of WBCs
anaemia – from loss of RBCs

Question 3

multiple myeloma - cause?

Answer 3

unknown aetiology, no causative mutations

Question 4

multiple myeloma - risk factors?

Answer 4

obesity
radiation exposure, exposure to certain chemicals/ carcinogens
family history

Question 5

multiple myeloma - list three main effects?

Answer 5

suppression of normal bone marrow, blood cell and immune cell function

bone resorption and release of calcium

pathological effects of paraprotein

Question 6

describe the effects of loss of bone marrow function in multiple myeloma

Answer 6

loss of bone marrow function = loss of RBCs, WBCs, immune cells and platelet production and function

• non functional WBCs/ myeloma cells don’t recognise foreign antigens = don’t produce functional antibodies = loss of immune system function
• anaemia = loss of RBCs
• recurrent infections = loss of WBCs
• bleeding tendencies = affected platelet function

Question 7

describe how bone resorption and release of calcium occurs in multiple myeloma - its effects?

Answer 7

myeloma cancerous plasma cells produce IL-6 = attracts stromal cells from bone marrow which produce RANKL

RANKL activates osteoclasts - encourage bone resorption and the breakdown of bone tissue

calcium is released into blood = hypercalcaemia

effects:
- mental illness
- bone weakness
- aberrant NS function as calcium is a NT

Question 8

what is paraprotein?

Answer 8

abnormal monoclonal Ig (antibody) produced by myeloma cells

Question 9

describe the pathological effects of paraprotein in multiple myeloma

Answer 9

high levels of paraprotein suggest malignancy

precipitation of paraprotein in kidney tubule= renal failure

deposition of paraprotein as amyloid in various tissues = clumps together, forms blockages/ plaques, leads to organ dysfunction

high levels can cause hyper-viscosity syndrome = increased viscosity of blood/ blood is thicker, doesn’t flow as well = risk of strokes and heart failure

Question 10

multiple myeloma - list different methods of diagnosis?

Answer 10

serum electrophoresis for paraprotein
urine electrophoresis for paraprotein
bone marrow biopsy
erythrocyte sedimentation rate/ ESR
flow cytometry and cytogenetics
radiological investigations

Question 11

multiple myeloma - describe different methods of diagnosis?

Answer 11

serum electrophoresis for paraprotein in blood
- paraprotein sequence is the same between people, can be run on gel for detection

urine electrophoresis for paraprotein

bone marrow biopsy
- assess levels of plasma cells in bone marrow = elevated in multiple myeloma, rapid division can be seen

erythrocyte sedimentation rate/ ESR
- elevated ESR from stacking RBCs, and RBCs sticking to the side with hyper-viscosity syndrome

flow cytometry
- analyse associated genetic abnormalities, identify specific markers associated with multiple myeloma

radiology/ imaging techniques
- detect skeletal abnormalities from bone resorption, bone looks thinner from bone loss

Question 12

list different treatment methods

Answer 12

radiotherapy
chemotherapy combinations
targeted therapies
immunotherapy = CAR-T
allogenic haemopoietic stem cell transplant (ASCT) in young patients

Question 13

chemotherapy combinations for multiple myeloma?

Answer 13

various drug combinations – e.g. thalidomide, lenalidomide, bortezomib – to kill cancer cells or inhibit their growth

Question 14

describe targeted therapies for multiple myeloma

Answer 14

drugs that specifically target proteins or pathways involved in growth/ survival of cancer cells

• proteasome inhibitor
• immunomodulatory drugs

Question 15

what is CAR-T as an immunotherapy for myeloma?

Answer 15

chimeric antigen receptor T-cell therapy

involves modifying a patient’s own functional immune cells to better recognise and attack cancer cells
- immune cells are exposed to a certain antigen and re-inserted into the patient to target cancer cells with that antigen

Question 16

what is allogenic haemopoietic stem cell transplant (ASCT)?

Answer 16

healthy SCs from donor (often a sibling) used to replace diseased bone marrow to restore normal function