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Hematopoietic Stem Cell Transplantation: High Risk Diffuse Large Cell Lymphoma:. Ginna G. Laport, MD Associate Professor of Medicine Division of Blood & Marrow Transplantation Stanford University Medical Center.

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hematopoietic stem cell transplantation high risk diffuse large cell lymphoma
Hematopoietic Stem Cell Transplantation:High Risk Diffuse Large Cell Lymphoma:

Ginna G. Laport, MD

Associate Professor of Medicine

Division of Blood & Marrow Transplantation

Stanford University Medical Center

diffuse large b cell lymphoma stem cell transplantation for high risk patients
Diffuse Large B-Cell Lymphoma:Stem Cell Transplantation for High Risk Patients
  • Identifying “High Risk” Patients
  • Autologous HSCT in High Risk Patients
    • Phase II Trials
    • Phase III Trials
  • Allogeneic HCT
diffuse large b cell lymphoma
Diffuse Large B-Cell Lymphoma
  • Most common NHL: 31%
    • Peak incidence in 6th decade
  • Large cells with loss of follicular architecture of node
    • 30% to 40% present with rapidly enlarging, symptomatic mass with B symptoms
  • Frontline chemotherapy (anthracycline-based + RTX)
    • CR  50-60%
    • Long term remission -> 30-35%
overall survival according to revised international prognostic index
Overall Survival According to Revised International Prognostic Index
  • Age >60
  • PerfStatus
  • Stage 3-4
  • LDH
  • Extranodal

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

P < .001

0

0

1

2

3

4

5

Yrs

Sehn LH, et al. Blood. 2007;109:1857

survival by gene expression profiling dlbcl
Survival by Gene Expression Profiling: DLBCL

Diffuse Large B-Cell Lymphoma

1.0

0.8

0.6

OS

0.4

0.2

0

0

2

4

6

8

10

Yrs

Rosenwald A, et al. J Exp Med. 2003;198:851-862.

prognosis by interim pet scanning
Prognosis By Interim PET Scanning
  • Mixed results seen in 4 studies
  • 2 studies confirm predictive value, 2 studies did not

Progression Free Survival

n= 98

Progression Free Survival

n= 112

1.0

100

  • PET Negative
  • PET negative (n=73)

0.8

80

  • PET Positive

0.6

60

  • PET positive (n=12)

40

0.4

20

0.2

  • P=0.02
  • P=0.146

0

0

0

20

40

60

80

100

0

1

2

3

4

5

6

7

Moskowicz et al. J ClinOncol 2010;11: 1896

Time (months)

Time (years)

Safar et al, J ClinOncol 2012;30:184

high risk diffuse large cell lymphoma
High Risk DiffuseLarge Cell Lymphoma

Autologous

HSCT in First CR/PR

high risk diffuse large b cell nhl frontline autologous hct phase ii trials containing rituximab
High Risk Diffuse Large B Cell NHL:Frontline Autologous HCTPhase II Trials containing rituximab
meta analysis autologous hsct as front line therapy
Meta-analysis:Autologous HSCT as Front Line Therapy

Cochrane Database Sys Rev 2008;CD004024

N = 2228

No survival advantage for autologous HSCT in CR1

Haematologica 2003;88:1304

N = 3079

Overall survival advantage for autologous HSCT in CR1

compared to chemotherapy

r chop x 8 vs r chop x 6 cycles autologous hsct swog s9704
R-CHOP x 8 vsR-CHOP x 6 Cycles + Autologous HSCT (SWOG S9704)

Eligibility: Bulky stage 2-4 Hi-int/High IPI

CHOP ± Rituximab x 1

+ Autologou HSCT*

(n = 125)

Ptswith ≥ PR after CHOP ± RTX x 5

(N = 253)

CHOP ± Rituximab x 3

(n = 128)

Stiff PJ, et al. ASCO 2011. Abst 8001.

asct after chop rtx improves pfs in advanced high risk diffuse nhl
ASCT After CHOP ± Rtx Improves PFS in Advanced High-Risk Diffuse NHL
  • Autologous HSCT prolonged PFS
    • high-intermediate
    • high-IPI
  • Autologous HSCT prolonged OS
    • high-IPI

Stiff PJ, et al. ASCO 2011. Abstr 8001.

italian lymphoma foundation 2 x 2 randomized trial with autologous hsct in high risk patients
Italian Lymphoma Foundation2 x 2 Randomized Trial with Autologous HSCT inHigh Risk Patients

R-CHOPx 3

R

A

N

D

O

M

IZE

R

A

N

D

O

M

I

Z

E

BEAM  AutoHCT

PR, CR

Newly diagnosed

DLBCL,

aaIPI> 2

n = 399

Observation only

R-megaCHOP

SD, PDoff study

Ann Oncol 2011; 22 suppl 4: abstr 72.

slide15

Italian Lymphoma Foundation2 x 2 Randomized Trial with Autologous HCT in High Risk Patients(median followup = 23 mos)

Progression Free Survival

1.00

HDT

0.75

0.50

No-HDT

0.25

P=.008

0.00

0

6

12

18

24

30

36

42

48

Months

- Risk of relapse was 53% lower in BMT patients

- No overall survival difference between two arms`

slide16

High Risk DiffuseLarge Cell Lymphoma

  • Is there a role for allogeneic HSCT??
survival after allogeneic hct for diffuse large b cell lymphoma 2000 2009 by disease status
Survival after Allogeneic HCT for Diffuse Large B-Cell Lymphoma, 2000-2009- By Disease Status -

100

100

90

90

80

80

70

70

60

60

Probability of Survival, %

50

50

Sensitive (N=383)

40

40

30

30

20

20

Resistant (N=124)

10

10

P < 0.0001

0

0

1

3

0

2

4

5

6

Years

reduced intensity allogeneic hsct after autologous hsct relapse
Reduced Intensity Allogeneic HSCT (after autologous HSCT relapse)
  • Factors affecting outcomes
    • Dz status at time of allogeneic HCT
    • Time to relapse after autologous HCT (< 12 m vs > 12 m)
  • Did not affect outcome
    • Prep regimen

Rigacci et al , Ann Heme 2012;91:931

van Kampen et al. JCO 2011;29:1342

hematopoietic sct for high risk dlbcl
Hematopoietic SCT for High Risk DLBCL
  • Need better tools to identify high risk patients
  • Current studies suggest that high-IPI subtype may benefit from autologous HCT early as front line therapy
  • More studies needed to further define role of autologous HSCT as front line therapy
    • Need study that includes only ABC-subtype
  • Role of allogeneic HSCT in high risk population?
coral trial collaborative trial in relapsed aggressive lymphoma
CORAL Trial:Collaborative Trial in Relapsed Aggressive Lymphoma

Which salvage regimen is the best?

R-ICEx 3

R

A

N

D

O

M

IZE

R

A

N

D

O

M

I

Z

E

Rituximab

q2mos x 6

Auto

SCT

PR, CR

Relapsed/ refractory

DLBCL

n = 396

Observation only

R-DHAPx 3

SD, PDoff study

Role of maintenance

rituximab

J ClinOncol 2010; 28:4184–4190.

coral trial survival according to salvage regimen
CORAL TrialSurvival according to Salvage Regimen

OverallSurvival

Event Free Survival

1.0

1.0

0.8

0.8

R-ICER-DHAP

0.6

0.6

0.4

0.4

0.2

0.2

P = .49

P = .27

0

0

0

12

24

36

48

60

72

0

12

24

36

48

60

72

Mos

Mos

GCB vs ABC 3 yr PFS: 70% vs 28%

R-DHAPvs R-ICE in GCBpts: 3 yrPFS:100% vs 27%

slide23

CORAL Trial:

EFS byrelapse timeafter initial therapy

Relapse > 12 mos fromdx

Relapse < 12 mos fromdx

Relapse < 12 mos from dx

predicted for poor outcome after autologous HCT

slide24

EFS

PFS

Female

RTX

Obs

Male

p=.74

p=.04

Female pts benefited from RTX maintenance

JCO 2012, In press

coral factors affecting survival in relapsed dlcl patients
CORAL: Factors affecting survival in relapsed DLCL patients

EFS OS

Prior rituximab.0007 .01

Relapse < 12 mos<.0001 <.0001

sIPI<.0004 <.0001

R-DHAP vs R-ICE0.3 0.7

(Except for GCB pts)

p

parma study bmt vs salvage chemotx for relapsed dlbcl
PARMA Study: BMT vs Salvage Chemotx for Relapsed DLBCL

Event Free Survival

OverallSurvival

Transplantation

Conventional treatment

100

100

80

80

60

60

EFS (%)

OS (%)

40

40

20

20

P = .001

P = .038

0

0

0

15

30

45

60

75

90

0

15

30

45

60

75

90

Mos After Randomization

Mos After Randomization

Philip T, et al. N Engl J Med. 1995;333:1540

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