Presentation on the Basics of Writing. Writing a Paragraph
MULTIPLE MYELOMA : RAVI VIJ
1. Induction Therapy For Multiple
Myeloma:
Two vs Three Drug Regimen and Role of Risk
Stratification
Ravi Vij MD
Associate Professor
Section of BMT and Leukemia
Washington University School of Medicine
2. Trends in Overall Survival of MM
Overall survival 1971–2006
Diagnosis period Median OS
1996–2006 45 months
1971–1996 30 months
(P<0.001)
Kumar SK, et al. Blood. 2008;111:2516-2520.
Time from diagnosis (Months)
Survival
0
0.2
0.4
0.6
0.8
1.0
0 20 40 60 80 100 120 140
2001–2006
1995–2000
2001–2006
1989–1994
1983–1988
1977–1982
1971–1976
OS, overall survival.
2
M
3. CR and MM
• Is CR an adequate surrogate for OS?
• Are all CRs as durable?
• Should we strive for CR pre-transplant?
• What is the role of HDCT for patients in CR pre-transplant?
4. CR associated with OS prolongation in post-
induction and post-transplant settings1-3
1. Lahuerta et al. J Clin Oncol. 2008;26(3):5775-5782. 2. Alexanian et al. Bone Marrow Transplant. 2001;27:1037-1043. 3. Wang, et al. Bone Marrow Transplant.
2010;45(3):498-504.
Survival by response for 291 patients with MM (age <70 y) who received chemotherapy alone (left)
and 375 who proceeded to ASCT (right) (CR vs PR or NR P<0.01)
Chemotherapy Alone Chemotherapy and ASCT
4
5. > 65 yrs
> 75 yrs
Importance of CR in Elderly MM
Gay F et al. Blood. 2011;117(11):3025-3031)
6. Approach to Treatment of MM
Clearly not a transplant candidate
based on age, performance status
and comorbidity
Conventional Therapy
Potential transplant
candidate
Non-alkylator based
induction x 4 cycles
Stem cell harvest
7. Bortezomib-Based Induction Prior to
SCT
Trial Regimen N
CR+VGPR Post-
Induction (%)
CR+VGPR Post-ASCT
(%) PFS P Value
Cavo et al, 2010
VTD
vs
TD
236
238
62*
28
82*
64
68% at 3 yr
56% at 3 yr
.0057
Moreau et al, 2011
IFM 2007/02
VD
vs
vTD
99
100
36
49‡
58
74§
Median 30
months
Median 26 mo
.22
*P <.001; †P =.001; ‡P =.05; §P =.02
GMMG= German Multiple Myeloma Group; SCT = stem cell transplant; CR = complete response; VGPR = very good
partial response; PAD = bortezomib (V)/AD; T = thalidomide; VAD = vincristine, doxorubicin (A), dexamethasone (D); vTD
= reduced-dose bortezomib.
Cavo M, et al. Lancet. 2010;376:2075-2085. Harousseau JL, et al. J Clin Oncol. 2010;28:4621-4629. Sonneveld P, et al. ASH
Annual Meeting Abstracts. 2010;116(21):40. http://web.educationalconcepts.net/Newsletter/MMY015AE1/MMY015AE1.pdf.
Accessed July 17, 2012. Moreau P, et al. Blood. 2011;118: 5752-5758.
8. Fayers PM et alBlood.2011;118(5):1239-1247
MPT vs MP in Elderly MM
10. Palumbo et al. N Engl J Med 2012;366:1759-69.
MPR vs MP in Elderly MM
11. Study Regimen N ORR CR/nCR Outcomes
VISTA
San Miguel et al.
Mateos et al.
Phase III
VMP
MP
344
338
71%
35%
33%
4%
5 yr OS: 46%
5 yr OS: 34.4%
UPFRONT
Niesvizky et al.
Phase III
VMP/Vel
VTD/Vel
VD/Vel
300
73%
79%
71%
31%
36%
34%
ORR: overall response rate; CR: complete response; nCR: near complete response; OS: overall survival; TTP: time to progression; PFS: progression free survival; VMP: Bortezomib-melphalan-dexamethasone; MP: Melphalan-
Prednisone; VTP: Bortezomib-thalidomide-dexamethasone; VTD: bortezomib-thalidomide-dexamethasone; VD: bortezomib-dexamethasone; VMPT-VT: bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance
Bortezomib in Transplant Ineligible MM
13. MM-020: Len + Low-dose Dex vs MPT in
Previously Untreated MM
Protocol CC-5013-MM-020/IFM 07-01. 2007; data on file, Celgene Corporation
Inclusion criteria
•Previously
untreated MM
•Age 65 years or
not a candidate
for transplantation
•No neuropathy of
grade > 2
•CICr > 30 ml/min
• Lenalidomide 25 mg/day, days 1–21, every 28 days
• Dexamethasone* 40 mg/day, days 1, 8, 15, 22, every
28 days
Until PD
• Lenalidomide 25 mg/day, days 1–21, every 28 days
• Dexamethasone* 40 mg/day, days 1, 8, 15, 22, every
28 days
18 four-
week
cycles or
until PD
N = 1,590
Centres in EU,
Switzerland, USA and
Canada
*In patients older than 75 years
• Dexamethasone 20 mg/day
• Thalidomide 100 mg/day
• Melphalan 20 mg/kg/day
• Melphalan 0.25 mg/kg/day, days 1–4, every 42 days
• Prednisone 2.0 mg/kg/day, days 1–4, every 42 days
• Thalidomide* 200 mg/day, days 1–42, every 42 days
12 six-
week
cycles or
until PD
16. Conclusions
• Three drug induction regimen are associated with higher
CR rates compared to two drug regimen.
• In the transplant eligible population prospective trials have
shown a higher CR rate and PFS for two drug regimen.
Follow-up is too short for analyses of OS.
• In the transplant ineligible population three drug regimes
of thalidomide and bortezomib have a OS advantage
compared with MP. Whether non-melphalan containing
two drug regime may be equivalent is the subject of
ongoing trials.
• We have entered an era of risk stratification for deciding
therapy. However no consensus has emerged on treatment
paradigms.
Notes de l'éditeur
Trends in Overall Survival of MMKumar et al studied survival in 387 patients who were treated at the Mayo Clinic from 1971–2006 and experienced a first relapse after ASCTPatients were divided into 2 cohorts, those with a relapse date on or before December 31, 2000 and those with a later relapse date Median overall survival (OS) was longer for patients who relapsed after 2000 compared with those who relapsed prior to this date (23.9 vs 11.8 months)Improved outcome of patients with MM has been observed in recent years, both in the relapsed setting as well as at diagnosisReferenceKumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and theimpact of novel therapies. Blood. 2008;111(5):2516-2520.
CR associated with OS prolongation in post-induction and post-transplant settingsAssessing the prognostic impact of achieving CR has been difficultbecause of the use of different definitions of CR.1 [Harousseau/p3139/c2/para3/lines1-3]Although not all studies show a correlation between CR and OS in MM, CR generally indicates patients who are likely to live longer.2 [Wang/p500/fig1]Many studies have demonstrated that CR is usually associated with longer overall survival.1[Harousseau/p3140/c2/para1/lines1-9]These findings have been demonstrated in both the postinduction and posttransplant settings.3[Lahuerta/p5778/table3]1. Harousseau J-L et al. Blood. 2009;114(15):3139-3146. 2. Wang M et al. Bone Marrow Transplant. 2010;45(3):498-504.3. Lahuerta JJ et al. J Clin Oncol. 2008;26(35):5775-5782.