Education
1989 : Medical Doctor Padjajaran University
1993 : MSc Research Methodology University of Aberdeen, UK
1999 : Internist Padjajaran University
2006 : Hematology-Medical Oncology Padjajaran University
Current Concept and Treatment of Multiple Myeloma
Pandji Irani Fianza
Chromosome 13 abnormalities
Monosomy
Deletion 13
13q translocations
17p deletions
Hyperdiploid
Stages I, II, and III of the Durie-Salmon staging system can be divided into
A or B depending on serum creatinine:
A: serum creatinine < 2 mg/dL (< 177 μmol/L)
B: serum creatinine > 2 mg/dL (> 177 μmol/L)
International Staging System
* There are two categories for stage II: serum β2-microglobulin < 3.5 mg/L
but serum albumin < 3.5 g/dL; or serum β2-microglobulin 3.5 to < 5.5 mg/L
irrespective of the serum albumin level.
I 69 47
II 50 37
III 33 24
Efficacy Toxicity
VGPR 73.7%
P < .001 P < .0001 67%
64%
18.6%
P < .001 P = .03
61% 62.3% 66% 32% 60%
CR/nCR 54.3% 54%
P = .87 P < .001 P < .0001 23%
50% P < .001 44% 31% 21.4%
44.4% P = .004 19.3% 42% 43.2%
P = .002 41.7%
37.7% 37.2% 37% 36% 35%
34.7% 55.1%
27.2% 28% 55% TD
40% 27.5%
22.9% 18.8% 21%
35.0% 18% 32% 31% 40.9% CR/nCR
12.6% 15.1% 34% 17%
17.1% 31% 41% 43%
30%
16% 15% CR/nCR
14.8% 8.7% 18.4% 15% 16% 11% 33%
6.4% 3% 2% 14% 12% 11% 5% 10.4%
0%
TD VAD TD VAD VD VAD VD VAD TAD VAD TAD VAD PAD VAD PAD VAD CTD CVAD CTD CVAD VTD TD VTD TD CyBorD RVD
Pre-HDT Post-HDT Pre-HDT Post-HDT Pre-HDT Post-HDT Pre-HDT Post-HDT Pre-HDT Post-HDT Pre-HDT Post-HDT
Macro IFM2005-01 HOVON 50 HOVON 65 MRC IX GIMEMA
Macro M, et al. Blood. 2006;108:57-62. Harousseau JL, et al. J Clin Oncol. 2010;28:4621-4629. Lokhorst
HM, et al. Blood. 2010;115:1113-1120. Sonneveld P, et al. IMW 2010. Abstract 40. Cavo M, et al. Lancet.
2010;376:2075-2085. Reeder CB, et al. Blood. 2009;114: abstract 616. Richardson PG, et al. Blood.
2009;114: abstract 1218. Kumar SK, et al. Leukemia. 2010;24:1352-1356.
Bortezomib
• A proteasome inhibitor
• Has shown good efficacy as a single agent and in
combination in patients
– with relapsed multiple myeloma
– as initial treatment, including prior to autologous stem
cell transplantation
• Has been studied as monotherapy and in combination
with standard treatments, such as dexamethasone,
chemotherapy, and with newer agents such as the
IMiDs, thalidomide and lenalidomide
• Is well-tolerated, including in combination
Bortezomib: a potent first-in-class
proteasome inhibitor
Dipeptidyl boronic acid Cross-section of b-ring
derivative
b1 Post- b2
Tryptic
glutamyl
site
site
O OH b7 b3
H
N N B
N OH Bortezomib
H b6 b4
O Chymo-
N tryptic
b5 site
Janssen-Cilag 2003
Single-agent bortezomib active in
newly diagnosed MM
Richardson et al.
RR (CR+PR), n=28 45% (67% including MR)
Jagannath et al.*
RR (CR+nCR+PR) 41% (after 2 cycles), 11% CR+nCR
(23 pts evaluable) 85% (after addition of Dex),
20% CR+nCR
N=511
TNT
PFS
OS after
OS Relapse
Conclusion
Bortezomib and thalidomide maintenance significantly improved
OS in multiple myeloma patients
Suvannasankha
+ steroids II 30 60% 6%
(25621)
+ pegylated
liposomal doxorubicin I 42 73% 36% Orlowski2
CR+PR 34%
CR+PR 45%
80 P<0.0001
60
45
40 34
26
32
21
20 13
23 0.5 nCR
6 7
13
6 2 6
0
Bortezomib Dex Bortezomib Dex
1 prior line of therapy >1 prior line of therapy