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Should complete remission, however strictly defined, be the goal for everyone? YES!
New York, October 23, 2014Ola Landgren, M.D., Ph.D.Chief, Myeloma ServiceMemorial Sloan-Kettering Cancer Center, New Yorkwww.MSKCC.org
Alternative: be lazy, take it easy
1 2 3 4 5 6“YES ARGUMENTS”
1 2 3 4 5 6“YES ARGUMENTS”
Respect your elders!
Kapoor et al. J Clin Oncol 2013
Importance of good clinical response
1 2 3 4 5 6“YES ARGUMENTS”
Newer myeloma drugs provide better clinical response
Kumar Cancer Treatment Reviews 2010; Korde et al. ASH 2013
CRd
1 2 3 4 5 6“YES ARGUMENTS”
Kapoor et al. J Clin Oncol 2013
Clinical response to therapy impacts progression-free survival
Clinical response to therapy impacts overall survival
Kapoor et al. J Clin Oncol 2013
1 2 3 4 5 6“YES ARGUMENTS”
Quality matters
At diagnosis
Partial response (50% reduction in M protein)
Near complete remission (immunofixation pos only)
Complete remission (immunofixation neg)
1 × 1012
Num
ber o
f mye
lom
a ce
lls
1 × 108
Why stop at CR, when we are not yet done?
CureMRD-
Non-quantitative ASO-PCR of bone marrow
Quantitative ASO-PCR of bone marrow High quality flow cytometry of bone marrowDeep sequencing of bone marrow1 × 104
1 × 106
MRD+
0
Kapoor et al. J Clin Oncol 2013
Clinical response to therapy impacts progression-free survival
Clinical response to therapy impacts overall survival
Kapoor et al. J Clin Oncol 2013
Among CR patients, flow cytometry MRD- impacts survival
Rawstron et al. J Clin Oncol 2013
Rawstron et al. J Clin Oncol 2013
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)
1 2 3 4 5 6“YES ARGUMENTS”
Myeloma is NOT a Polaroid!
Sustained stringent clinical response to therapy impacts overall survival
Kapoor et al. J Clin Oncol 2013
1 2 3 4 5 6“YES ARGUMENTS”
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 unpublished data
1
81
1
3
PFS
sCR
Flow
NGS
PET CT
ASO PCR
1
3
1
1
OS
Summary and Conclusions
• Deeper responses in more patients
• Deeper responses = better survival
• Deeper is better, MRD next step forward
Thank you for your attention!
Ola Landgren, M.D, Ph.D.Chief, Myeloma Service
Memorial Sloan-Kettering Cancer Center1275 York Avenue, New York, NY 10065, USA
Email: [email protected] Phone: 212-639-5126