the european group for blood and marrow transplantation

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


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



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



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



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



• 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



• 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



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



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 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



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



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



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%


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)



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



• 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)



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




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%


0.0

0.1

0.2

0.3

0.4

0.5

0 2 4 6 8 10


Cu

m I

nc

Se

c M

alig

nan

cy

8.4%

Secondary malignanciesSecondary malignancies



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


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


73%73%

52%52%

84%84%77%77%

Progression Free And Overall Survival - ASCTProgression Free And Overall Survival - ASCT




0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6 7 8


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


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




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




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



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



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



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




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




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


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




0.0

0.2

0.4

0.6

0.8

1.0


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


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)




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


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


15%15%19%19%

WM Allo-SCT Relapse / Progression (n=86)WM Allo-SCT Relapse / Progression (n=86)




0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6 7 8



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


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


61%61%

52%52%



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



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



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



0,00

0,25

0,50

0,75

1,00

0 12 24 36 48 60 72 84Months post-SCT

Cu

mu

lati

ve In

cid

ence

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



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

lati

ve S

urv

ival

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



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

lati

ve s

urv

ival

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



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

lati

ve S

urv

ival

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



ASCT

RIC-Allo-SCT

MAC-Allo-SCT

Overall Survival: ASCT - RIC – MAC - Allo- SCTOverall Survival: ASCT - RIC – MAC - Allo- SCT

Months post-SCT

Cu

mu

lati

ve s

urv

ival

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



• 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



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

Industry

Voluntary sector

Professionals

Patients / Families

the european group for blood and marrow transplantation

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