1. Education
Clinical Care
Research
Multiple Myeloma: Risk Stratified Treatment
Strategies
A/Prof Chng Wee Joo
Head, Haematologic Malignancies
Department of Haematology-Oncology
National Cancer Institute of Singapore
National University Health System
Deputy Director and Senior Principle
Investigator
Cancer Science Institute, Singapore
National University of Singapore

2. International Staging System
Greipp et al JCO 2005;23:3142

3. Genetic Abnormalities Detected by
FISH
Abnormalities Frequencies Prognosis
t(4;14) 10-15% Poor
t(11;14) 15-20% Neutral
t(14;16) 3-5% Poor
1q21 Gain 30-35% Poor
13q14 del 45-50% Neutral
17p13 del 5-10% Poor

4. Summary of Prognostic Factors
Pre-treatment Post-treatment
Host Age
Albumin
Tumor Burden MRI/PET-CT
Durie-Salmon
Beta-2 microglobulin
MRI/PET-CT
Tumor Biology PCLI
Genetics
Response

5. Prognostic impact of t(4;14)/del(17p) with ISS
4-year
Deaths/N estimate
a ISS I or ISS II and Normal FISH 193/610 76% (72,79)
b ISS I and Abnormal FISH/ISS III and Normal FISH 140/252 52% (45,58)
c ISS II or ISS III and Abnormal FISH 146/196 32% (26,39)
Avet-loiseau et al. ASH 2009

7. JCO 2012 epub

8. Can novel agents modulate risk?

13. A1 A2 B1 B2
Induction
Consolidation
HDT with Mel200 & ASCT
VAD x 4 VAD x 4 Vel-Dex x 4 Vel-Dex x 4
DCEP x 2 DCEP x 2
JCO 2010; 28; 4630-4634

14. t(4;14) with Velcade®
treatment VAD Vel/Dex pvalue
(logrank)
Patients 98 106
0.0006Relapses 82 43
Median EFS
(years) [IC 95%]
1.36
[1.08 ;
1.56]
2.32
[1.49 ;
2.95]
p=.0006
Vel/Dex
VADp=.0006
Vel/Dex
VAD
p=.0004
treatment VAD Vel/Dex pvalue
(logrank)
Patients 106 107
0.0004Deaths 70 20
Median OS
(years) [IC 95%]
2.87
[1.76 ;
3.48]
---*
[3.60 ; --
-*]
EFS OS

15. t(4;14) with Velcade®
t(4 ;14) neg pos pvalue
(logrank)
Patients 396 106
0.0178Relapses 141 43
Median EFS
(years) [IC 95%]
2.90
[2.74 ;
3.53]
2.32
[1.49 ;
2.95]
p<.02
t(4;14) pos
t(4;14) neg
t(4;14) neg
t(4;14) pos
p=.002
t(4 ;14) neg pos pvalue
(logrank)
Patients 400 107
0.0020Deaths 38 20
Median OS
(years) [IC 95%]
---*
[---* ; ---*]
---*
[3.60 ; ---
*]
EFS
OS

16. Del(17p) with Velcade®
treatment VAD Vel/Dex pvalue
(logrank)
Patients 101 50
0.3156Relapses 82 30
Median EFS
(years) [IC 95%]
1.47
[1.17 ;
1.83]
1.17
[0.72 ;
2.01]
Vel/Dex VAD
p=.32
Vel/Dex
VAD
p=.49
treatment VAD Vel/Dex pvalue
(logrank)
Patients 115 51
0.4857Deaths 70 15
Median OS
(years) [IC 95%]
2.40
[1.83 ;
3.66]
4.07
[3.10 ; --
-*]

17. Del(17p) with Velcade®
Del(17p) > 60% pvalue
(logrank)
Patients 475 50
< 0.0001Relapses 166 30
Median EFS
(years) [IC 95%]
2.95
[2.75 ;
3.71]
1.17
[0.72 ;
2.01]
p<.0001 Del(17p) pos
No del(17p)
No del(17p)
Del(17p) pos
p<.0001
Del(17p) > 60% pvalue
(logrank)
Patients 480 51
< 0.0001Deaths 48 15
Median OS
(years) [IC 95%]
---*
[---* ; ---*]
4.07
[3.10 ; --
-*]
EFS
OS

18. Lancet 2010; 376: 2075-2085

22. Shaughnesy et al. Br J Haematol 2009; 147:347-351

24. Risk Stratification

25. What have we learn
• Velcade especially benefit t(4;14) patients
• Inclusion of Velcade (and hence prolonged use) in
different phases of treatment is important in high-risk
disease
• The use of double autologous transplant seem to
also be an important factor.
• Revlimid seem to have a more moderate and less
consistent effect on high-risk disease
• Thalidomide maintenance contra-indicated in 17p13
deletion

26. How do I apply Risk Stratification in
Clinic for transplant eligible patients?
• Induction
– Velcade triplet for everyone if can afford
– If cannot afford
• Velcade triplet for intermediate and high-risk
disease
• CTD for standard and low-risk disease. If not
VGPR by 4 cycles, to then change to velcade
triplet

27. How do I apply Risk Stratification in
Clinic for transplant eligible patients?
• ASCT Consolidation
– Double (Mel200) autologous SCT for
intermediate and high-risk disease
– Single transplant (Mel200) for others
– If did not have Velcade at induction,
consider incorporating velcade to Mel200
conditioning

28. • Post-ASCT Consolidation
– If low or standard-risk, no consolidation if achieve
VGPR
– If intermediate or high-risk, 2 cycle of Velcade
triplet consolidation regardless of response
• Maintenance
– If low-risk, no maintenance if achieve VGPR
– If standard-risk, Rev maintenance
– If intermediate or high-risk, Velcade maintenance
How do I apply Risk Stratification in
Clinic for transplant eligible patients?

29. Risk Stratification - Questions

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