Multiple Myeloma Modified , Dr Gamal Abdul Hamid
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Multiple myeloma
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Multiple Myeloma Modified , Dr Gamal Abdul Hamid
- 1. Multiple Myeloma Gamal Abdul Hamid MD
- 18. Bone marrow aspirate demonstrating plasma cells of multiple myeloma. Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone
- 19. Bone marrow biopsy demonstrating sheets of malignant plasma cells in multiple myeloma
- 24. Staging: Durie-Salmon system: widely used since 1975 Stage based on M-protein levels, bone lesions, Hb values, serum calcium—many variables International Staging System Simplified staging based on serum β 2-microglobulin Stage International Staging System Criteria I β 2 -microglobulin < 3.5; albumin ≥ 3.5 II Neither stage I nor stage III values III β 2 -microglobulin > 5.5
- 28. Disease Phases Asymptomatic Symptomatic MGUS or Smouldering Myeloma Active Myeloma Relapse Refractory relapse Plateau remission Therapy IIII IIII IIII M Protein g/dL Go!
- 31. 1960 1970 1980 1990 2000 Melphalan MP MEDIAN OS 3 years First reports on High-dose Treatment 1983 VAD 1984 ASCT 1996 Thalidomide 1999 Double ASCT > single 2003 Bortezomib 2004 Median OS Lenalidomide 2005 not reached at 7 years History Of MM Treatment
- 37. VISTA : VELCADE as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone San Miguel et al. ASH 07 VMP Cycles 1-4 Bortezomib 1.3 mg/m 2 IV: days 1,4,8,11,22,25,29,32 Melphalan 9 mg/m 2 and prednisone 60 mg/m 2 days 1-4 Cycles 5-9 Bortezomib 1.3 mg/m 2 IV: days 1,8,22,29 Melphalan 9 mg/m 2 and prednisone 60 mg/m 2 days 1-4 MP Cycles 1-9 Melphalan 9 mg/m 2 and prednisone 60 mg/m 2 days 1-4 9 x 6-week cycles (54 weeks) in both arms Primary endpoint: TTP Newly diagnosed MM patients; age >65 years
- 39. High CR rate with MPV VISTA : Response to Treatment MPV MP P CR + PR CR+VGPR 82% 45% 50% 10% <.0001 <.0001 CR (IF-) 35% 5% <.0001
- 40. Thank you
- 41. Thank you
Editor's Notes
- exposed to the radiation of nuclear warheads in World War II after a 20-year latency
- (Only 2 to 3 percent of cases are reported in patients < 30 years)
- Two thirds of patients complain of bone pain, frequently located in the back, long bones, skull and pelvis. Patients with multiple myeloma commonly present with lower back pain.
- tubular damage associated with the excretion of light chains is almost always present. Normally, light chains are filtered, reabsorbed in the tubules, and catabolized. With the increase in the amount of light chains presented to the tubule, the tubular cells become overloaded with these proteins, and tubular damage results either directly from light chain toxic effects or indirectly from the release of intracellular lysosomal enzymes . The earliest manifestation of this tubular damage is the adult Fanconi syndrome (a type 2 proximal renal tubular acidosis), with loss of glucose and amino acids, as well as defects in the ability of the kidney to acidify and concentrate the urine The proteinuria is not accompanied by hypertension, and the protein is nearly all light chains. Generally, very little albumin is in the urine because glomerular function is usually normal . When the glomeruli are involved, the proteinuria is nonselective Patients with myeloma also have a decreased anion gap [i.e., Na+– (Cl–+ HCO3–) because the M component is cationic, resulting in retention of chloride. This is often accompanied by hyponatremia that is felt to be artificial (pseudohyponatremia) because each volume of serum has less water as a result of the increased protein. Myeloma patients are susceptible to developing acute renal failure if they become dehydrated.
- The serum M component will be IgG in 53% of patients, IgA in 25%, and IgD in 1%; 20% of patients will have only light chains in serum and urine. Dipsticks for detecting proteinuria are not reliable at identifying light chains, and the heat test for detecting Bence Jones protein is falsely negative in about 50% of patients with light chain myeloma.
- Total-body tumor burden is estimated to be low (stage I, <0.6 x 1012 cells/m2), intermediate (stage II, 0.6 to 1.2 x 1012 cells/m2), or high (stage III, >1.2 x 1012 cells/m2), and the stages are further subdivided on the basis of renal function [A if serum creatinine <177 mol/L (<2 mg/dL), B if >177 (>2). Patients in stage IA have a median survival of more than 5 years and those in stage IIIB about 15 months. 2-Microglobulin is a protein of 11,000 mol wt with homologies with the constant region of immunoglobulins that is the light chain of the class I major histocompatibility antigens (HLA-A, -B, -C) on the surface of every cell. Patients with 2-microglobulin levels <0.004 g/L have a median survival of 43 months and those with levels >0.004 g/L only 12 months. IL-6 may be an autocrine and/or paracrine growth factor for myeloma cells; elevated levels are associated with more aggressive disease.
- VMP DOR by Investigator: All responders 22.6 mo; CR = NE, PR = 16.2 months; MP: All responders 14.3 months; CR 16.7 months; PR 13.1 months VMP DOR by Investigator with 0.5 g/dL cut-off: All responders ??; CR = NE, PR = 22.4 months; MP: All responders ??: CR ??; PR ?? DOR p value 0.0012 for all responders, and 0.03 for patients with CR Progressive disease: 1% VMP vs 2% MP