Multiple Myeloma

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An Overview of Multiple Myeloma

Published in: Health & Medicine, Technology

Multiple Myeloma

  1. 1. Dr. Alan Teh , 2012
  2. 2. Sarah Newbury, the first reported patient with multiple myeloma. A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur.
  3. 3. Timeline depicting the history and treatment of multiple myeloma from 1844 to the present. Kyle R A , Rajkumar S V Blood 2008;111:2962-2972
  4. 4.  Myeloma is a blood cancer  Incidence : 0.7M/0.5 F per 100,000 population (NCR, 2003)  Median age: 60 years  1/10 as common as leukaemias
  5. 5.  Is not known for sure  Decline in the immune system  Biological factors  Certain occupations  Exposure to certain chemicals  Exposure to radiation  Virus
  6. 6. 7  Cancer of plasma cells.  Plasma cells come from B lymphocytes, and produce antibodies (immunoglobulins).  Myeloma cells produce abnormal immunoglobulins. – Overproduce monoclonal protein or paraprotein. – Ineffective immunoglobulins. – Leads to decreased bone marrow function. – Destruction of bone tissue.
  7. 7.  Plasma cell proliferation - > anemia, bone marrow suppression, infection risk  Osteoclasts - > boney lesions, fractures, increased blood calcium  Paraprotein, hypercalcemia -> renal failure  Hypercalcemia – polyuria, thirst, drowsiness, coma
  8. 8.  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  Early stage - asymptomatic
  9. 9. 14  Skull  Spine  Thoracic  Lumbar  Vertebrae  Pelvis  Long bones  Spinal cord – compression can occur http://www.emedicine.com/Radio/topic460.htm#section~Introduction
  10. 10.  MGUS Monoclonal Gammopathy of Unknown Significance  Asymptomatic myeloma  Symptomatic myeloma
  11. 11. Risk group Relative Risk Risk @ 20 yrs Lowest risk: 1. M protein < 1.5 g/dL 2. IgG subtype 3. Normal FLC ratio 1 5% Any 1 factor abnormal 5.4 21% Any 2 factors abnormal 10.1 37% All 3 factors abnormal 20.8 58% Rajkumar, V et al. Blood . 2005
  12. 12. When I told a friend that I have cancer, he replied "I thought you were an Aries?".
  13. 13.  hyperCalcaemia  Renal insufficiency  Anaemia  Bone lesions
  14. 14.  Paraprotein (M-protein) serum protein electrophoresis 24 hr urine protein electrophoresis serum Free light chain  Bone marrow biopsy plasma cells chromosome analysis: Karyotyping, FISH  Imaging X Rays, MRI, PET scan
  15. 15. Cytogenetics
  16. 16. FISH
  17. 17. Normal Skull Xray
  18. 18. International staging system (ISS)  Stage I — B2M <3.5 mg/L and serum albumin ≥3.5 g/dL  Stage II — neither stage I nor stage III  Stage III — B2M ≥5.5 mg/L Median overall survival for patients with ISS stages I, II, and III are 62, 44, and 29 months
  19. 19.  High risk (median survival 25 months):  Intermediate risk (median survival 42 months)  Standard risk (median survival 50 months)
  20. 20. What's the difference between God and a doctor God doesn't think he’s a doctor
  21. 21. Cancer cures smoking, eventually
  22. 22. 34 • Currently incurable in most patients. • Long-term complete responses are rare. • Median survival with standard therapy about 3 years. • Autologous stem cell transplant may prolong progression free survival, but it’s not curative. • Treatment of relapse: – No standard therapy. – Existing options inadequate. New treatment options needed.
  23. 23. 35  Conventional chemotherapy:  Melphalan  Doxorubicin  Cyclophosphamide • Radiation therapy • Stem cell transplantation: – Autologous – Allogenic • Novel therapeutics: – Thalidomide – Lenalidomide – Bortezomib Thalomid® Prescribing Information, Revlimid® Prescribing Information; Velcade® Prescribing Information • Steroid therapy: – Dexamethasone – Prednisone
  24. 24.  Indications for treatment  Risk stratification - age - co-morbidities  Eligibility for stem cell transplantation
  25. 25.  Deferral of chemotherapy until progression to symptomatic disease  Follow these patients closely, every 3 to 4 months, with serum protein electrophoresis, complete blood count, serum creatinine, and serum calcium  Metastatic bone survey should be considered annually because asymptomatic bone lesions may develop
  26. 26.  Anemia (hemoglobin <10 g/dL or 2 g/dL below normal)  Hypercalcemia (serum calcium >11.5 mg/dL)  Renal insufficiency (serum creatinine>2 mg/dL)  Lytic bone lesions or severe osteopenia  Extramedullary plasmacytoma
  27. 27.  Conventional chemotherapy  Survival ≤ 3 yrs  Transplantation  Prolongs survival 4-5 yrs  Novel agents targeting stromal interactions and associated signaling pathways have superiority over conventional chemotherapy - increased % total responders - increased depth of response
  28. 28.  Era of Novel therapy as frontline > Conventional chemotherapy  Autologous transplantation (high dose chemotherapy and stem cell rescue) still an option for younger patients
  29. 29.  Examples of current Novel agent combinations:  Thalidomide based : TD, CTD, MPT  Bortezomib (Velcade) based: Vdex, VMP, CVD, PAD, VRD  Lenalidomide (Revlimid) based: LenDex, Lendex
  30. 30.  Younger patients  Timing  Upfront after initial therapy with novel agents  Salvage for relapse  Single vs Tandem (Double)  Low TRM - <3%
  31. 31.  Age >70 years  Significant comorbities (organ function)  Poor performance status
  32. 32.  Generally not recommended (outside of clinical trials)  High incidence of GVHD  High TRM (> 40%)
  33. 33.  Radiotherapy  Surgery  Bone care – bisphosphonates  Transfusions  Growth factors  Treatment and prevention of infections  Monitoring, management and prevention of s/e
  34. 34.  Unexpected new long-term complications  Second cancers  Long-term maintenance for survivors: quality of life  Family/social problems  Financial/insurance concerns  Other
  35. 35. 50  MM patients are expected to live longer  Proper health maintenance contributes toward longer survival and quality of life
  36. 36.  Biochemical - significant increase in M-protein  Clinical - CRAB criteria  Importance of monitoring and follow-up
  37. 37. New drugs on the horizon  Carfilzomib  Pomalidomide  Panobinostat  Vorinostat  Elotuzumab Old drugs with new use  Bendamustine
  38. 38.  Be informed  http://myeloma.org  Group support meetings support groups  http://malaysianmedicine.com – Myeloma Support Group
  39. 39. Myeloma Info mobile application mobile browser: http://malaysianmedicine.com/myelomainfo

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