Multiple Myeloma

• What is multiple myeloma?

• It is a malignant disease of the plasma cells of bone marrow.

• Remains an incurable disease.

• What is the most common monoclonal protein found in MM?

• IgG (55%)• IgA (20%)

• In approximately 20% there is no paraproteinaemia, only light chains in the urine.(BJP)

• What are the risk factors for MM?

• Age >60.• Exposure to pesticides.• Radiation• Benzene• ? Presence of IL-6 and HHV8 (Kaposi’s

sarcoma Herpes Virus)

• What are the clinical features of MM?

• Disease of elderly.• Median age >60• More common in black Africans.

• Bone destruction• Renal failure• Bone marrow infiltration

• May be symptomatic or asymptomatic.

• Symptomatic myeloma characterized by presence of ROTI and CRAB.

• Myeloma Related Organ or Tissue Impairment.

• Calcium levels increased• Renal failure• Anemia• Bone lesion

• What is the cause for renal failure in MM?

• Deposition of light chains in the tubules (most common).

Also:• hypercalcaemia, hyperuricaemia, use of

NSAIDs (rarely) and deposition of amyloid.

• What is the consequence of bone marrow infiltration with plasma cells?

• anaemia• neutropenia• Thrombocytopenia• Production of paraproteins.

• What is the consequence of bone destruction in MM?

• Fracture of long bones• Vertebral collapse• Hypercalcemia

• What is the cause of spinal cord compression in MM?

• Due to soft tissue plasmacytomas

• In terms of cytogenetics which one has a better prognosis?

• Hypodiploidy (<45 chromosomes) or• Hyperdiploidy (>50 chromosomes)?

• Hyperdiploidy.

• In MM which bone activity is increased?• Osteoblast or osteoclast?

• Increased osteoclastic activity.

• That is why biphosphonates is useful in MM because it inhibits osteoclastic activity.

• Why do patients with MM get recurrent infections?

• Because there is a reduction in the normal immunoglobulin levels (immuneparesis), contributing to the tendency for patients with myeloma to have recurrent infections.

What are the lab findings in MM?

• FBC- normal or low.• ESR, CRP-almost always raised.• Blood film- Rouleaux formation, macrocytosis.• U&Es, Cr-renal failure• Serum B2 microglobulin >2.5mg/L.• Raised LDH• Serum calcium- normal or raised.• Serum ALP-normal• Total protein-normal or raised.• Serum albumin- normal or low.• SPE- monoclonal band.• Serum free light chain assay• Uric acid-normal or raised• 24-hour urine electrophoresis and immunofixation is used for

assessment of light-chain excretion.• Bone marrow aspirate or trephine shows characteristic infiltration by

plasma cells .Amyloid may be found.

• What are the imaging studies used to diagnose MM?

• Skeletal survey-lytic lesion. easily seen in skull.• CT, MRI and PET are used in plasmacytomas

(bone or soft tissue deposits).• Sestamibi- picks up bone dx missed on skeletal

survey.• MRI spine- may show imminent

compression/collapse.

• Myeloma affecting the skull. Note the rounded lytic translucencies produced by infiltration of the skull with myeloma cells.

• What are the stages of MM?

• How do you diagnose MM?

Two out of three diagnostic features should be present:

• paraproteinaemia or Bence Jones protein• radiological evidence of lytic bone lesions• an increase in bone marrow plasma cells.

• What is the treatment for MM?

• supportive care • chemotherapy • Autologous or allogeneic stem cell

transplantation.

• What is the supportive therapy?

• Treat the anemia-erythropoetin helps.• Treat the infection• Radiotherapy/sytemic chemo/high dose dex

for bone pain.• Kyphoplasty and vertebroplasty for treating

vertebral fractures.• Biphosphonates (pamidronate/zoledronic

acid)- beware of osteonecrosis of the jaw.

• What are the chemo options?• For Elderly?• For Younger patients?

For elderly

• If not fit for transplant, treat with Melphalan + Prednisone + Thalidomide (MPT).

Beware: • Melphalan +prednisone = stem cell toxicity. (only use in non-transplant candidate)

• Melphalan-nephrotoxic.

For younger patients

• High-dose dexamethasone based induction.

• Followed by high-dose melphalan with peripheral blood stem cell rescue (autotransplantation)

• Stem cell transplant- improves survival but not curative.

• CR in 40%.• median survival increasing to 6 years.

• What agents to use for relapse myeloma?

• Thalidomide (immunomodulatory derivatives)

• Lenalidomide + dexamethasone. (the above combination is more effective than high-dose

dexamethasone alone in relapsed or refractory multiple myeloma-NEJM)

• Bortezomib (proteosome inhibitor)- higher incidence of herpes zoster.

• 78% improvement in median time to progression with Bortezomib.

• Choice based on side effect profile.

• What are the prognostic markers of MM?

Bad prognosis if…

• Raised B2-microglobulin >4.• Low serum albumin <3g/dl.• Cytogenetics –ch13 deletion, hypodiploidy,

T(4:14) • Raised LDH, CRP, Cr.• Low platelet <150 and Hb<100.• Bone marrow plasma cell percentage ≥ 50%• Age >70.

• What features would make you suspect MGUS?

MGUS• Monoclonal Gammapathy of Undetermined

Significance.• Asymptomatic patient. Advanced age.• Presence of low serum M-protein <3 g/dL• No evidence of myeloma.• Minimal infiltrate of bone marrow (<10%)• IgG most common (70%).• BJP negative (69%)• Overall risk of progression= 1% per year.• No treatment is required.

• What is the most important risk factor for progression of MGUS to plasma cell cancer?

• M band size. The bigger, the worse.

• IgM or IgA monoclonal protein has increased risk.

• If a patient is found to have high levels of IgM paraprotein?

• What is the most likely diagnosis?

• Waldenstrom Macroglobulinemia.

• What are the side effects of Thalidomide?

• Constipation• Somnelence.• Painful neuropathy- major side effect.