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Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida Monoclonal Gammopathy of Undetermined  Significance and Smoldering Multiple Myeloma Robert A. Kyle, MD Professor of Medicine Mayo Clinic
MGUS  Olmsted County MN ,[object Object],[object Object],[object Object],[object Object],[object Object]
MGUS OLMSTED COUNTY, MN ,[object Object],[object Object],[object Object],Kyle et al., New Engl J Med, 2006, 354:1362
MGUS Olmsted County MN CP1118008-35 Age No. No. % 50 – 59   8,373 141 1.7 60 – 69    6,019 178 3.0 70 – 79   4,508 205 4.6 ≥ 80   2,563 170 6.6 Total 21,463 694 3.2 ≥  70 7,071 375 5.3 M-protein Kyle et al., New Engl J Med, 2006, 354:1362
Age (yr)   Prevalence of MGUS (%)   Prevalence of MGUS According to Age Kyle et al., New Engl J Med, 2006, 354:1362
MGUS in African Americans ,[object Object],[object Object],[object Object],[object Object],[object Object]
MGUS SE Minnesota Jan 1, 1960-Dec 31, 1994 CP1118008-24 Male (%) 54 Age (med years) 72 <40 years (%)   1.7 M-spike (g/dL-med)   1.2 n=1,384 Kyle, et al., New Engl J Med, 346:564, 2002
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],MGUS SE  MINNESOTA Kyle, et al., New Engl J Med, 346:564, 2002
MGUS SE Minnesota 1960-1994 n=1,384 12% 25% 30% First progression Full progression 10% 21% 26% Cumulative probability (%) Years 1,384 Patients at risk (no.) 867 423 177 56 17 CP1022686-6 Kyle, et al., New Engl J Med, 346:564, 2002
Full Progression or Death CP971723- 6 Cumulative incidence (%) Years 6% Progression Death 10% 11% 53% 72% 76% Kyle, et al., New Engl J Med, 346:564, 2002
Relative Risk of Full Progression by Serum M-Spike Size Serum m-spike value CP999081-2 Relative risk of full progression Probability of full progression at 20 years (%) 13.6 15.6 41.2 48.8 24.6 64 Kyle, et al., New Engl J Med, 346:564, 2002 0.5 1.0 1.5 2.0 2.5 3.0 13.6 25 50 65 3 9 5 7 1
MGUS and Free Light Chain (FLC) Rajkumar, et al., Blood; 106:1148, 2005 18 37 10.1 226 2 risk factors, abn Competing risk Absolute 27 10 2 58 20.8 53 3 risk factors, abn 21 5.4 420 1 risk factor, abn 5 1 449 M-protein < 1.5 g/dl,   IgG, Normal FLC Risk of Prog 20 yr % RR 95% CI N
Smoldering Multiple Myeloma ,[object Object],[object Object],[object Object],[object Object],[object Object]
Smoldering Multiple Myeloma ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Smoldering Multiple Myeloma ,[object Object],[object Object],[object Object],[object Object]
years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to Multiple Myeloma or Amyloid 51% 66% 73% 78%
years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS
MGUS and SMM ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
MGUS and SMM ,[object Object]
MGUS/SMM Subcommittee ,[object Object],[object Object],[object Object],[object Object]
MGUS Question  ,[object Object],[object Object],[object Object]
SMM Question ,[object Object],[object Object],[object Object]

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MGUS SMM Risk Factors Progression Monitoring Treatment

  • 1. Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma Robert A. Kyle, MD Professor of Medicine Mayo Clinic
  • 2.
  • 3.
  • 4. MGUS Olmsted County MN CP1118008-35 Age No. No. % 50 – 59 8,373 141 1.7 60 – 69 6,019 178 3.0 70 – 79 4,508 205 4.6 ≥ 80 2,563 170 6.6 Total 21,463 694 3.2 ≥ 70 7,071 375 5.3 M-protein Kyle et al., New Engl J Med, 2006, 354:1362
  • 5. Age (yr) Prevalence of MGUS (%) Prevalence of MGUS According to Age Kyle et al., New Engl J Med, 2006, 354:1362
  • 6.
  • 7. MGUS SE Minnesota Jan 1, 1960-Dec 31, 1994 CP1118008-24 Male (%) 54 Age (med years) 72 <40 years (%) 1.7 M-spike (g/dL-med) 1.2 n=1,384 Kyle, et al., New Engl J Med, 346:564, 2002
  • 8.
  • 9. MGUS SE Minnesota 1960-1994 n=1,384 12% 25% 30% First progression Full progression 10% 21% 26% Cumulative probability (%) Years 1,384 Patients at risk (no.) 867 423 177 56 17 CP1022686-6 Kyle, et al., New Engl J Med, 346:564, 2002
  • 10. Full Progression or Death CP971723- 6 Cumulative incidence (%) Years 6% Progression Death 10% 11% 53% 72% 76% Kyle, et al., New Engl J Med, 346:564, 2002
  • 11. Relative Risk of Full Progression by Serum M-Spike Size Serum m-spike value CP999081-2 Relative risk of full progression Probability of full progression at 20 years (%) 13.6 15.6 41.2 48.8 24.6 64 Kyle, et al., New Engl J Med, 346:564, 2002 0.5 1.0 1.5 2.0 2.5 3.0 13.6 25 50 65 3 9 5 7 1
  • 12. MGUS and Free Light Chain (FLC) Rajkumar, et al., Blood; 106:1148, 2005 18 37 10.1 226 2 risk factors, abn Competing risk Absolute 27 10 2 58 20.8 53 3 risk factors, abn 21 5.4 420 1 risk factor, abn 5 1 449 M-protein < 1.5 g/dl, IgG, Normal FLC Risk of Prog 20 yr % RR 95% CI N
  • 13.
  • 14.
  • 15.
  • 16. years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to Multiple Myeloma or Amyloid 51% 66% 73% 78%
  • 17. years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS years from diagnosis percent 0 5 10 15 20 25 0 20 40 60 80 100 Progression to MM or AL 14% 32% 39% 54% 43% 63% 70% 70% 70% 78% 88% 4% 10% 16% 21% M-spike>=3 & BMPC>=10 M-spike< 3 & BMPC>=10 M-spike>=3 & BMPC<10 MGUS
  • 18.
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  • 21.
  • 22.