1. Should complete remission, however strictly defined, be the goal for everyone? YES! New York, October 23, 2014 Ola Landgren, M.D., Ph.D. Chief, Myeloma Service Memorial Sloan-Kettering Cancer Center, New York www.MSKCC.org

3. Alternative: be lazy, take it easy

4. 123456 “YES ARGUMENTS”

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6. Respect your elders!

7. Kapoor et al. J Clin Oncol 2013 Importance of good clinical response

8. 123456 “YES ARGUMENTS”

10. Newer myeloma drugs provide better clinical response Kumar Cancer Treatment Reviews 2010; Korde et al. ASH 2013 CRd

11. 123456 “YES ARGUMENTS”

13. Kapoor et al. J Clin Oncol 2013 Clinical response to therapy impacts progression-free survival

14. Clinical response to therapy impacts overall survival Kapoor et al. J Clin Oncol 2013

15. 123456 “YES ARGUMENTS”

16. Quality matters

17. At diagnosis Partial response (50% reduction in M protein) Near complete remission (immunofixation pos only) Complete remission (immunofixation neg) 1 × 10 12 Number of myeloma cells 1 × 10 8 Why stop at CR, when we are not yet done? Cure MRD- Non-quantitative ASO-PCR of bone marrow Quantitative ASO-PCR of bone marrow High quality flow cytometry of bone marrow Deep sequencing of bone marrow 1 × 10 4 1 × 10 6 MRD+ 0

18. Kapoor et al. J Clin Oncol 2013 Clinical response to therapy impacts progression-free survival

19. Clinical response to therapy impacts overall survival Kapoor et al. J Clin Oncol 2013

20. Among CR patients, flow cytometry MRD- impacts survival Rawstron et al. J Clin Oncol 2013

21. Myeloma genetics and MRD status: impact on overall survival Hyperdiploidy, t(11;14), or t(6;14) Gain(1q), del(1p32), t(4;14), t(14;20), t(14;16), or del(17p)

22. 123456 “YES ARGUMENTS”

23. Myeloma is NOT a Polaroid!

25. Sustained stringent clinical response to therapy impacts overall survival Kapoor et al. J Clin Oncol 2013

26. 123456 “YES ARGUMENTS”

28. There is already a literature: we are already doing it! Number of published myeloma MRD studies associated with clinical outcomes Landgren et al. unpublished data

29. Summary and Conclusions Deeper responses in more patients Deeper responses = better survival Deeper is better, MRD next step forward

31. Thank you for your attention! Ola Landgren, M.D, Ph.D. Chief, Myeloma Service Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065, USA Email: landgrec@mskcc.orglandgrec@mskcc.org Phone: 212-639-5126