Seite 1 23. Januar 2007
Periphere T-Zell Lymphome
Wien, 13.10.2008
Gerald Wulf
14%
11% 18%
23%
6%12%7%
1%2%
2%5%
PTCL-U AILT NK/TALK+ ALCL ALK - ALCL ATLLETTL Cut ALCL HSTCLSCPTCL Other/Unclass
Biologie systemischer T-NHL: Heterogenität und Epidemiologie
Armitage et al. JCO 2008
Geissinger et al. J Path 2006
Expressionsprofil von PTCL: Assoziation mit maturen T-Zelltypen
AILT
Martinez-Delgado Hemtol Oncol 2006
Genexpressionsprofil von PTCL
Piccalagua et al. JCI 2007
Piccalagua et al. JCI 2007
Genexpressionprofil von PTCL: Identifikation von Zielstrukturen
Gisselbrecht et al. Blood 1998
Prognose des anaplastisch großzelligen Lymphoms
Anaplastisch großzelliges Lymphom: Bedeutung von ALK-Positivität
Savage et al. Blood 2008
FFS OS
Prognose des kutanen anaplastisch großzelligen T-Zell Lymphoms
Savage et al. Blood 2008
Bekkenk et al. Blood 2002
kutanes ALCL versus lymphomatoide Papulose
Savage et al. Blood Reviews2007
Bekkenk et al. Blood 2002
Gallamini et al. Blood. 2004
IPIAge, PS, LDH, ES, stage
PITAge, PS, LDH, BM
Prognose systemischer T-NHL: klinische Faktoren
addition of humoral immunotherapy :consolidation/maintenancealemtuzumab
dose escalation:HD therapy / autologous tx
MegaCHOEP
addition of humoral immunotherapy:alemtuzumab
addition of cellular immunotherapy: allogeneic SC transplantation
DHAP
FBC12
6 x CHOP146-8 x CHO/E/P14
TBICy
DexaBEAM
novel agents:antibodiessmall compounds
PTCL: approaches to improved treatment efficacy
Standard chemotherapy in PTCL: anthracycline-based ?
PTCL NOS AILT
Armitage et al. JCO 2008
Weidmann
(Germany)
Gallamini
(Italy)
Porcu
(USA)
Janik
(USA)HOVON
(NL)
Furman
(USA)
Trümper
(Germany)
Target group
PTCL
excl: alk+ALCL
PTCL
excl. alk+ALCL
PTCL
Incl. alk+ ALCL, ATLL, PTLD, CTCL,
LGL
PTCL
CD52-positive,
ATLL
PTCL,
excl: all ALCL,
hepatospl.
EATLwithout measurable
disease
PTCL
Probably incl. alk+ALCL
PTCL
excl. alk+ALCL
CT regimen
FCD CHOP 21 x8
CHOP-21 x8
EPOCH CHOP-14 x8
CHOP-21 x6
CHO(E)P-14 x6
Camp
timing
INDUCTION INDUCTION INDUCTION INDUCTION INDUCTION INDUCTION CONSOLID.
Dose esc.
Yes Yes Yes Yes Yes No Yes
Camp Total dose
292 mg 180-300 mg
77-293 mg 180-540 mg
673 mg 435-495 mg 180 mg
Cam route
i.v. s.c. s.c. i.v. s.c. s.c. i.v.
No pts 33 20 8 10 17 2 37
Periphere T-Zell Lymphome (PTCL): CX + Alemtuzumab
8x CHOP-21 + Alemtuzumab
OS PFS
Gallamini et al. Blood 2007
DSHNHL Trial 2003-1
CR / PRno infection
peripheral T-NHL
18 – 60 years:
6 x CHOEP-14+ Peg-F
Alemtuzumab-consolidation
133 mg in / 4 wks
36 Gy Bulk/E RTx
60 – 70 years:
6 x CHOP-14+ Peg-F
DSHNHL 2003-1: phase II alemtuzumab consolidation in PTCL
DSHNHL 30.07.07
Therapy arm
EFS OS
2 - years rate 95% CI 2 - years rate 95% CI
≤ 60 years(n=27)
38.1%[14.0%; 62.2%]
63.5%[40.8%; 86.2%]
> 60 years(n=14)
22.9% [ 0.0%; 48.0%] 55.0%[28.1%; 81.9%]
total(n=41)
32.0%[14.2%; 49.8%]
61.0%[43.6%; 78.4%]
with MabCampath (n=29)
43.9%[20.8%; 67.0%]
73.6%[54.6%; 92.6%]
DSHNHL Trial 2003-1
DSHNHL 2003-1: treatment outcome (ITT)
1days
15 29 43
R
71
CHOP
CHOP
CHOP
CHOP
CHOP
CHOP
57
S C
RE
BI PT C
BII
C C C C
RE F Dprogress : F death :
T-cell lymphoma
61-80 yearseligible for chemotherapyall stages, except stage I IPI 0 w/o bulk
documentation
forms :
CHOP + Alemtuzumab phase III: DSHNHL 2006-1B / ACT-2
CHOP
CHOP
CHOP
CHOP
CHOP
CHOP
A AA AAA
EBV-associated secondary NHL post CHOP w alemtuzumab
n = 20, HOVON 69 trial, 8x CHOP-21 w 8x 90 mg alemtuzumabKluin-Nelemans et al. Blood 2008: 02-138800
EBV associated secondary NHL post CHOP w alemtuzumab
HOVON 69 GITIL-trial ACT-2 DSHNHL 2003-1
CX 8x CHOP-21 8x CHOP-28 6x CHOP-14 6x CHO(E)P-14
alemtuzumab 720 240 (n=20) 360 133cumulative 120 (n=4)
time of cx 24 32 12 12 / 4[weeks]
observation 24+ 11 (5-42) 24+[months]
n 20 24 41 / 29
EBV-associated 3 0 0sec. NHL
Author (year)
n Regimen Response OS Histology
Gisselbrecht (2002)
4333
BEAM + ASCTACVBP
No data32% (5-year )39% (5-year)
ALCL : 29 (ALK unknown)PTCL: 55 (12 LBL)
Corradini (2006)
62Mito/Mel or BEAM
74%CR/PR
34% (12-year )ALCL: 19 PTCL-U: 28
Mercadal (2006)
41HighCHOP/ESHAP
60% CR/PR
39% (4-year ) No ALK+ ALCL
D´Amore (2006)
129 BEAM na 67% (3-year ) No ALK+ ALCL
Rodriguez (2007)
26MegaCHOP+/-IFE
73% CR/PR
73% (3-year ) No ALK+ ALCL
Reimer(ASH 2005)
65 Cy/TBI69% CR/PR
50% (3-year ) No ALK+ ALCL
Hochdosistherapie und autologe SZT bei PTCL
100% 65-75% 35…%
primärrefraktär
sekundärrefraktär
stabileRemission
Dx HDT 3yEFS
HD Therapie bei PTCL phase II: Probleme
Years
Ev
en
t fr
ee
su
rviv
al
(%)
0 1 2 3 4 5 6
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
DSHNHL 08.03.07
1.5 year rate 95%CI
total 31 % (16%;46%)
3 year rate
24 % (9%;38%)
n=36
HD Therapie bei PTCL phase II: MegaCHOEP II / III
1days 15 29 43
FBC
CHOP
CHOP
CHOP
CHOP
DHAP
BE AM
R
first-line treatment of mature (peripheral) T-cell lymphoma (PTCL), patients 60 years
inclusion criteria
• Peripheral T-cell lymphoma, unspec’d (PTCLu)• Angioimmunoblastic T-cell lymphoma (AIL)• Anaplastic large cell lymphoma, ALK negative• Extranodal NK/T-cell lymphoma, nasal type• Enteropathy type T-cell lymphoma• Hepatosplenic T-cell lymphoma• Subcutaneous panniculitis type T-cell lymphoma
• all stages and IPI except stage I with aaIPI 0
CR, PR, NC
R = At diagnosis, patients are randomized to allogeneic or autologous transplantation. Donor search (family or unrelated) will beinitiated only in patients randomized to allogeneic transplantation. Patients randomized to allogeneic tx but without a donor will receive autologous tx. Peripheral blood stem cells are harvested after DHAP in patients who are to receive autologous tx(randomized or crossed over from the allogeneic transplant arm because no donor is available).
ASCT = autologous stem cell transplantation, SCT = allogeneic stem cell transplantation
SCT
ASCT
CHOP
CHOP
CHOP
CHOP
DHAP
CR, PR, NC
64 |––-–– 4 - 6 weeks –-–––|
HD Therapie bei PTCL phase II: autologe versus allogene SZT
Allogene SZT bei rezidiviertem aggressiven NHL: konv. Konditionierung
Sung-Won et al. Blood 2006
n=111
PTCL im Rezidiv: allogene SCT nach Dosis-reduzierter Konditionierung
Corradini et al. JCO 2004
n=17
allogeneic SCT in relapsed PTCL: Göttingen experience
indication: relapsed peripheral T-cell lymphoma, chemosensitive
conditioning: fludarabin/busulfan (12 mg/kg bw)/cyclophosphamide
n: 20
OS: 11/20, median observation 4 months (range 1-47 months)
early death (TRM100): 3 / 20
late death (relapse): 3 / 20
late death (non-relapse): 3 / 20
agent target indication ORR author [%]
Gemcitabine nucleosid PTCL 60 Sallah 2001AraG 506U78 analoga PTCL 14 Czucsman 2004 a
Denileukin Il-2R PTCL 50 Dang 2004 aDifitox
Depsipeptide HDAc PTCL 26 Piekarz 2005aSAHA
SGN30 CD30 ALCL 33 Forero-Torres 2004a
Zanolimumab (CD4), Daclizumab (Il-2R), Bevacizumab
Sorafenib (TKI), Thalidomide (IMID), Bortezomib (proteasome)
novel substances
Zusammenfassung PTCL
heterogene Gruppe von histologisch, immunologisch und nach
Expressionsprofil klassifizierbaren Typen
ALK pos. ALCL: unter Anthracyclin-haltige Chemotherapie gute Prognose,
ansonsten Ergebnisse der konventionellen Therapie unbefriedigend
Primärtherapie
in Studien Evaluation von Alemtuzumab (DSHNHL 20061B, ACT-2)
HD-Therapie mit autologer bzw. allogener Stammzelltransplantation
(DSHNHL 2006-1A)
Sekundärtherapie
allogene SZT (DSHNHL 2003-R4); innovative, zielgerichtete Therapien (Studien)
Vielen Dank
DSHNHL
Kompetenznetz maligne Lymphome
Ihnen für Ihre Aufmerksamkeit
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