Multiple myeloma

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Multiple myeloma

  1. 1. Multiple Myeloma
  2. 2. <ul><li>What is multiple myeloma? </li></ul>
  3. 3. <ul><li>It is a malignant disease of the plasma cells of bone marrow. </li></ul><ul><li>Remains an incurable disease . </li></ul>
  4. 4. <ul><li>What is the most common monoclonal protein found in MM? </li></ul>
  5. 5. <ul><li>IgG (55%) </li></ul><ul><li>IgA (20%) </li></ul><ul><li>In approximately 20% there is no paraproteinaemia, only light chains in the urine.(BJP) </li></ul>
  6. 6. <ul><li>What are the risk factors for MM? </li></ul>
  7. 7. <ul><li>Age >60. </li></ul><ul><li>Exposure to pesticides. </li></ul><ul><li>Radiation </li></ul><ul><li>Benzene </li></ul><ul><li>? Presence of IL-6 and HHV8 (Kaposi’s sarcoma Herpes Virus) </li></ul>
  8. 8. <ul><li>What are the clinical features of MM? </li></ul>
  9. 9. <ul><li>Disease of elderly. </li></ul><ul><li>Median age >60 </li></ul><ul><li>More common in black Africans. </li></ul><ul><li>Bone destruction </li></ul><ul><li>Renal failure </li></ul><ul><li>Bone marrow infiltration </li></ul>
  10. 10. <ul><li>May be symptomatic or asymptomatic. </li></ul><ul><li>Symptomatic myeloma characterized by presence of ROTI and CRAB. </li></ul><ul><li>Myeloma R elated O rgan or T issue I mpairment. </li></ul><ul><li>C alcium levels increased </li></ul><ul><li>R enal failure </li></ul><ul><li>A nemia </li></ul><ul><li>B one lesion </li></ul>
  11. 11. <ul><li>What is the cause for renal failure in MM? </li></ul>
  12. 12. <ul><li>Deposition of light chains in the tubules (most common). </li></ul><ul><li>Also: </li></ul><ul><li>hypercalcaemia, hyperuricaemia, use of NSAIDs (rarely) and deposition of amyloid. </li></ul>
  13. 13. <ul><li>What is the consequence of bone marrow infiltration with plasma cells? </li></ul>
  14. 14. <ul><li>anaemia </li></ul><ul><li>neutropenia </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Production of paraproteins. </li></ul>
  15. 15. <ul><li>What is the consequence of bone destruction in MM? </li></ul>
  16. 16. <ul><li>Fracture of long bones </li></ul><ul><li>Vertebral collapse </li></ul><ul><li>Hypercalcemia </li></ul>
  17. 17. <ul><li>What is the cause of spinal cord compression in MM? </li></ul>
  18. 18. <ul><li>Due to soft tissue plasmacytomas </li></ul>
  19. 19. <ul><li>In terms of cytogenetics which one has a better prognosis? </li></ul><ul><li>Hypodiploidy (<45 chromosomes) or </li></ul><ul><li>Hyperdiploidy (>50 chromosomes)? </li></ul>
  20. 20. <ul><li>Hyperdiploidy. </li></ul>
  21. 21. <ul><li>In MM which bone activity is increased? </li></ul><ul><li>Osteoblast or osteoclast? </li></ul>
  22. 22. <ul><li>Increased osteoclastic activity. </li></ul><ul><li>That is why biphosphonates is useful in MM because it inhibits osteoclastic activity. </li></ul>
  23. 23. <ul><li>Why do patients with MM get recurrent infections? </li></ul>
  24. 24. <ul><li>Because there is a reduction in the normal immunoglobulin levels ( immuneparesis ), contributing to the tendency for patients with myeloma to have recurrent infections. </li></ul>
  25. 25. <ul><li>What are the lab findings in MM? </li></ul>
  26. 26. <ul><li>FBC- normal or low. </li></ul><ul><li>ESR, CRP-almost always raised. </li></ul><ul><li>Blood film- Rouleaux formation , macrocytosis. </li></ul><ul><li>U&Es, Cr-renal failure </li></ul><ul><li>Serum B2 microglobulin >2.5mg/L. </li></ul><ul><li>Raised LDH </li></ul><ul><li>Serum calcium- normal or raised. </li></ul><ul><li>Serum ALP-normal </li></ul><ul><li>Total protein-normal or raised. </li></ul><ul><li>Serum albumin- normal or low. </li></ul><ul><li>SPE - monoclonal band. </li></ul><ul><li>Serum free light chain assay </li></ul><ul><li>Uric acid-normal or raised </li></ul><ul><li>24-hour urine electrophoresis and immunofixation is used for assessment of light-chain excretion. </li></ul><ul><li>Bone marrow aspirate or trephine shows characteristic infiltration by plasma cells .Amyloid may be found. </li></ul>
  27. 27. <ul><li>What are the imaging studies used to diagnose MM? </li></ul>
  28. 28. <ul><li>Skeletal survey-lytic lesion. easily seen in skull. </li></ul><ul><li>CT, MRI and PET are used in plasmacytomas (bone or soft tissue deposits). </li></ul><ul><li>Sestamibi- picks up bone dx missed on skeletal survey. </li></ul><ul><li>MRI spine- may show imminent compression/collapse. </li></ul>
  29. 29. <ul><li>Myeloma affecting the skull. Note the rounded lytic translucencies produced by infiltration of the skull with myeloma cells. </li></ul>
  30. 30. <ul><li>What are the stages of MM? </li></ul>
  31. 32. <ul><li>How do you diagnose MM? </li></ul>
  32. 33. <ul><li>Two out of three diagnostic features should be present: </li></ul><ul><li>paraproteinaemia or Bence Jones protein </li></ul><ul><li>radiological evidence of lytic bone lesions </li></ul><ul><li>an increase in bone marrow plasma cells. </li></ul>
  33. 34. <ul><li>What is the treatment for MM? </li></ul>
  34. 35. <ul><li>supportive care </li></ul><ul><li>chemotherapy </li></ul><ul><li>Autologous or allogeneic stem cell transplantation. </li></ul>
  35. 36. <ul><li>What is the supportive therapy? </li></ul>
  36. 37. <ul><li>Treat the anemia-erythropoetin helps. </li></ul><ul><li>Treat the infection </li></ul><ul><li>Radiotherapy/sytemic chemo/high dose dex for bone pain. </li></ul><ul><li>Kyphoplasty and vertebroplasty for treating vertebral fractures. </li></ul><ul><li>Biphosphonates (pamidronate/zoledronic acid)- beware of osteonecrosis of the jaw. </li></ul>
  37. 38. <ul><li>What are the chemo options? </li></ul><ul><li>For Elderly? </li></ul><ul><li>For Younger patients? </li></ul>
  38. 39. For elderly <ul><li>If not fit for transplant, treat with Melphalan + Prednisone + Thalidomide (MPT). </li></ul><ul><li>Beware: </li></ul><ul><li>Melphalan +prednisone = stem cell toxicity. </li></ul><ul><li>(only use in non-transplant candidate) </li></ul><ul><li>Melphalan-nephrotoxic. </li></ul>
  39. 40. For younger patients <ul><li>High-dose dexamethasone based induction . </li></ul><ul><li>Followed by high-dose melphalan with peripheral blood stem cell rescue (autotransplantation) </li></ul><ul><li>Stem cell transplant- improves survival but not curative . </li></ul><ul><li>CR in 40%. </li></ul><ul><li>median survival increasing to 6 years. </li></ul>
  40. 41. <ul><li>What agents to use for relapse myeloma? </li></ul>
  41. 42. <ul><li>Thalidomide (immunomodulatory derivatives) </li></ul><ul><li>Lenalidomide + dexamethasone. </li></ul><ul><li>(the above combination is more effective than high-dose dexamethasone alone in relapsed or refractory multiple myeloma-NEJM) </li></ul><ul><li>Bortezomib (proteosome inhibitor)- higher incidence of herpes zoster. </li></ul><ul><li>78% improvement in median time to progression with Bortezomib. </li></ul><ul><li>Choice based on side effect profile. </li></ul>
  42. 43. <ul><li>What are the prognostic markers of MM? </li></ul>
  43. 44. Bad prognosis if… <ul><li>Raised B2-microglobulin >4. </li></ul><ul><li>Low serum albumin <3g/dl. </li></ul><ul><li>Cytogenetics – ch13 deletion, hypodiploidy, T(4:14) </li></ul><ul><li>Raised LDH, CRP, Cr. </li></ul><ul><li>Low platelet <150 and Hb<100. </li></ul><ul><li>Bone marrow plasma cell percentage ≥ 50% </li></ul><ul><li>Age >70. </li></ul>
  44. 45. <ul><li>What features would make you suspect MGUS? </li></ul>
  45. 46. MGUS <ul><li>Monoclonal Gammapathy of Undetermined Significance. </li></ul><ul><li>Asymptomatic patient. Advanced age. </li></ul><ul><li>Presence of low serum M-protein <3 g/dL </li></ul><ul><li>No evidence of myeloma. </li></ul><ul><li>Minimal infiltrate of bone marrow (<10%) </li></ul><ul><li>IgG most common (70%). </li></ul><ul><li>BJP negative (69%) </li></ul><ul><li>Overall risk of progression= 1% per year. </li></ul><ul><li>No treatment is required. </li></ul>
  46. 47. <ul><li>What is the most important risk factor for progression of MGUS to plasma cell cancer? </li></ul>
  47. 48. <ul><li>M band size . The bigger, the worse. </li></ul><ul><li>IgM or IgA monoclonal protein has increased risk. </li></ul>
  48. 49. <ul><li>If a patient is found to have high levels of IgM paraprotein? </li></ul><ul><li>What is the most likely diagnosis? </li></ul>
  49. 50. <ul><li>Waldenstrom Macroglobulinemia. </li></ul>
  50. 51. <ul><li>What are the side effects of Thalidomide? </li></ul>
  51. 52. <ul><li>Constipation </li></ul><ul><li>Somnelence. </li></ul><ul><li>Painful neuropathy- major side effect. </li></ul>

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