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(No Transcript)
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• ????????(MM)?????????????????????????????????????
  ??????????????????????????????????????????????
• ??1844 Samuel Solley????
• 1850 William Macintype ?Henry
• Bence Jones???-?????
• 1873 J.von Rustizky??MM??
• 1935 ????????? M?

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MM ?????

• ??? ???????1,?????10?
• ???? 4/10?,?? 10/10???
• ??2.53.0/10?
• ??1.0/10???
• ???????,???1.0-2.0/10???
• ???????,??????????
• ???? 6570?,???? 68?
• ???? 5565?,???? 57?
• ??????????2-2.51

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???????????(??????)
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• ? ???/????M??
• ? ???????????????
• ???10 ???
• ? ?????????

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• ? IF????/????M??
• ? ?????????10,??????
• ? ROTI
• ? ???????????????????????????

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Initial Diagnostic Evaluation

• History and physical examination
• Blood workup
• CBC with differential and platelet counts
• BUN, creatinine
• Electrolytes, calcium, albumin, LDH
• Serum quantitative immunoglobulins
• Serum protein electrophoresis and immunofixation
• ß2-microglobulin
• Serum free light chain assay

• Urine
• 24-hr protein
• Protein electrophoresis
• Immunofixation electrophoresis
• Other
• Skeletal survey
• Unilateral bone marrow aspirate and biopsy
  evaluation with immunohistochemistry or flow
  cytometry, cytogenetics, and FISH
• MRI as indicated

NCCN Practice Guidelines. V.1.2011.
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IMWG Classification of Active MM

• High Risk (25)
• FISH
• Del 17p
• t(414)
• t(1416)
• Cytogenetic deletion 13q

• Standard Risk (75)
• All others, including
• Hyperdiploidy
• t(1114)
• t(614)

Patients with t(414), ß2-M lt 4 mg/L and Hb 10
g/dL may have intermediate-risk disease.
Dispenzieri A, et al. Mayo Clin Proc.
200782323-341. Fonseca R, et al. Leukemia.
2009232210-2221. Munshi N, et al. Blood.
20111174696-4700
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?????????

• IgG?
• 4050,?????? M????,?????????,????,????????,
  ????????????
• IgA?
• 1520??????????????????,???????,???IgG??
• ???
• 20,??????????????,??????,???????,???IgG??IgA
  ??

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• IgD?
• ???13,?????5-10???????????,?50???????,??
  ?????,??????,???????????,????????,?????????????,??
  ????,????,?????
• IgM?
• ????????
• ?????????
• 0.52.5,????????????
• IgE ?
• ??

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Durie ?Salmon????(1975) ?? ????
???? I? lt0.6x1012/m2 1)
HBgt100g/dl2)?????
3)X??????
4)IgGlt50g/LIgAlt30g/L

???lt4g/24h II? 0.6-1.2x1012/m2
? I??III III? gt 1.2x1012/m2 1)
HBlt85g/L 2)??gt12mg/dl
3)????????
4) IgGgt 70g/LIgA gt 50g/L
????gt
12g/24h A???lt2.0mg/dl B??? gt 2.0mg/dl
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??????(ISS)
?? b2M ??? N ????
I lt3.5 3.5 2401 62 mos.
II lt3.5 3.5 -lt5.5 lt3.5 ? 3278 44
III 5.5 2770 29
??????????? 11,171???, ???????,??
b2?????????????.
Greipp, PR et al. J. Clin. Oncol. 233412, 2005.
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????????

• ??????????? (P lt 0.0001)
• ?Durie-Salmon????,????????
• ????????????

Greipp, PR et al. J. Clin. Oncol. 233412, 2005.
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IMF ????????ß2m???

• ?13q- t (414) 17p??
• ??ß2M lt 4

IFM ?? 513 ??

• t (414) ? 17p??
• ??ß2M gt 4

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????
Herve Avet Loiseau, et al. Blood. 2007.
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(No Transcript)
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?????????????

• Class I ?????
• Class II ??????
• ????? ???????????
• ?????? ????

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??????????????
?? ?? ?? CR/nCR CRPR ??? ?? ????
Rajkumar 100 Dex 0 50 Yes JCO 2006
Goldschmidt 203 VAD 3 63 Yes ASH 2005
Rifkin 97 DVd 3 43 Yes Cancer 2006
IFM90 100 VMCP 5 52 Yes/No NEJM 1996
Palumbo 126 MP 7 48 No Lancet 2006
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????OS???? vs MP??
27 ????? 6633???
0
1
2
3
4
5
6
100
90
80
MP VBMCP VMCP VBAP ABCM MOCCA
70
60
50
????????
40
24.4
30
19.4
1.4 SD 1.4 (log-rank 2P gt .1 NS)
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23.0
18.0
10
0
6 ?
1
2
3
4
5
Myeloma Trialists' Collaborative Group. J Clin
Oncol. 199816123832
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MP??????????
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ASCT????????

• ????
• IFM?????? N200, ??7?
• ASCT
  CT
• CR 38
  14
• EFS 16
  8
• OS 43
  25
• ??????????7590,
• CR 2060

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ASCT vs CT in MM
Attal M, et al. N Engl J Med. 199633591-97.
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ASCT????MM?CR???
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?????ASCT??MM??
(N Engl J Med 20033492495-502)
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??????
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???? ??????(?????) ?????(???)
????? ????? ??? ?????

• ???????????????????
• ????????????12 -18??

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• ????(????),??????????
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• ??????????????????????????????????????
• ??????
• ???????????????,???????18??

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?????????????

• Class I ?????
• Class II ??????
• ????? ??????? ? ???
• ?????? ????

• Class III ??????
• Class IV ???????

MM?????????
????????????CR??????
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???????????
???? ???? ???? (???)
(??)
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?????????????R/RMM
Study Regimen No. of Pts ORR CR (No. of Pts)
Singhal, 1999 Thalidomide 200-800 mg/day 84 32 2
Barlogie, 2001 Thalidomide 200-800 mg/day 169 37 3
Kumar, 2003 Thalidomide 200-800 mg/day 32 31 0
Richardson, 2004 Thalidomide 200-600 mg/day 30 43 0
Dimopoulos, 2001 Thalidomide 200-400 mg Dexamethasone 20 mg 44 55 0
Palumbo, 2001 Thalidomide 100 mg Dexamethasone 40 mg 77 66 2
Dimopoulos, 2004 Thalidomide/Dexamethasone/ Cyclophosphamide 53 60 3
Garcia-Sanz, 2004 Thalidomide/Dexamethasone/ Cyclophosphamide 49 68 5
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????????MM

• MDACC MAYO ECOG
• ?? TD DT TD
  D
• ??? 130 50 103
  107
• PR() 69 64
  69 51
• DVT 24 5
  18 3

Plt0.05, ????????
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MP vs. MPT ??????MM????
?? N PFS(?) P? OS(?) P?
MP 191 17.21.5 lt0.0001 30.35.8 0.0008
MPT 124 29.53.6 lt0.0001 gt56 0.0008
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???????????????
?? ??? ?? CR/nCR CRPR ????
Rajkumar 99 ThalDex 4 63 JCO 2006
Rajkumar 34 LenalDex 38 91 Blood 2005
Niesvizky 35 LenalDexClar 36 86 ASH 2005
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???????????
NFkB
PS-341
IkB
Ubiquitin
Proteosome
VCAM-1
VEGF
IL-6
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????????R/RMM
???? ?? ORR CR/ nCR OS (Ms) TTP (Ms) DOR (Ms)
SUMMIT, 2003, 2006 193 28 10 17 7 12.7
CREST, 2004 53 38 4 Not Reached 11 13.7
CREST, 2004 53 30 11 26.7 7 9.5
Richardson. N Engl J Med. 20032482609
Richardson. Cancer. 20061061316 Jagannath. Br
J Haematol. 2004127165.
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????????????CR?
?? N ?? CR/nCR CRPR ??? ?? ????
Jagannath 49 Bort /- Dex 18 88 Yes ASH 2006
Harousseau 48 Bort Dex 21 67 Yes Hematol 2006
Orlowski 29 Bort/PLD 28 80 Yes ASH 2006
Oakervee 21 PAD 29 95 Yes BrJH 2005
Jakubowiak 28 Bort/PLD/ Dex 32 89 Yes ASH 2006
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???????????
?? ?? ?? CR/nCR CRPR ????
IFM90 100 Autograft x 1 38 81 NEJM 1996
Child 200 Autograft x 1 44 86 NEJM 2003
IFM94 200 Autograft x 1 42 84 NEJM 2003
IFM94 200 Autograft x 2 50 88 NEJM 2003
Oakervee 21 PAD/ Autograft x 1 57 95 BrJH 2005
Harousseau 42 Bort/Dex/ Autograft x 1 54 90 ASCO 2005
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MM??????

• ????
• Bort Dex, PAD
• Len Dex
• TD, VTD
• ????CR
• SCT ?????????

• ????
• MPT
• MPV
• MPR
• ????CR

?Lenalidomide??????????
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(No Transcript)
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• ???????110-120g/L????????????

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• ??????MM??????
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• ??1030 Gy
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??MM???????
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????

• ??
• VAD or VDD
• ????????
• MP or MPT

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• ???? ????
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• ????/????/????
• MPR
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