Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 1

Is Multiple Myeloma curable in 2012? No-Prolonged control does not equal cure

S. Vincent Rajkumar, MDj ,Mayo Clinic

Mayo Clinic College of MedicineMayo Clinic Comprehensive Cancer Center

Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida

Myeloma Risk-Stratification

High-Risk Intermediate-Risk Standard-Risk

msmart.org

FISH Del 17p t(14;16) t(14;20)

GEP defined high-risk

All others including: Hyperdiploid t(11;14) t(6;14)

FISH t(4;14)

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 2

I. Why does this debate matter?

© Remstein E, Jevremovic D. Rajkumar SV. 2010

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 3

II. What is Cure in Cancer?

Molecular Cure

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 4

Clinical Cure

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 5

ALL

Pui et al. N Engl J Med 2006; 354:166-178

APLOverall Survival by age

Park J H et al. Blood 2011;118:1248-1254

©2011 by American Society of Hematology

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 6

Overall survival of Large Cell Lymphoma in patients treated with CHOP and R-CHOP.

Coiffier B et al. Blood 2010;116:2040-2045

©2010 by American Society of Hematology

Survival in Myeloma without SCT and prior to new agents

MTCG. J Clin Oncol 1998; 16:3832

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 7

Survival in Myeloma in Transplant Eligible PatientsEarly or Late SCT: SWOG S9321 Trial

Barlogie JCO 2006;24:929-936

TT3 for MM: 2003-33 and 2006-66 trials.

Nair B et al. Blood 2010;115:4168-4173©2010 by American Society of Hematology

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 8

TT3 2003-33 and 2006-66 trials GEP–defined low risk in CR

228/480 (48%)

Nair B et al. Blood 2010;115:4168-4173©2010 by American Society of Hematology

Kaplan-Meier plots of (A) overall and (B) event-free survival outcomes.

Barlogie B et al. JCO 2010;28:1209-1214

©2010 by American Society of Clinical Oncology

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 9

Operational Cure

II. Is “cure” or “operational cure” needed?

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 10

Transplant Eligible

Standard Risk High Risk Intermediate Risk

Autologous stem cell transplant

Rd x 4

Collect Stem Cells

VRd X 4

Autologous stem cell transplant

VCD x 4

Autologous stem cell transplant

VDT-PACE

ASCT x 2

Second ASCT only if not in VGPR after first

Continue Rd

VCd x 1 yearVRd x 1-3 years

Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110v7 Revised and updated: Jan 2011

VRD x 3 years

TT3 for MM: 2003-33 and 2006-66 trials.

Nair B et al. Blood 2010;115:4168-4173©2010 by American Society of Hematology

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 11

(n=82)

(n=41)

Outcome of New MM treated at Mayo Clinic

Kumar S. Cancer Aug 2011

Updated Outcome of New MM treated at Mayo ClinicTransplant eligible

N=2726-yr OS: 71%SCT 140 onlySCT 140 only

Kumar S. 2011

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 12

CR is critical in patients with high-risk myeloma

Low-Risk MM (87%) High-Risk MM (13%)

Copyright ©2007 American Association for Cancer Research

Haessler, J. et al. Clin Cancer Res 2007;13:7073-7079

CML

Gugliotta G et al. Blood 2011;117:5591-5599

©2011 by American Society of Hematology

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 13

III. What is clinical benefit?

Rajkumar SV Kyle RA and. Cecil Textbook of Medicine, 23nd Edition, 2007

Kyle RA and Rajkumar SV. N Engl J Med 2004;351:1860-73

Treatment of Myeloma: Combination or Sequential TherapyS. Vincent Rajkumar, MD

Please review the accompanying Treatment of Myeloma: Cure vs Control Symposium Program Handout for important information related to this presentation. This material serves as an educational resource only. 14

Historical Lessons

• MP

• CHOP

• SCT for breast cancer

• HRT

• Etc, etc

Overall Survival Improved PRO

One

Phase III

Change in

Two

Phase IIIsClinical Benefit Safety

Rajkumar SV. 2011

Change in

Clinical Practice