optimal use of transplant for myeloma early-late-nonablative koen van besien, md, phd weill cornell...
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Optimal Use of Transplant for Myeloma
Early-Late-nonablative
Koen van Besien, MD, PhDWeill Cornell Medical College
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Optimal Use of Transplant for Myeloma
Transplant Early!
Consider Allogeneic Transplant!
Koen van Besien, MD, PhDWeill Cornell Medical College
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Why Transplant Early?
• It is the standard• It is less toxic than alternatives• It is curative therapy
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High-Dose Therapy and Autologous SCT Improves PFS and OS in Younger Patients
Child JA, et al. N Engl J Med. 2003;348:1875-1883.; Attal M, et al. N Engl J Med. 1996;335:91-97.
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ASCT vs. Conventional CTResults of Randomized Studies
Attal, et al. 1996 IFM90CT
Auto Tx
Fermand, et al. 2005 MAG91CT
Auto Tx
Child, et al. 2003 MRC7CT
Auto Tx
Palumbo, et al. 2004 IMMSGCT
Auto Tx
Blade, et al. 2005 PETHEMACT
Auto Tx
Barlogie, Kyle, et al. 2006 USIGCT
Auto Tx
100
100
96
94
200
201
98
97
83
81
255
261
5
22
18
27
20
36
19
25a
9
44
20
32
6
25
16
28
11
30
33
42
11
11
16%at 7
years17%
44
57
48
48
42.3
54.1
43
58+
66
61
38%at 7
years38%
.03
.03
< .001
Patients(n)
OS(months) P Value
EFS(months)
CR(%)
CT = chemotherapy; Auto Tx = autologous therapy; IFM = Intergroupe Francais du Myelome; IMMSG = Italian Multiple Myeloma Study Group; MAG = Group Myelome Autographe; MRC = Medical Research Council; USIG = US Intergroup
aP = .07
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Why Transplant Early?
• It is the standard.• It is less toxic than alternatives• It is curative therapy
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0
10
20
30
40
50
60
70
Estimated medianOS
Median EFS TWiSTT*
PSCT (early)
PSCT (late)
Mon
ths
HDT/PSCT: Upfront vs. Rescue Treatment Show Similar OS but Better QOL with Early SCT
*Time without symptoms and treatment toxicity Fermand J, et al. Blood. 1998;92:3131-3136
64.6 64.0
39.0
13.0
27.822.3
P = .92
n=202
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14
Impact of ASCT on QOL of FL patients
Andresen et alLeuk & Lymph, 2012; 53: 386
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Why Transplant Early?
• It is the standard• It induces more remissions• It is curative therapy
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Martinez-Lopez et al Blood. 2011;118(3):529-534
CR vs. nCR/VGPR/PR vs. Menos
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Martinez-Lopez et al Blood. 2011;118(3):529-534
Abstract
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Why Transplant Early?
• It is the standard• It is less toxic than alternatives• Delaying curative therapy until after disease
recurrence may result in loss of curability
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• Refractory Myeloma
• Transient antitumor effect CTX, then TBI, thiotepa with T-cell depleted allograft
• Progressive disease was documented before day 70
• 2nd DLI resulted in complete disappearance of any disease
• GVHD developed revealing a GVM effect
Tricot G. Blood 87;3 1996 1196-1198.
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Allo Tx
• Graft vs. Myeloma• Syngeneic Transplant
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Trasplante Syngeneico
Bashey et al, BBMT 20089
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Allo Tx
• Graft vs. Myeloma• Syngeneic Transplant• Myeloablative:
• Less disease recurrence -Abandoned
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Allo Tx
• Graft vs. Myeloma• Syngeneic Transplant• Myeloablative• Non-Myeloablative
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Bjorkstrand et al, JCO 29;22: 3016-3022
Fludarabine 30mg/m2, 2Gy TBI, MMF, CSA
DLI 3 months PR
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Allo-RIC vs. Auto Study N Eligib
TXCond GVH
N Tx
Age PFS Surv
Hovon 260 HLA sib 2 Gy TBICSA-MMF
99 54 28%@ 6y22%@ 6y
55%@ 6y55%@ 6y
Gimema 120 HLA sib 2Gy TBI 60 50@ 4y25@ 4y
60@ 4y45@4 y
CTN 700+ HLA sib 2GyTBICSA-MMF
156 43@ 3y46 @ 3y
77@ 3y80@ 3y
EBMT-NMAM
375 HLA-sib Flu 2 Gy TBICSA-MMF
109 22 @8y12@8y
49@ 8y36@ 8y
IFM 284* HLA Sib BU 4 Flu ATGCSA-MTX
65 54 19@5y22@5y
40@ 5y45@5y
PETHEMA
110** HLA-sib Flu-Mel 140 25 52 60%@5y25%@5y
60%@5y60%@5y
* Only B2M >3 and 13q del ** no nCR after Tx1
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Allo-RIC vs. Auto Study N Eligib
TXCond GVH
N Tx
Age PFS Surv
Hovon 260 HLA sib 2 Gy TBICSA-MMF
99 54 28%@ 6y22%@ 6y
55%@ 6y55%@ 6y
Gimema 120 HLA sib 2Gy TBI 60 50@ 4y25@ 4y
60@ 4y45@4 y
CTN 700+ HLA sib 2GyTBICSA-MMF
156 43@ 3y46 @ 3y
77@ 3y80@ 3y
EBMT-NMAM
375 HLA-sib Flu 2 Gy TBICSA-MMF
109 22 @8y12@8y
49@ 8y36@ 8y
Blood 2012 119, 6219Blood 2011,;117,6721Lancet Oncol 2011, 12,1195Blood 2013, 121, 5055
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Auto-RIC vs. Auto: RelapseHovon Gimema
EBMT
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Auto RIC vs. Auto: Survival
Gimema
Hovon
CTN EBMT
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EBMT: Myeloma with 13q
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PETHEMA:PFS After Allo vs. 2nd Auto in <nCR
Rossinol Blood 2008
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OS from the time of first relapse/progression in patients with multiple myeloma treated with auto/RICallo or auto alone.
Gahrton G et al. Blood 2013;121:5055-5063
©2013 by American Society of Hematology
Survival after relapse is Superior in patients undergoing Allogeneic Transplant
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Graft vs. Myeloma Optimized?
Tricot G. Blood 87;3 1996 1196-1198.
Lenalidomide?Pomalidomide?Vaccines?
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Conclusions• Toxicity of allogeneic Transplant has been
reduced in recent years• With prolonged follow-up the benefit of allo
transplant becomes more apparent.• Allogeneic Transplant is particularly attractive
for poor prognosis patients.• The future:
• Alternative donors• Avoidance of chronic GVHD• Early Allogeneic Transplant• Incorporation of Maintenance Strategies
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Case 1• 35 YoF• MM del 17p, IgG• 2012 Auto: PR• Relapse• VDT-PACE: PR• Haplo cord:
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Case 2
• MM IgA• ET• Chloroma• Cytarabine-Arac +
Bortezomib• PR• URD Transplant
Tx in 1st remissionNl cytogenetics
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Conclusions• Autologous transplant remains the standard
treatment for myeloma• It is well tolerated and may lead to superior
QOL• Cure may be possible in a fraction of
patients• Allogeneic transplantation should be
considered, particularly in patients with adverse prognosis