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Fifty Years of Progress and the Future of Myeloma

Fifty Years of Progress and the Future of Myeloma. Myeloma Research Roundtable Scottsdale, Arizona March 21, 2014 Robert A. Kyle, MD. Scottsdale, Arizona. Rochester, Minnesota. Jacksonville, Florida. CP1123175-1. Disclosures for Robert A. Kyle. None Related to this presentation.

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Fifty Years of Progress and the Future of Myeloma

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  1. Fifty Years of Progress and the Future of Myeloma Myeloma Research Roundtable Scottsdale, ArizonaMarch 21, 2014Robert A. Kyle, MD Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida CP1123175-1

  2. Disclosures for Robert A. Kyle None Related to this presentation.

  3. Multiple Myeloma Cecil Textbook of Medicine 7th Ed., 1948

  4. Lancet 2:388, 1947 CP1143748-20

  5. CP1143748-23

  6. Survival from Onset of Treatment of Multiple Myeloma Placebo Surviving(%) Urethane Months Blood 27(3):335, March 1966 CP1143748-24

  7. Electrophoresis Arne Tiselius • Discovered 4 bands in horse serum, 1937 – albumin, α, β, γ • Rejected by Biochemical Journal • Published in Transactions of the Faraday Society

  8. Electrophoresis • Cost: $5,000 • One technician, 1 day, 1 patient • 1951 Kunkel & Tiselius – filter paper electrophoresis

  9. Studies on Conditions Associated with Disturbed Gammopathies Globulin Formation Jan Waldenström Department of Medicine, University ofLund General Hospital, Malmõ, Sweden One of the important happenings in clinical, chemical pathology, and thus in medicine generally, has been the introduction of better methods for the fractionation of serum proteins. The old method of electrolyte precipitation was followed by the free electrophoresis of Tiselius (1937) in Uppsala, permitting… Harvey Lectures 56:211, 1961 CP1118008-5

  10. Gammopathy Concept • Monoclonal – Malignant or potentially malignant • Polyclonal – Reactive or inflammatory

  11. so easy it seemed Once found, which Yet unfound most Would have thought Impossible. CP1222613-1

  12. Jan Waldenström and Robert Kyle

  13. Treatment of Multiple Myeloma L-sarcolysin (L-phenylalanine mustard) (Melphalan) (Alkeran) Blokhin et al, 1958 Bergsagel et al, 1962 CP1143748-22

  14. Multiple MyelomaSingle (M/P) vs CombinationChemotherapy (CCT) n=4,930 (20 trials) Therapy Response (%) M/P 53 CCT 60 P<0.00001 No difference in survival No subsets with benefit CP1123175-33

  15. Novel Agents • High Dose Therapy with stem cell transplant • Thalidomide • Bortezomib (Velcade) • Lenalidomide (Revlimid)

  16. Multiple Myeloma Novel Agents Pomalidomide (Pomalyst) CC-4047 Carfilzomib (Kyprolis)PR-171

  17. Multiple Myeloma Novel Agents Proteosome inhibitor (oral/IV) MLN-9708 Proteosome inhibitor (oral) NPI-0052 Elotuzumab Bendamustine Histone deacetylase inhibitor Vorinostat (SAHA) Histone deacetylase inhibitor Panobinostat

  18. Multiple Myeloma 1971-2006n=2,981 P<0.001 Survival, med 44.8 mo Proportion surviving Survival, med 29.9 mo Diagnosis after 1996 Diagnosis during/before 1996 Time from diagnosis (months) Kumar et al: Blood 111:2516, 2008 CP1315995-1

  19. Multiple MyelomaMayo Patients 2006-2010 66% P < 0.0001 47% 2001-2005 S. Kumar, 2012

  20. Future Imperfect Isaac Asimov 1964 Predictions Scientific American, March 2014

  21. Pneumococcal Pneumonia1939 • Lobar pneumonia • High fever, cough • Resolution of fever or death • Need more potent Pneumococcal antisera

  22. Fleming and Penicillin • Contaminated Petrie dish byStaphylococcus and fungus • Fleming identified Penicillin • Unable to successfully extract adequate quantities

  23. Discovery of Penicillin “I had noticed the anti-bacterial effect of fungi by chance but Duchesne didso by methodic investigations.” Sir Alexander Fleming Kyle RA and Shampo MA. JAMA 241:1886, 1979.

  24. Discovery of Penicillin Professor Gabriel Roux advised the study of competition of cultures of bacteria and fungi. Duckett S. Lancet 354:2068, 1999.

  25. Discovery of Penicillin 1896 Guinea pigs inoculated with E. coli or S. typhi Saline injection Death Penicillin glaucum Survival Kyle RA and Shampo MA. JAMA 248:847, 1978.

  26. Discovery of Penicillin 1897 “ We hope that the pursuit of these studies on the vital competition for life between fungi and microbes that we have only begun here, and for which we do not pretend to have made more than a small contribution, may result in the discovery of other facts useful and applicable to prophylactic hygiene and therapy.” Ernest Duchesne Duckett S. Lancet 354:2068, 1999.

  27. kyle.robert@mayo.edu

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