Transplantation in Lymphoma

Dr Adrian BloorTransplant Director

The Christie NHS Foundation Trust

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Are you a believer?

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Transplant Outcomes

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Summary

• A big subject in 20 mins

• Briefly review rationale for transplantation

• Autografting Historical results and place in current treatment

New data in DLBCL, MCL

• Allografting Follicular NHL

Hodgkin Lymphoma

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Autologous Transplantation

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Dose intensity

Cou

nt

Time

Blood countDisease

Cou

nt

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Autologous Transplantation

Indication TrialMedian PFS

months

OS

months

Relapsed FL CUP >36 vs 12 NR vs 46

Transformed FL EBMT NS (vs controls) NS (vs controls)

MCL MCL Network 39 vs 17 NS

Relapsed DLBCL PARMA >48 vs <12 NR vs 15

Relapsed HL BNLI/GHDSG >36 vs <12 NS

Williams CD et al J Clin Oncol 2001;19:727Shouten HC et al J Clin Oncol 2003;21:3918Dreyling M et al Blood 2005;105:2677Philip T et al N Engl J Med 1995;333:1540Schmitz N et al Lancet 2002;359:2065Linch DC et al Lancet 1993;341:8852

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CORAL - DLBCL

Gisselbrecht C et al J Clin Oncol 2009;27:8509a

n = 396• Response rate 63% • Relapse < 12 months (46% vs 88%) • Prior Rituxumab (51% vs 83%)

Relapsed DLBCL

R-ICE

R-DHAP

BEAM

RANDOMISE

Observe

R maint

RANDOMISE

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CORAL - DLBCL

n = 123

3 year OS/EFS 47/30%

PET –ve

OS 66%EFS 40%

Trneny M et al Blood 2009;114:881a

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CORAL - DLBCL

n = 123

3 year OS/EFS 47/30%

PET –ve

OS 66%EFS 40%

PET +ve

OS 49%EFS 16%

p = sig

Trneny M et al Blood 2009;114:881a

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Mantle Cell Lymphoma - Nordic

n = 41

ORR 75% CR 27%

4 yr PFS 15%

n = 160

ORR 96% CR 54%

6 yr PFS 66%

NRM 5%

Z-BEAM (no CR)

MCL 32006-2009

n = 160

ORR 96% CR 68%

NRM 4%

maxi-CHOPx4

BEAM(C) auto

MCL 11996-2000

R-maxi-CHOP /R-HD-AraC x6

Purged BEAM(C) auto

R

MCL 22000-2006

Andersen NC et al Eur J Haematol 2003;71:73 Geisler CH et al Blood 2008;112:2687 Kolstad A et al Blood 2009;114:932a

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Autograft mortality 1998-2002

SUM05_20.ppt

Infection (6%)

Other (9%)

Organ toxicity (8%)Relapse (75%)

Unknown (2%)

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Allogeneic Transplantation

derived from Bortin MM Transplantation 1970;9:571

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Beneficial effect of GvHD

Horowitz MM et al Blood 1990;75:555

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RECIPIENT DONOR

GvD

GvHD and GvDisease

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RECIPIENT DONOR

GvD

GvHD and GvDisease

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GvHD and GvDisease

0.00001

0.0001

0.001

0.01

0.1

1

Jun-09 Sep-09 Dec-09 Mar-10 Jun-10 Sep-10

Chemo SCT

CSA

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Follicular NHL

Series Follow up n Protocol PFS/OS NRMExtensive

cGvHD

UCLH 43 mo 82 FMC90% (sib)

64% (UD)

8% (sib)

22% (UD)18%

MDACC 60 mo 43 FCR 85% 16% 36%

Thomson KJ et al J Clin Oncol 2010;28:3695Khouri IF et al Blood 2008;111:5530

Montoto S et al Leukemia 2007;21:2324

Replacement for autograft?

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HL: Winners and Losers

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HL: Salvage autografts

Schmitz N et al Lancet 2002;359:2065Linch DC et al Lancet 1993;341:8852

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MSKCC

• 71 patients (1994-2005)• Poor prognosis• Second transplant improves

outcome

And if it doesn’t work?

Moskowitz AJ Br J Haematol 2009;146:158

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AlloHSCT for poor prognosis?

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AlloHSCT for poor prognosis?

Milied N et al J Clin Oncol 1996;14:1291

EMBT matched pair series

• 90 patients• >50% refractory relapse• 2 yr NRM >50% (allo) vs 12% (auto)

But..

• GvHD appears beneficial• Relapse rate 13% (allo) vs 69% (auto)

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RIC Allo outcome

Centre nPrior HDT

RefractoryPFS

(2-4 yr)

OS

(2-4 yr)

EBMT 401 67% 22% 26% (3 yr) 41% (3yr)

Single Centre

32-5871-

100%33-50% 8-39% 32-64%

NRM 12-46% Age, PS, date of transplant

Robinson SP et al Haematologica 2009;94:230

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Pick a winner

TTF – based on prognostic score

• PS• Disease Status• Chemosensitivity• Remission duration• Tumour bulk • Extranodal disease

eg Stanford series

Johnston LJ et al Biol Blood Marrow Trans 2000;6:289

0

1

32

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Pick a winner

Patient A Patient B

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Risk Stratification by FI

Centre n Technique3 yr EFS

PET +ve

3 yr EFS

PET -ve

MDACC 21168 PET 174 Ga

27%52% (PR)

77% (CR)

MSKCC 16050 PET 110 Ga

33% 74%

Jabbour E et al Cancer 2007;109:2481Moskowitz C unpublished

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Trials

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Trials designed

ReACH

• Chemosensitive PET +ve second remission

• Siblings donors

PAIReD

• Chemorefractory (PET) first or second remission

• Matched donors

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Patient Selection

Extermann M et al Eur J Can 2000;36:453Havlik R et al Cancer 1994;74(s7):2101http://seer.cancer.gov/

Comorbidities by age

0

20

40

60

80

100

55-64 65-74 75+

Age range / yearsF

requ

ency

/ %

≤1 2-4 ≥5

0

100

0 20 40 60 80Age

Inci

denc

e / 1

00,0

00

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Conclusions

• A big subject in 20 mins

• Autologous transplant effective treatment for many patients with relapsed disease

• Autografts have no potential for cure

• Allogeneic effect exists in lymphoma

• Allogeneic transplantation remains developmental in most areas

• Ongoing trials in progress

• Patient selection essential – but how?