Periphere T-Zell Lymphome

Präsentation zum Thema: "Periphere T-Zell Lymphome"—  Präsentation transkript:

1 Periphere T-Zell Lymphome
Wien, Gerald Wulf 23. Januar 2007

2 Biologie systemischer T-NHL: Heterogenität und Epidemiologie
14% 11% 18% 23% 6% 12% 7% 1% 2% 5% PTCL-U AILT NK/T ALK+ ALCL ALK - ALCL ATLL ETTL Cut ALCL HSTCL SCPTCL Other/Unclass Armitage et al. JCO 2008

3 Expressionsprofil von PTCL: Assoziation mit maturen T-Zelltypen
AILT Geissinger et al. J Path 2006

4 Genexpressionsprofil von PTCL
Piccalagua et al. JCI 2007 Martinez-Delgado Hemtol Oncol 2006

5 Genexpressionprofil von PTCL: Identifikation von Zielstrukturen
Piccalagua et al. JCI 2007

6 Prognose des anaplastisch großzelligen Lymphoms
Gisselbrecht et al. Blood 1998

7 Anaplastisch großzelliges Lymphom: Bedeutung von ALK-Positivität
FFS OS Savage et al. Blood 2008

8 Prognose des kutanen anaplastisch großzelligen T-Zell Lymphoms
Bekkenk et al. Blood 2002 Savage et al. Blood 2008

9 kutanes ALCL versus lymphomatoide Papulose
Bekkenk et al. Blood 2002 Savage et al. Blood Reviews2007

10 IPI PIT Prognose systemischer T-NHL: klinische Faktoren
Age, PS, LDH, ES, stage PIT Age, PS, LDH, BM Other studies have found no distinction between patients with 2 or more factors Gallamini et al. Blood. 2004

11 PTCL: approaches to improved treatment efficacy
6 x CHOP14 addition of humoral immunotherapy : consolidation/maintenance alemtuzumab 6-8 x CHO/E/P14 addition of humoral immunotherapy: alemtuzumab addition of cellular immunotherapy: allogeneic SC transplantation DHAP FBC12 dose escalation: HD therapy / autologous tx novel agents: antibodies small compounds Mega CHOEP Dexa BEAM TBI Cy

12 Standard chemotherapy in PTCL: anthracycline-based ?
PTCL NOS AILT Armitage et al. JCO 2008

13 Periphere T-Zell Lymphome (PTCL): CX + Alemtuzumab
Weidmann (Germany) Gallamini (Italy) Porcu (USA) Janik HOVON (NL) Furman Trümper Target group PTCL excl: alk+ALCL excl. alk+ALCL Incl. alk+ ALCL, ATLL, PTLD, CTCL, LGL CD52-positive, ATLL PTCL, excl: all ALCL, hepatospl. EATLwithout measurable disease Probably incl. 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 CONSOLID. Dose esc. Yes No Camp Total dose 292 mg mg mg mg 673 mg mg 180 mg Cam route i.v. s.c. No pts 33 20 8 10 17 2 37 13

14 8x CHOP-21 + Alemtuzumab OS PFS Gallamini et al. Blood 2007

15 DSHNHL Trial 2003-1 peripheral T-NHL 6 x CHOEP-14 + Peg-F 6 x CHOP-14
DSHNHL : phase II alemtuzumab consolidation in PTCL DSHNHL Trial peripheral T-NHL 18 – 60 years: 6 x CHOEP-14 + Peg-F 60 – 70 years: 6 x CHOP-14 + Peg-F CR / PR no infection Alemtuzumab- consolidation 133 mg in / 4 wks 36 Gy Bulk/E RTx

16 DSHNHL Trial 2003-1 DSHNHL 2003-1: treatment outcome (ITT) Therapy arm
EFS OS 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

17 CHOP + Alemtuzumab phase III: DSHNHL 2006-1B / ACT-2
documentation BII RE forms : progress : F RE F death : D S BI PT C C C C C C C H O P T-cell lymphoma 61-80 years eligible for chemotherapy all stages, except stage I IPI 0 w/o bulk R A A A A A A C H O P days 1 15 29 43 57 71

18 EBV-associated secondary NHL post CHOP w alemtuzumab
case primary secondary interval post outcome histology histology alemtuzumab m, 41y PTCL NOS EBV + (endoth.) 10 months refractory to CT, CD2+,3+,5+ death recurr. EBV – f, 32y PLTCL EBV+, CD20+ - cerebral mass months RX cerv. DLBCL 12 months RX, rituximab cut. ind B-NHL 21 months PLTCL months alive m, 59y AILT EBV+, CD months early death B-lymphoprol. AILT n = 20, HOVON 69 trial, 8x CHOP-21 w 8x 90 mg alemtuzumab Kluin-Nelemans et al. Blood 2008:

19 EBV associated secondary NHL post CHOP w alemtuzumab
HOVON 69 GITIL-trial ACT DSHNHL CX 8x CHOP-21 8x CHOP-28 6x CHOP-14 6x CHO(E)P-14 alemtuzumab (n=20) cumulative (n=4) time of cx / 4 [weeks] observation (5-42) [months] n / 29 EBV-associated sec. NHL

20 Hochdosistherapie und autologe SZT bei PTCL
Author (year) n Regimen Response OS Histology Gisselbrecht (2002) 43 33 BEAM + ASCT ACVBP No data 32% (5-year ) 39% (5-year) ALCL : 29 (ALK unknown) PTCL: 55 (12 LBL) Corradini (2006) 62 Mito/Mel or BEAM 74% CR/PR 34% (12-year ) ALCL: 19 PTCL-U: 28 Mercadal 41 HighCHOP/ESHAP 60% CR/PR 39% (4-year ) No ALK+ ALCL D´Amore 129 BEAM na 67% (3-year ) Rodriguez (2007) 26 MegaCHOP+/-IFE 73% CR/PR 73% (3-year ) Reimer (ASH 2005) 65 Cy/TBI 69% CR/PR 50% (3-year )

21 HD Therapie bei PTCL phase II: Probleme
primär refraktär sekundär refraktär stabile Remission 100% 65-75% 35…% Dx 3yEFS HDT

22 HD Therapie bei PTCL phase II: MegaCHOEP II / III
n=36 1.5 year rate 95%CI total 31 % (16%;46%) 3 year rate 24 % (9%;38%) DSHNHL

23 HD Therapie bei PTCL phase II: autologe versus allogene SZT

24 Allogene SZT bei rezidiviertem aggressiven NHL: konv. Konditionierung
Sung-Won et al. Blood 2006

25 PTCL im Rezidiv: allogene SCT nach Dosis-reduzierter Konditionierung
Corradini et al. JCO 2004

26 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

27 agent target indication ORR author [%]
novel substances agent target indication ORR author [%] Gemcitabine nucleosid PTCL 60 Sallah 2001 AraG 506U78 analoga PTCL 14 Czucsman 2004 a Denileukin Il-2R PTCL 50 Dang 2004 a Difitox Depsipeptide HDAc PTCL 26 Piekarz 2005a SAHA SGN30 CD30 ALCL 33 Forero-Torres 2004a Zanolimumab (CD4), Daclizumab (Il-2R), Bevacizumab Sorafenib (TKI), Thalidomide (IMID), Bortezomib (proteasome)

28 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 A) Sekundärtherapie allogene SZT (DSHNHL 2003-R4); innovative, zielgerichtete Therapien (Studien)

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