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The European Group for Blood and Marrow Transplantation. STEM CELL TRANSPLANTATION FOR PATIENTS WITH WALDENSTROM’S MACROGLOBULINEMIA (WM) Dr Charalampia Kyriakou MD, PhD. WALDENSTROM’S MACROGLOBULINEMIA. Rare Indolent Lymphoma - PowerPoint PPT Presentation
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The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011The European Group for Blood and Marrow TransplantationThe European Group for Blood and Marrow Transplantation
STEM CELL TRANSPLANTATION FOR PATIENTS STEM CELL TRANSPLANTATION FOR PATIENTS WITH WALDENSTROM’S MACROGLOBULINEMIA WITH WALDENSTROM’S MACROGLOBULINEMIA
(WM)(WM)
Dr Charalampia Kyriakou MD, PhD
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
WALDENSTROM’S MACROGLOBULINEMIAWALDENSTROM’S MACROGLOBULINEMIA
Rare
Indolent Lymphoma
Median presentation age 63 years-often have ongoing morbidities from other diseases
Smoldering - Asymptomatic WM - NO TREATMENT
Conventional Therapies up to 90% response, short duration and low CR rates
No cure
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
WALDENSTROM’S MACROGLOBULINEMIAWALDENSTROM’S MACROGLOBULINEMIAISSWMISSWM
Adverse covariates: .Age>65 . Hb≤11.5g/dL .Plt≤100x109/L .IgM>70g/L .Β2-M>3mg/L ?LDH ?CRP ?Previous Line therapies
Risk Score * No of pts (%) {n=587 Median FU 5.3yrs} 5yrs survival (%) Low ≤1, Age<65 155(27) 87
Intermediate 2 or Age>65 224(38) 68
High >2 208(35) 36
Risk- LDH-Previous Rx Lines- LDH-Previous Rx Lines ** No of pts (%) {n=183 Median FU 10yrs} 8yrs survival(%)Low - Normal LDHNormal LDH 98 55
Low-Intermediate – High LDHHigh LDH 51 33
High - Normal LDH Normal LDH 29 5
High - High LDH High LDH 4 0
*Morel et al; Blood 113:4163-4170, 2009**Dhodapkar et al; Blood 113:793-796,2009
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Regimen / Reference No of Pts Study ORR %
Chlorambucil / Facon et al ,JCO 1993 128 Retrospective 31
Cladribine / Weber et al, Semin Oncol 2003 46 Prospective Phase II 45
Fludarabine / Dhodapkar et al, Semin Oncl 2003 172 Prospective Phase II 38
Fludarabine vs CAP / Leblond et al , Blood 2001 45/45 Prospective Phase II 30/11
Rituximab / Gertz et al, Clin Ly My 2004 69 Prospective Phase II 52
Rituximab / Dimopoulos et al, JCO 2002 29 Prospective Phase II 48
Bortezomib / Chen et al ,JCO 2007 27 Prospective Phase II 52
Bortezomib / Treon et al , Clin Cancer Res 2007 27 Prospective Phase II 48
Treatment For Symptomatic WMTreatment For Symptomatic WM
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Author N of pts Schedule ORR % TTF
Dimopoulos et al, JCO 2007
72 Dex/Rituximab/Cyclo83% (7%CR,67%PR)
At 2yrs 67%
Buske et al, Leukemia 2009 25/25 CHOP vs R-CHOP60%- 3%CRvs
91%-9%CR1.9vs 5.2 yrs
Rummel et al,
German Subgroup Indolent Lymphoma StiL
23/17R-Bendamustine vs
R-CHOP96%vs 94%
PFS at 3yrs
82%vs 58%
Treon et al, Blood 2009 43 Fludarabine/Rituximab 86%-2%CR 4.5 yrs
Treon et al, Blood 2009 25Thalidomide/
Rituximab70%-4%CR 3yrs
Treon et al, JCO 200924
Bortezomib/Dex/
Rituximab83%- 22%CR-nCR NR (FU 2yrs)
Treon et al, ASH 2009 240Rituximab Maintenance
vs Observation61.3 vs 22.6(m)
TREATMENT FOR SYMPTOMATIC WMTREATMENT FOR SYMPTOMATIC WM
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
• Anagnostopoulos et al Biol Blood Marrow Transplant. Aug;2006
• Tournilhac et al Semin Oncol. Apr;2003
• P. Dreger, N. Schmitz Biol Blood Marrow Transplant. May;2007
• David Maloney; IWMW;Venice, Italy ,2010
STEM CELL TRANSPLANTATION FOR WM PATIENTSSTEM CELL TRANSPLANTATION FOR WM PATIENTS
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
• Deliver high - lethal dose chemo-radio therapy to destroy tumour Deliver high - lethal dose chemo-radio therapy to destroy tumour
cellscells
• Provide a source of haemopoietic stem cells to salvage the ablated Provide a source of haemopoietic stem cells to salvage the ablated
marrowmarrow
• Establish organ graft tolerance to prevent rejection of donor cellsEstablish organ graft tolerance to prevent rejection of donor cells
• Provide immune effector cells to mediate graft-vs-tumour activityProvide immune effector cells to mediate graft-vs-tumour activity
Haematopoietic Stem Cell Transplantation Haematopoietic Stem Cell Transplantation ObjectivesObjectives
E.D. Thomas et al, N. Engl. J. Med. 257, 491-496 (1957)Intravenous Infusion of Bone Marrow in Patients Receiving Radiation and ChemotherapyIntravenous Infusion of Bone Marrow in Patients Receiving Radiation and Chemotherapy
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Autologous/Allogeneic Stem Cell Autologous/Allogeneic Stem Cell TransplantationTransplantation
• Cells either obtained from G-CSF/+ Chemotherapy (for ASCT) mobilised Cells either obtained from G-CSF/+ Chemotherapy (for ASCT) mobilised peripheral blood stem cells or bone marrow harvestperipheral blood stem cells or bone marrow harvest
• Requires HLA-matched donorRequires HLA-matched donor– Matched sibling (25% chance of matching any sibling)Matched sibling (25% chance of matching any sibling)– Umbilical cord blood cellsUmbilical cord blood cells– Mismatched donorsMismatched donors– Matched unrelated donorMatched unrelated donor
• Search International donor registriesSearch International donor registries
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Regimen Intensity for Allogeneic Stem Cell Regimen Intensity for Allogeneic Stem Cell
TransplantationTransplantationIm
mu
no
sup
pre
ssiv
eIm
mu
no
sup
pre
ssiv
e
MyelosuppressionMyelosuppression
Flu / TBI 2GyFlu / TBI 2Gy
Flu / CyFlu / Cy
Flu / Mel / CampathFlu / Mel / Campath
Flu / Bu / ATGFlu / Bu / ATG
BEAMBEAMCampathCampath
FLAG / IdaFLAG / Ida
TBI 2GyTBI 2Gy
Cy / TBICy / TBIBy/TBIBy/TBIMelp/VP16/TBIMelp/VP16/TBICyclo/VP16/BCNUCyclo/VP16/BCNU
Reduced IntensityReduced Intensity
Conventional MyeloblativeConventional Myeloblative
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
The Perfect Transplant RegimenThe Perfect Transplant Regimen
Low toxicity and TRMLow toxicity and TRM
Low incidence of GVHDLow incidence of GVHD
High level of tumour controlHigh level of tumour control
Good immune reconstitutionGood immune reconstitution
Disease responds to DLIDisease responds to DLI
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Sources of Stem Cell TransplantationSources of Stem Cell Transplantation
AutologousAutologous• Donor availableDonor available
• No GVHDNo GVHD
• No ImmunosuppressionNo Immunosuppression
Less toxicity
Higher relapse rates
AllogeneicAllogeneic
• Stem cells free of WMStem cells free of WM
• Undamaged stem cellsUndamaged stem cells
• Immune mediated graft-vs-tumour effectImmune mediated graft-vs-tumour effect
• Replaces damaged host haemopoiesisReplaces damaged host haemopoiesis
• DLI may provide augmented anti-WM DLI may provide augmented anti-WM
activityactivity
• May be curativeMay be curative
More toxicity, GVHDMore toxicity, GVHD
Lower Relapse ratesLower Relapse rates
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Questions ???Questions ???
Can Stem Cell Transplantation be used as a curative approach to WM?Can Stem Cell Transplantation be used as a curative approach to WM?WHOWHO ?Indication?Indication ?Risk-benefit?Risk-benefit ?Recipient Performance Status, Specific HCT comorbidity index, risk score ?Recipient Performance Status, Specific HCT comorbidity index, risk score
for mortalityfor mortalityWHENWHEN
?Not too early not too late ? “frontline”?Not too early not too late ? “frontline” ?Age?Age ?Response target? Cure ? Significance of disease status pre-post on the ?Response target? Cure ? Significance of disease status pre-post on the
overall managementoverall management ?Long term risks?Long term risks TYPETYPE
?Conditioning ?Auto ?Allo ?MAC ?RIC?Intensity?SIB?MUD?Conditioning ?Auto ?Allo ?MAC ?RIC?Intensity?SIB?MUD ?GVHD prophylaxis ?purging?GVHD prophylaxis ?purging
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
ALLOGENEIC STEM CELL TRANSPLANTATION FOR HIGH ALLOGENEIC STEM CELL TRANSPLANTATION FOR HIGH RISK WM PATIENTS (n=25, MAC:12, RIC:13) RISK WM PATIENTS (n=25, MAC:12, RIC:13)
Garnier et alGarnier et al, , Haematologica 2010Haematologica 2010
Median FU: 64 (11-149) months , Heavily pre-treated, 44% chemorefractory DxMedian FU: 64 (11-149) months , Heavily pre-treated, 44% chemorefractory Dx
67%67% 67%67%
25%25%
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011Garnier et alGarnier et al, , Haematologica 2010Haematologica 2010
Allogeneic Stem Cell Transplantation Allogeneic Stem Cell Transplantation For High Risk WM Patients (n=25) For High Risk WM Patients (n=25)
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
EBMT Lymphoma Registry WM-SCT ActivityEBMT Lymphoma Registry WM-SCT Activity1995-20071995-2007
0
10
20
30
40
50
60
1995 1997 1999 2001 2003 2005 2007
Allo-SCTAuto-SCT
SCT activity by year of SCT
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
• Median Follow-up for the surviving pts, years (range): 4.2 (0.5- 14.8)
• Alive: n= 107 (68%) No progression: n=78 (49%) Relapse or progression: n=71(45%)
• Time to relapse or progression: 15m (1-110)
• Dead: 51 (32%) Disease progression: 42 (26%)
Non-disease Progression: 9 (8%)Infection:6, MOF:2, Cardiac:1
Secondary MalignanciesSecondary Malignancies: 10 (6.3%) [AML: 1, MDS: 4, Melanoma: 1,Prostate Ca: 1, Small Cell Lung Ca: 1, Other solid tumors: 2]
Kyriakou et al, JCO 2010Kyriakou et al, JCO 2010
WM ASCT – RESULTS (n=158) WM ASCT – RESULTS (n=158)
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Post- Autologous Stem Cell Transplantation (ASCT) Outcome Post- Autologous Stem Cell Transplantation (ASCT) Outcome by disease status at the time of ASCT (n=158) by disease status at the time of ASCT (n=158)
Disease status at ASCTDisease status at ASCT TotalTotal
VGPR1VGPR1 >VGPR2>VGPR2 Chemosensitive Chemosensitive diseasedisease
ChemorefractoryChemorefractorydiseasedisease
CRCR 1010 33 2121 00 3434
VGPRVGPR 2020 1919 3636 22 7777
PRPR 00 00 1818 55 2323
No response (SD/Prog) No response (SD/Prog) 44 00 1111 33 1818
NENE 00 00 22 11 33
NANA 00 00 33 00 33
TotalTotal 3434 2222 9191 1111 158158
Kyriakou et al, JCO 2010Kyriakou et al, JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Non Relapse Mortality – Relapse Rate - ASCTNon Relapse Mortality – Relapse Rate - ASCT
1.0
0.0
0.2
0.4
0.6
0.8
0 1 2 3 4 5 6 7 8
Time after ASCT (years)
Cu
mu
lati
ve
Inid
enec
e
NRMNRM
Relapse or ProgressionRelapse or Progression
52%52%
4.6%4.6%5.6%5.6%
3.8%3.8%
Kyriakou et al, JCO 2010Kyriakou et al, JCO 2010
0.0
0.1
0.2
0.3
0.4
0.5
0 2 4 6 8 10
Time after ASCT (years)
Cu
m I
nc
Se
c M
alig
nan
cy
8.4%
Secondary malignanciesSecondary malignancies
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0.0
0.2
0.4
0.6
0.8
1.0
Pro
bab
ilit
y o
f S
urv
ival
PFS: ALL PTSPFS: ALL PTS
OS: ALL PTSOS: ALL PTS
0 1 2 3 4 5 6 7 8
Time after ASCT (years)
68.5%68.5%
41%41%
77.6%77.6%
61.7%61.7%
0.0
0.2
0.4
0.6
0.8
1.0
Pro
bab
ilit
y o
f S
urv
ival
PFS: VGPR1, PR1PFS: VGPR1, PR1
OSOS:VGPR1, PR1:VGPR1, PR1
0 1 2 3 4 5 6 7 8
Time after ASCT (years)
73%73%
52%52%
84%84%77%77%
Progression Free And Overall Survival - ASCTProgression Free And Overall Survival - ASCT
Kyriakou et al, JCO 2010Kyriakou et al, JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5 6 7 8
Time after ASCT (years)
PF
SP
FS
Landmark: 6 months
- IF (n=33)
+ IF (n=18)
p=0.08
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5 6 7 8
Time after ASCT (years)
Ove
rall
Su
rviv
alO
vera
ll S
urv
ival
Landmark: 6 months
- IF (n=33)
+ IF (n=18)
n.s.
Progression Free And Overall Survival Progression Free And Overall Survival By ImmunofixationBy Immunofixation
Kyriakou et al, JCO 2010Kyriakou et al, JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Adverse prognostic Factors for Post ASCT Outcome: Adverse prognostic Factors for Post ASCT Outcome: Multivariate analysis Multivariate analysis
Adverse prognostic factorAdverse prognostic factor Relative riskRelative risk Confidence Confidence intervalinterval
P valueP value
Relapse / ProgressionRelapse / Progression ≥ 3 prior lines of therapy Refractory disease at ASCT
2.5 3.9
1.5 – 4.1 1.6 – 9.4
0.0010.003
Progression free survivalProgression free survival ≥ 3 prior lines of therapy Refractory disease at ASCT
2.4 4.1
1.5 – 3.9 1.8 – 9.2
0.001< 0.001
Overall survivalOverall survival Male sex ≥ 3 prior lines of therapy Age at ASCT > 60 years Refractory disease at ASCT
2.03.11.93.1
1.1 – 3.91.7 – 5.91.0. - 3.81.2 – 8.1
0.040.0010.050.03
Kyriakou et al, JCO 2010Kyriakou et al, JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
7260483624120
Months after ASCT
1.0
0.8
0.6
0.4
0.2
0.0
PR
OG
RE
SS
ION
FR
EE
SU
RV
IVA
LP
RO
GR
ES
SIO
N F
RE
E S
UR
VIV
AL
Chemosensitive Chemosensitive
Chemorefractory Chemorefractory
p<0.001
7260483624120
Months after ASCT
1.0
0.8
0.6
0.4
0.2
0.0
OV
ER
AL
L S
UR
VIV
AL
OV
ER
AL
L S
UR
VIV
AL
Chemosensitive diseaseChemosensitive disease
Chemorefractory diseaseChemorefractory disease
p<0.001
Progression Free and Overall Survival By disease Progression Free and Overall Survival By disease Status at ASCTStatus at ASCT
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
EBMT Lymphoma Registry: Allo-SCT-WM: 2000-2007 EBMT Lymphoma Registry: Allo-SCT-WM: 2000-2007
(n=86; MAC:37, RIC:49 pts)(n=86; MAC:37, RIC:49 pts)
Allo-SCT: Conditioning by year of SCT
0%
25%
50%
75%
100%
2000 2001 2002 2003 2004 2005 2006 2007
MAC
RIC
32% Chemo-refractory disease, 47% High and 19% Intermediate risk Dx, 10% poor 32% Chemo-refractory disease, 47% High and 19% Intermediate risk Dx, 10% poor performance statusperformance status
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
CharacteristicsCharacteristics Patient NoPatient No
Median Follow up for surviving pts – range: Median Follow up for surviving pts – range: 50 (7-142) months50 (7-142) months
AliveAlive
Median time to response:Median time to response: 6 months (range:2-50) 6 months (range:2-50)
Disease ResponseDisease ResponseCRCRVGPRVGPRPRPRSD/PDSD/PDNE(early deaths)NE(early deaths)
Dead NRM NRM Disease relapse/progressionDisease relapse/progression
5656
15153333171766
1515
3030232377
WM Allo-SCT - Results WM Allo-SCT - Results
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
CharacteristicsCharacteristics Patient NoPatient No
Relapse / ProgressionRelapse / Progression
Median time to relapse:Median time to relapse: 9 months (2-89)
Donor Lymphocyte InfusionDonor Lymphocyte Infusion Persistent disease/Relapse Mixed chimerism Bone marrow failure
Median time from SCT to DLI:Median time from SCT to DLI: 9 months (1-90)
Response to DLI for DiseaseResponse to DLI for Disease (n=14) – OR: 80%CRPRNo responseNE
1919
212114146611
77442211
WM Allo-SCT - Results – Donor Lymphocyte InfusionWM Allo-SCT - Results – Donor Lymphocyte Infusion
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
OutcomeOutcome Whole series (n = 86)Whole series (n = 86) MAC (n = 37)MAC (n = 37) RIC (n = 49)RIC (n = 49) pp value value
Acute GVHDAcute GVHD100-days CI of aGVHD
Chronic GVHDChronic GVHD Absent Limited Extensive 18-mo CI of cGVHD (95% confidence interval)
45%45% (35 - 56)
41(48%)9(11%)
19(22%)41% (31% - 55%)
61%61% (47 - 79)
15(41%)6(16%)6(16%)
45%45% (30 - 69)
33%33% (22 - 49)
26(53%)3(6%)
13(27%)36% (24 - 64)
0.0010.001
n.s.n.s.
Results Post Allo-SCT - GVHD Results Post Allo-SCT - GVHD
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5 6
Years after Allo-SCT
RE
LA
PS
E O
R P
RO
GR
ES
SIO
NR
EL
AP
SE
OR
PR
OG
RE
SS
ION
cGVHD (n=21)cGVHD (n=21)
No cGVHD (n=31)No cGVHD (n=31)
6 mo
p=0.03p=0.03
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5 6
PR
OG
RE
SS
ION
FR
EE
SU
RV
IVA
LP
RO
GR
ES
SIO
N F
RE
E S
UR
VIV
AL
Years after Allo-SCT
No cGVHD (n=31)No cGVHD (n=31)
cGVHD (n=21)cGVHD (n=21)
6 mo
p=0.1p=0.1
Impact Of Chronic - GVHD On Relapse Rate Impact Of Chronic - GVHD On Relapse Rate And Progression Free SurvivalAnd Progression Free Survival
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0.0
0.2
0.4
0.6
0.8
1.0
Years after Allo-SCT
NR
MN
RM
RIC (n=49)RIC (n=49)
MAC (n=37)MAC (n=37)
0 1 2 3 4 5 6 7 8
p: n.s.p: n.s.
0.0
0.2
0.4
0.6
0.8
1.0
Years after Allo-SCT
NR
MN
RM
0 1 2 3 4 5 6 7 8
Whole series (n=86)Whole series (n=86)
23%23%27%27%
WM Allo-SCT Non - Relapse Mortality (n=86)WM Allo-SCT Non - Relapse Mortality (n=86)
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0.0
0.2
0.4
0.6
0.8
1.0
RE
LA
PS
E O
R P
RO
GR
ES
SIO
N
RIC (n=49)RIC (n=49)
MAC (n=37)MAC (n=37)
0 1 2 3 4 5 6 7 8
Years after Allo-SCT
p: n.s.
0.00.0
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
00 11 22 33 44 55 66 77 88
Years after Allo-SCTYears after Allo-SCT
RE
LA
PS
E O
R
PR
OG
RE
SS
ION
RE
LA
PS
E O
R
PR
OG
RE
SS
ION
Whole series (n=86)Whole series (n=86)
15%15%19%19%
WM Allo-SCT Relapse / Progression (n=86)WM Allo-SCT Relapse / Progression (n=86)
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5 6 7 8
Years after Allo-SCT
Whole series (n=86)Whole series (n=86)
72%72%
66%66% 64%64%
OV
ER
AL
L S
UR
VIV
AL
OV
ER
AL
L S
UR
VIV
AL
WM Allo-SCT Overall and Progression Free Survival WM Allo-SCT Overall and Progression Free Survival
Kyriakou et al; JCO 2010Kyriakou et al; JCO 2010
0.0
0.2
0.4
0.6
0.8
1.0
0 1 2 3 4 5 6 7 8
Years after Allo-SCTYears after Allo-SCT
PR
OG
RE
SS
ION
FR
EE
SU
RV
IVA
LP
RO
GR
ES
SIO
N F
RE
E S
UR
VIV
AL
Whole series (n=86)Whole series (n=86)
61%61%
52%52%
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
10 years experience on Stem Cell Transplantation 10 years experience on Stem Cell Transplantation in patients with Waldenstrom Macroglobulinemiain patients with Waldenstrom Macroglobulinemia
EBMT UpdateEBMT Update
Stem cell Transplantation (ASCT vs RIC vs MAC)Stem cell Transplantation (ASCT vs RIC vs MAC)
EBMT Database reported between Jan 2000- Jan 2010EBMT Database reported between Jan 2000- Jan 2010
First SCT procedureFirst SCT procedure
ASCTASCT n=424n=424
Allo SCTAllo SCT n=226n=226– RICRIC n=139n=139– MACMAC n=81n=81
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0,00
0,25
0,50
0,75
1,00
0 12 24 36 48 60 72 84
Months post-SCT
Cu
mu
lati
ve In
cid
ence
NRM: ASCT - RIC - MAC - Allo-SCTNRM: ASCT - RIC - MAC - Allo-SCT
ASCT
RIC-Allo-SCT
MAC-Allo-SCT
NRM (%)NRM (%) 12 mo12 mo 36 mo36 mo 60 mo60 mo
ASCTASCT 44 77 88
RIC Allo-SCTRIC Allo-SCT 1919 2222 2323
MAC Allo-SCTMAC Allo-SCT 2626 3232 3636
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
Clinical CharacteristicsClinical Characteristics ASCT (n= 410)ASCT (n= 410) Allo-SCT (n=223)Allo-SCT (n=223)
Median FU of survivors (months)Median FU of survivors (months) 12 (3-112)12 (3-112) 17 (1-108)17 (1-108)
Median time to relapse, months (range)Median time to relapse, months (range) 13 (1-76)13 (1-76) 6 (1-58)6 (1-58)
Alive Alive
Dead Dead
Disease relapse/progressionDisease relapse/progression
GVHDGVHD
InfectionsInfections
OtherOther
Secondary malignanciesSecondary malignancies
81 (%)81 (%)
19 (%)19 (%)
65.6 (%)65.6 (%)
N/AN/A
17 (%)17 (%)
11.1 (%)11.1 (%)
6.3 (%)6.3 (%)
65.6 (%)65.6 (%)
34.4 (%)34.4 (%)
29.9 (%)29.9 (%)
30 (%)30 (%)
30 (%)30 (%)
8.6 (%)8.6 (%)
1.5 (%)1.5 (%)
Response Response
CRCR
VGPRVGPR
PRPR
No response/Progressive DxNo response/Progressive Dx
58 (%)58 (%)
15 (%)15 (%)
27 (%)27 (%)
53.3 (%)53.3 (%)
22.4 (%)22.4 (%)
24.3 (%)24.3 (%)
Patient CharacteristicsPatient Characteristics
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0,00
0,25
0,50
0,75
1,00
0 12 24 36 48 60 72 84Months post-SCT
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RR: ASCT - RIC – MAC - Allo-SCTRR: ASCT - RIC – MAC - Allo-SCT
ASCT
RIC-Allo-SCT
MAC-Allo-SCT
RR ( % )RR ( % ) 12 mo12 mo 36 mo36 mo 60 mo60 mo
ASCTASCT 1717 3838 5757
RIC Allo-SCTRIC Allo-SCT 2222 2727 2727
MAC Allo-SCTMAC Allo-SCT 1717 1919 2222
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0,00
0,25
0,50
0,75
1,00
0 12 24 36 48 60 72 84 96 108 120
Months post-SCT
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PFS: ASCT – Allo - SCTPFS: ASCT – Allo - SCT
ASCT
Allo-SCT
PFS (%)PFS (%) 12 mo12 mo 36 mo36 mo 60 mo60 mo
ASCTASCT 78.578.5 61.361.3 43.643.6
Allo-SCTAllo-SCT 56.456.4 46.646.6 4545
p=0.001
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
0,00
0,25
0,50
0,75
1,00
0 12 24 36 48 60 72 84 96 108 120
Months post-SCT
Cu
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lati
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PFS: ASCT - RIC - MAC - Allo- SCTPFS: ASCT - RIC - MAC - Allo- SCT
ASCT
RIC-Allo-SCT
MAC-Allo-SCT
PFS (%)PFS (%) 12 mo12 mo 36 mo36 mo 60 mo60 mo
ASCTASCT 78.578.5 61.361.3 43.643.6
RIC Allo-SCTRIC Allo-SCT 58.358.3 48.148.1 48.148.1
MAC Allo-SCTMAC Allo-SCT 55.755.7 45.945.9 42.742.7
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
OS: ASCT - Allo- SCTOS: ASCT - Allo- SCT
ASCT
Allo-SCT
0,00
0,25
0,50
0,75
1,00
0 12 24 36 48 60 72 84 96 108 120
Months post-SCT
Cu
mu
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OS (%)OS (%) 12 mo12 mo 36 mo36 mo 60 mo60 mo
ASCTASCT 89.689.6 78.678.6 68.768.7
Allo-SCTAllo-SCT 76.776.7 58.258.2 56.456.4
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
ASCT
RIC-Allo-SCT
MAC-Allo-SCT
Overall Survival: ASCT - RIC – MAC - Allo- SCTOverall Survival: ASCT - RIC – MAC - Allo- SCT
Months post-SCT
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0,00
0,25
0,50
0,75
1,00
0 12 24 36 48 60 72 84 96 108 120
OS (%)OS (%) 12 mo12 mo 36 mo36 mo 60 mo60 mo
ASCTASCT 89.689.6 78.678.6 68.768.7
RIC Allo-SCTRIC Allo-SCT 73.773.7 61.461.4 58.258.2
MAC Allo-SCTMAC Allo-SCT 65.565.5 55.255.2 55.255.2
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
• Treatment answers from Collaborative International Randomised clinical trialsTreatment answers from Collaborative International Randomised clinical trials• Patients with high risk WM have poor prognosis with conventional therapyPatients with high risk WM have poor prognosis with conventional therapy • HDT and SCT should be considered as a therapeutic option for high risk WM patientsHDT and SCT should be considered as a therapeutic option for high risk WM patients
Autologous Stem Cell TransplantationAutologous Stem Cell Transplantation Low NRMLow NRM Prolonged PFS and OS. Prolonged PFS and OS. Significantly superior ASCT outcomes were observed in patients with chemosensitive Significantly superior ASCT outcomes were observed in patients with chemosensitive
disease transplanted early following 1st maximum responsedisease transplanted early following 1st maximum response Note risk for secondary malignancies but comparable to the published incidence with conventional Rx Note risk for secondary malignancies but comparable to the published incidence with conventional Rx Could be considered for selected younger patients with high risk disease Could be considered for selected younger patients with high risk disease
Allogeneic –Stem Cell TransplantationAllogeneic –Stem Cell Transplantation High transplant related toxicity - Compromised Overall and Progression Free SurvivalHigh transplant related toxicity - Compromised Overall and Progression Free Survival Consider Allo-SCT only for high risk WM younger and fit patients with relapse refractory disease Consider Allo-SCT only for high risk WM younger and fit patients with relapse refractory disease Acute GVHD incidence significantly higher for MAC leading to higher early NRM compared to RIC patientsAcute GVHD incidence significantly higher for MAC leading to higher early NRM compared to RIC patients Development of cGVHD is associated with significantly lower relapse rateDevelopment of cGVHD is associated with significantly lower relapse rate Disease response following DLI for relapse disease together with the impact of cGVHD suggest Graft versus WM Disease response following DLI for relapse disease together with the impact of cGVHD suggest Graft versus WM
effecteffect
ConclusionsConclusions
The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation
London, January 2011
TREATMENT GOALS FOR WM PATIENTSTREATMENT GOALS FOR WM PATIENTS
• Obtain maximum response – improve outcomeObtain maximum response – improve outcome
• Improve duration of responseImprove duration of response
• Prevent reduce complications – reduce late effectsPrevent reduce complications – reduce late effects
• Maintain quality of lifeMaintain quality of life
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