should complete remission, however strictly defined, be the goal for everyone? yes! new york,...

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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

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Page 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

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

Page 2: 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
Page 3: 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

Alternative: be lazy, take it easy

Page 4: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 5: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 6: 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

Respect your elders!

Page 7: 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

Kapoor et al. J Clin Oncol 2013

Importance of good clinical response

Page 8: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 9: 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
Page 10: 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

Newer myeloma drugs provide better clinical response

Kumar Cancer Treatment Reviews 2010; Korde et al. ASH 2013

CRd

Page 11: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 12: 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
Page 13: 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

Kapoor et al. J Clin Oncol 2013

Clinical response to therapy impacts progression-free survival

Page 14: 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

Clinical response to therapy impacts overall survival

Kapoor et al. J Clin Oncol 2013

Page 15: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 16: 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

Quality matters

Page 17: 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

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

Page 18: 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

Kapoor et al. J Clin Oncol 2013

Clinical response to therapy impacts progression-free survival

Page 19: 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

Clinical response to therapy impacts overall survival

Kapoor et al. J Clin Oncol 2013

Page 20: 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

Among CR patients, flow cytometry MRD- impacts survival

Rawstron et al. J Clin Oncol 2013

Page 21: 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

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)

Page 22: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 23: 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

Myeloma is NOT a Polaroid!

Page 25: 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

Sustained stringent clinical response to therapy impacts overall survival

Kapoor et al. J Clin Oncol 2013

Page 26: 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

1 2 3 4 5 6“YES ARGUMENTS”

Page 27: 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
Page 28: 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

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

Page 29: 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

Summary and Conclusions

• Deeper responses in more patients

• Deeper responses = better survival

• Deeper is better, MRD next step forward

Page 30: 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
Page 31: 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

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