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Scottsdale, Arizona

Scottsdale, Arizona. Rochester, Minnesota. Jacksonville, Florida. Rafael Fonseca MD Chair, Department of Medicine Mayo Clinic in AZ Multiple Myeloma: Is FISH passé?. Mayo Clinic College of Medicine Mayo Clinic Comprehensive Cancer Center. Disclosures.

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Scottsdale, Arizona

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  1. Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida Rafael Fonseca MDChair, Department of Medicine Mayo Clinic in AZMultiple Myeloma: Is FISH passé? Mayo Clinic College of Medicine Mayo Clinic Comprehensive Cancer Center

  2. Disclosures • Consulting: AMGEN, Genzyme, BMS, Otsuka, Celgene, Medtronic, Lilly, Millennium, Binding Site, Onyx, Bayer • Speakers Bureaus: None • Research: Cylene, Proteolix • Patent for FISH based prognostication in MM - about $1500 per year • Registered independent • Believe in stem cell transplant • Dislike wasting your time with this slide

  3. Is FISH passé? Rotten FISH Nigiri Toro

  4. Why do risk stratification • Old days • Early use of bortezomib • Overall prognosis • New era • Pt counseling (“chronic disease”) • Post transplant consolidation • Tandem SCT? • Options for low risk cases

  5. Example case • 47 y.o. with new diagnosis IgA lambda MM • Seen for 2nd opinion for SCT • Treated with RVD • Achieved VGPR after 4 cycles • Outside report • FISH – negative (3rd pull, path, flow and …) • No selection • No cIg • Sample is obtained and has t(4;14) & -17p13

  6. IgH Translocations Fonseca et al Blood 100:1417

  7. Molecular Prognostic Model All others including t(11;14) P<0.001 D13 Poor 24.7 mos Intermediate 42.3 mos Good 51.0 mos Survival probability t(4;14) t(14;16) -17p13 Months Fonseca et al Blood 101:4569, 2003

  8. t(11;14) Myeloma

  9. TC Classification Bergsagel P L et al. Blood 2005;106:296-303

  10. GEP signatures Shaughnessy et al, Blood2007, 109(6), 2276-2284

  11. Prognosis by Genomic Complexity Chung T-H, Mulligan G, Fonseca R, Chng WJ (2013) A Novel Measure of Chromosome Instability Can Account for Prognostic Difference in Multiple Myeloma. PLoS ONE 8(6): e66361. doi:10.1371/journal.pone.0066361 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066361

  12. So what is best to identify HR MM?Is there a perfect or best way • All systems work • Not one system will be 100% (so far) • More powerful ones are usually smaller in number • None of genetic systems combine clinical variables which may be just as important • It is important to understand them!

  13. Extramedullary MyelomaGraphical Overview

  14. Truncating Mutation of Cereblon in Drug Resistant patient

  15. MMRC # IIII III IIII Marrow collection; Practicalities Repositioning of needle Swamp analogy Contamination with peripheral blood Sufficient number of cells Purity post sort Need for viable and CD138+ cells CD138 Beads

  16. PFS by Cytogenetic Category; TD 2 - 35 Day courses of consolidation Cavo M et al. Blood 2012;120:9-19

  17. PFS by Cytogenetic Category; VTD 2 - 35 Day courses of consolidation Cavo M et al. Blood 2012;120:9-19

  18. Landmark Start of Consolidation t(4;14) and no -17p13 All TD VTD Cavo M et al. Blood 2012;120:9-19

  19. Effects of -17 by Treatment Arm Bortezomib Arm B (Blue-Black) Neben K et al. Blood 2012;119:940-948

  20. Studied 8 patients with 17p deletions at RR 7 did not have deletion at diagnosis FISH (MGUS n=184, SMM n=116, relapsed MM n=62 and PCL n=26) aCGH (newly diagnosed MM n=224, relapsed MM n=158 and HMCLs n=48) p 53 mutational status was evaluated in relapsed MM (n=84) and HMCLs (n=48) *Tiedemann et al. Leukemia. 2008; 22, 1044-1052 Fonseca. Manuscript in preparation

  21. Conclusion

  22. Conclusion • FISH (cons) • Imperfect (GEP more powerful) • Technically specialized • FISH (pros) • Very, very practical • Global • Sufficient

  23. Is FISH passé? Rotten FISH Nigiri Toro Solid Salmon

  24. Is FISH passé?

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