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![Page 1: Should peripheral T-cell lymphoma be treated by autologous ... · PDF fileShould peripheral T-cell lymphoma be treated by autologous or allogeneic SCT? ... Largest prospective PTCL](https://reader031.vdocument.in/reader031/viewer/2022030511/5abb04f17f8b9a8f058c083d/html5/thumbnails/1.jpg)
Francesco d’Amore, MD, PhD
Dept. Of Hematology
Aarhus University Hospital,
Aarhus, Denmark
Should peripheral T-cell lymphoma be treated by autologous or allogeneic SCT?
Disclosure of Interest: Nothing to Disclose
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Upfront ASCT in PTCL: Scenario with conventional CHOP/CHOP-like approach
31 clinical trials: tot 2815 pts ( period:1990-2010) Overall (all subtypes): 5 yr OS 38.5%
Abouyabi s et al, ISNR Hematology 2011
Meta-analysis of CHOP/CHOP-like outcome in PTCL
ALCL (overall) 56.5%
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Autotransplantation in PTCL (retrospective) – Salvage Treatment
Author n CR OS Comment
Vose (1990) 17 59% 35% (2y)
Fanin (1999) 64 n.d. 70% (5y) ALCL
Rodriguez (2001) 29 79% 39% (3y) subgroup
Blystad (2001) 40 80% 58% (3y)
Song (2003) 36 42% 48% (3y)
Rodriguez (2003) 78 68% 56% (5y) subgroup
Schetelig (2003) 15 67% 44% (5y) AIL, subgroup
Jagasia (2004) 28 50% 69% (3y) incl. CTCL
Jantunen (2004) 37 76% 54% (5y) subgroup
Kewalramani (2006) 24 n.d. 33% (5y)
Nademanee (2006) 57 n.d. 45% (2y) subgroup
Kim (2007) 40 n.d. 11.5m subgroup
Smith (2007) 32 n.d. 43% (3y) subgroup
Chen (2008) 53 79% 40% (5y) subgroup
Khouri (2008) 59 80% 43.5m subgroup
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Autotransplantation in PTCL (retrospective) - 1. Line Treatment
Author n Regimen CR OS Comment
Rodriguez (2007) 19 BEAM, BEAC, CVB,
Cy+TBI 79% 60% (5y) only AILT, subgroup
Rodriguez (2007) 74 BEAM, BEAC, CVB,
Cy+TBI n.d. 68% (5y) incl. ALCL
Feyler (2007) 64 misc n.d. 53% (3y) incl. ALK+ALCL
Kyriakou (2008) 146 misc 70% 59% (4y) only AILT, subgroup
Khouri (2008) 79 mainly BEAM n.d. 60% (5y) incl. ALCL, subgroup
Lee (2008) 47 misc n.d. 86% (5y DFS) only extranodal
PTCL
Yang (2009) 64 misc n.d. 53% (3y) only PTCLu
Nademanee A
(2011) 67 misc n.d. 54% (5y) 66 mo med follow-up
Prochazcha V (2011) 29 misc 66% 65% (2y) PTCL-NOS, alk-neg
ALCL, AILT, EATL
Iriyama N (2013) 28 Double CHOP>
Cy+Eto+Ranimustine 68% 63% (5y) Alk+ ALCL excluded
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HDT in PTCL-NOS Retrospective data from the International T-cell Project
p= 0.0076 p< 0.001
HD Therapy
yes
no
CENSOR FAIL TOTAL MEDIAN
21 27 48 3.5
63 148 211 1.95
Time
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10 12 14 16 18
Pro
po
rtio
n
Time
Pro
po
rtio
n
0.0
0.2
0.4
0.6
0.8
1.0
0 2 4 6 8 10
Transplantation CENSOR FAIL TOTAL MEDIAN
1. line 8 15 23 1.4
6 0 24 24 0.71 2. line
Overall survival Failure-free survival
Armitage, Vose, et al. J Clin Oncol (2008)
possibly an advantage and, if so, rather upfront
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Largest prospective PTCL trials with HDT in 1st line
Study Histology Type Design N of pts
(ITTP)
Med
follow-up
Accrual
status
Efficacy
(Ref)
Treatment naive PTCL
ACT sPTCL IIS phase 3 250 30 mo Ongoing ASH 2012
NLG-T-01 sPTCL IIS phase 2 160 60 mo Closed JCO 2012
Reimer et al sPTCL IIS phase 2 83 33 mo Closed JCO 2009
IIS = Investigator-initiated study
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Parameter
N pts 83
Schedule - CHOP-21 x 4-6
- Mobilizing DexaBEAM
- TBI+CY
Median follow-up 33 mo
5 yr OS
3 yr PFS
40%
36%
Progression-free survival
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60
Time (months)
(n=83)
Overall survival
0
0,2
0,4
0,6
0,8
1
0 12 24 36 48 60
Time (months)
(n=83)
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CHO(E)P-14d x 3
CHO(E)P-14d x 3
(stem cell collection)
HDT (BEAM)
Follow-up
Excluded:
• Precursor TCL
• alk+ ALCL
• CTCL
• Primary leukemic PTCL
CHO(E)P :
18-60 yrs: CHOEP-14 (n=118)
61-67 yrs: CHOP-14 (n=42)
CR, PR NC,PD
CR, PR NC,PD
JCO 2012;30(25):3093-9
60 mo median follow-up
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NLG-T-01: OS and PFS Median follow-up: 5 yrs (range 2-8 yrs)
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36 48 60 72months
160 113 96 76 59 46 17 Number at risk
95% CI Survivor function
OS, whole cohort
5-yr OS
51%
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36 48 60 72months
160 100 85 65 52 39 17 Number at risk
95% CI Survivor function
PFS, whole cohort
5-yr PFS
44%
Dose-dense induction followed by HDT/ASCT: is well tolerated leads to long-term PFS in 44% of pts best in alk-neg ALCL (5y PFS:61%; OS:70%) useful reference for future studies
N of evaluable patients: 160 Median age: 57 yrs
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ASCT 1st line in PTCL OS +PFS in the Nordic and German trial
OS Nordic
trial
German
trial
3-yrs 57% 48%
5-yrs 51% 40%
PFS Nordic
trial
German
trial
3-yrs 49% 36%
5-yrs 44% n.d.
Comparison of treatment schedules
Induction Conditioning
regimen
Nordic trial CHOEP-14 x6 BEAM
German trial CHOP-21 x4-6
+ DexaBEAM/ESHAP (mobilizing)
HdCy+TBI
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NLG-T-01: OS and PFS - largest subtypes
p=0.21 (logrank test)
0.0
0.4
0.2
0.6
0.8
1.0
0 12 24 36 48 60 72months
PTCL-NOS AILT
Alk-negative ALCL EATL
OS, largest subtypes
Median follow-up: 5 years
Histology 5-yr OS 95% CI
ALCL 70% 50%-83%
AILT 52% 33%-69%
EATL 48% 26%-67%
PTCL-NOS 47% 34%-59%
p=0.26 (logrank test)
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36 48 60 72months
PTCL-NOS AILT
Alk-negative ALCL EATL
PFS, largest subtypes
Histology 5-yr PFS 95% CI
ALCL 61% 42%-76%
AILT 49 % 30%-65%
EATL 38 % 18%-57%
PTCL-NOS 38 % 25%-50%
Meta-analysis CHOP 5y OS (Abouyaby, 2011)
56.5 %
36.5 %
21 %
34%
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Parameter Comment Values
N pts CHOP-like
IfosfVepEpi + MTX+ASCT
Ntot= 54
Ntot= 26
Data period CHOP-like
IfosfVepEpi + MTX+ASCT
1994-1998
1998-2009
Outcome
(historical comparison) 5 yr OS 22 vs 52%
Intensified induction + upfront ASCT in EATL Retrospective analysis of prospectively collected data
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Guidelines – ESMO + NCCN
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Improve induction
Improve consolidation/
consider maintenance
1st line treatment of PTCL Patterns of treatment failure
Diagnosis 2 yr est 5 yrs PFS = 44%
26%
18% 7%
3 yr End of induction,
consolidation
New trials
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HDT
CHOP-14
The ACT trial
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
HDT
R
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
CHOP-14
R
18 yrs
65 yrs
80 yrs
CHOP-14
CHOP-14
N=133 N=117 N=250
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Time-related end-points (not arm-specific)
Response rates
ACT-1 Response rates and time-related end-points
Response rates N (%)
ORR 42 (67)
CR/CRu 38 (61)
PR 4 (6)
SD 3 (5)
PD 16 (25)
Not evaluable 2 (3)
Total 63 (100)
Months
Pro
po
rtio
n
0 5 10 15 20 25 30 35 40 45 50
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
EFS
Months
Pro
po
rtio
n
0 5 10 15 20 25 30 35 40 45 50
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
PFS
Primary Secondary
End-point 1-yr (95% CI)
EFS 55% (42-67)
PFS 54% (42-67)
OS 78% (67-88)
15 mo median follow-up
d’Amore et al, ASH 2012 abs #57
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The ACT and NLG-T-01 trials Outcome “meta-analysis” with regard to ASCT
Auto
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
Auto
R
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
A30 - CHOP-14
CHOP-14
R
CHOP-14
CHOP-14
”Meta-analysis” Cohort Est. N
NLG-T-01 61-67 yrs (CHOP + HDT) 60-70
Std ACT-1 50-60 yrs (CHOP + HDT)
Std ACT-2 61-70 yrs (CHOP) 60-70
CHO(E)P-14
CHO(E)P-14
CHO(E)P-14
CHO(E)P-14
CHO(E)P-14
CHO(E)P-14
Auto
NLG-T-01 (>60y)
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18
Induction Consolidation Follow-up
1st yr
Follow-up
2nd yr
Follow-up
3rd yr
Follow-up
4th yr
Follow-up
5th yr
Follow-up
6th yr
Follow-up
7th yr
Follow-up Median 98 (63.9 – 133.8) months
Histology Early (<2yrs) post-therapeutic relapses Late (≥2yrs) post-therapeutic
relapses
N Time points for relapse (yrs) N Time points for relapse (yrs)
PTCL-NOS 8 0.2; 0.2; 0.3; 0.3; 0.5; 0.9; 1.3; 1.5 5 2.3; 3.6; 3.8; 3.9; 5.3
AILT 6 0.2; 0.3; 0.3; 0.5; 1.0; 1.5 3 2.8; 4.2; 6.1
ALCL (alk-) 6 0.2; 0.3; 0.3; 0.3; 0.3; 1.0 3 2.8; 5.0; 6.4
EATL 5 0.3; 0.4; 0.8; 0.8; 1.2 2 2.3; 7.1
SCPL 1 1.5 -
HSTCL 1 0.2 -
NLG-T-01: long-term follow-up (8 yr median)
d’Amore et al. 12th ICML Lugano 2013; abs # 238
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#155: Intensified chemo-immunotherapy for patients affected by nodal peripheral T-cell lymphomas (PTCLs) at diagnosis: Final results of a phase II multicentre prospective trial P. Corradini et al.
• Italian phase II study performed (NCT01679860)
A: 18-60 yrs: 2 x CHOP-21 + Campath (30 mg)
2 x Hyper-C-Hidam (Cy-AraC-Mtx)
Responding pts received auto-SCT or allo-SCT based on genetic stratification
B: 61-75 yrs: 6 x CHOP-21 + Campath (10 mg)
• Cohort of 86 pts (A: n=61; B: n=25) PTCL-NOS: 49%
AILT: 24%
ALCL Alk-neg: 22%
EATL: 5%
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P. Corradini et al.
A: 18-60 yrs B: 61-75 yrs
Median follow-up 40 mo 48 mo
Estimated 4yrs OS PFS DFS
48.8% (95% CI, 67.6-63.2%) 44.0% (95% CI, 33.1-58.5%) 79.0% (95% CI, 65.1-95.5%)
31.5% (95% CI, 17.6-56.5%) 26.7% (95% CI, 13.6-52.3%) 44.4% (95% CI, 24.6-80.5%)
NRM 13% (majority of pts belonged to the allo-SCT cohort) 12%
ORR at the end of induction
67% (CR 56%; PR 11%) -
Consolidation Auto-SCT: 14 pts (OS vs non-transpl:HR 0.04; p=0.004) Allo-SCT: 23 pts (OS vs non-transpl:HR 0.22; p=0.008) No consolidation: 23 (PD: 18 pts; toxic deaths: 5 pts) 1 pt maintained remission without consolidation
-
Multivariate analysis
(PFS, OS)
cCR for at least 6 mo: significant for both PFS and OS
Undergo transplantation: significant for OS
CONCLUSION: Upfront transplantation was associated with a prolonged DFS in younger patients. No outcome improvement for the chemoimmunotherapy treated elderly cohort
FINDINGS:
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Modality N pts Med age Histologies (N)
Auto 115 43 yrs ALCL: 53 PTCL-NOS: 34 AITL: 13
Allo 126 38 yrs ALCL: 51 PTCL-NOS: 63 AITL: 12
Total 241
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Auto vs Allo – PFS and OS (all pts) Auto vs Allo – NRM
RIC vs Myabl – NRM Auto vs Allo – PFS and OS (CR1 excl)
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Should SCT in 1st remission be the standard of care for patients with PTCL?
age >65-67yrs (45-50%)
alk+ALCL (no pediatric cases) (3%)
stage I low-risk non-bulk disease (2%)
severe co-morbidity (4%)
(only for alloSCT): no donor availability
For approximately 50-60% of them => no
Treatment setting Ptt. Description No. of ptt. in the cohort (%)
1st-line*
”young & fit”
(≤65 y & PS≤ 2)
241/470 (51)
“elderly & fit”
(> 65 y & PS≤ 2)
164/470 (35)
“Frail”
(PS>2)
65/470 (14)
Bjerregaard-Pedersen M – 12th ICML, abs #234, Ann Oncol Suppl 2013
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Should high-dose therapy with autologous stem cell support be recommended in 1st remission for the
40-50% transplant eligible patients with PTCL?
• yes, as it probably provides the possibility to improve the quality of remission and thereby the duration of respons
• Although no randomized clinical trials are presently available to answer the question in a definitive way
• And limited to
① transplant- and risk-eligible
② chemosensitive (CR, CRu, PR)
③ ’risk-eligible’ (i.e. stage I non-bulk, IPI 0-1 excluded)
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Should peripheral T-cell lymphoma be treated by auto or allogeneic SCT?
F. d’Amore
Aarhus University Hospital, Aarhus, Denmark
Berlin, October 2013
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NLG-T-01: Flow chart
160 pts
confirmed diagnosis
156 pts
Evaluable response
90 pts
CR/CRu 3 mo post Tx
115 pts
transplanted
131 pts
CR/PR after 6xCHOEP
4 pts not evaluable response
25 pts primary refractory
16 pts PD/tox/mobilisation
failure/other before Tx
25 pts PR/PD/tox
166 pts
enrolled
6 pts inclusion criteria not fulfilled
Flow chart of the NLG-T-01 study
cohort showing the number and types of
treatment failures and the responding
patients throughout the different stages
of the treatment algorithm.
ORR pre-Tx 131 (82%)
CR/CRu 82 (51%)
PR 49 (31%)
% Tx 115 (72%)
CR/CRu 100d post-Tx
90 (56%)
Intention-to-treat population
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NLG-T-01: CHOP vs ’elderly’ CHOEP
Median follow-up: 5 years
Subcohort 5yr OS 5yr PFS
55-60 yrs CHOEP (n=50) 40% 39%
60-67 yrs CHOP (n=42) 45% 34% 0.0
00.2
00.4
00.6
00.8
01.0
0
0 12 24 36 48 60 72analysis time
CHOEP CHOP
NLG-T01: OS for CHOP vs 'elderly' CHOEP, p=0.64
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0.0
00.2
00.4
00.6
00.8
01.0
0
0 12 24 36 48 60 72analysis time
alcl = Not ALCL alcl = ALCL
NLG-T01: OS - ALCL vs non-ALCL, p=0.026
NLG-T-01: OS and PFS – ALCL vs non-ALCL histology
Median follow-up: 5 years
0.0
00.2
00.4
00.6
00.8
01.0
0
0 12 24 36 48 60 72analysis time
alcl = Not ALCL alcl = ALCL
NLG-T01: PFS - ALCL vs non-ALCL, p=0.044
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NLG-T-01: ALCL vs non-ALCL
No difference in age, CS, IPI and BM involvement
Histology CS I-II N (%)
CS III-IV N (%)
p-value (Fisher’s exact)
ALCL 8 (26%) 23 (74%)
0.319
non-ALCL 23 (18%) 106 (82%)
Clinical stage Age
IPI
Histology IPI low N (%)
IPI int-high N (%)
p-value (Fisher’s exact)
ALCL 12 (39%) 19 (61%)
0.182
non-ALCL 33 (26%) 96 (74%)
Histology median (yrs)
Rank-sum (obs/exp)
p-value*
ALCL 53.8 yrs 10632/10385
0.285
non-ALCL 50.2 yrs 2248/2496
* Two-sample Wilcoxon rank-sum (Mann-Whitney) test
BM involvement
Histology No N (%)
Yes N (%)
p-value (Fisher’s exact)
ALCL 23 (74%) 8 (26%)
1.000
non-ALCL 96 (74%) 33(26%)
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NLG-T-01: Prognostic factors
Parameter OS PFS
HR CI 95% p-value HR CI 95% p-value
Univariate analysis
Female gender 0.54 0.32-0.92 0.023 0.58 0.36-0.94 0.027
Age (per year) 1.03 1.01-1.05 0.017 1.03 1.01-1.05 0.012
PS≥2 1.58 0.98-2.54 0.058 1.59 1.02-2.47 0.039
BM involvement 1.72 1.07-2.76 0.025 1.83 1.18-2.84 0.007
ALCL histology 0.46 0.23-0.92 0.029 0.54 0.29-0.99 0.048
Elevated s-LDH 1.31 0.82-2.10 0.26 1.23 0.80-1.90 0.35
CS III-IV 0.85 0.49-1.47 0.56 1.09 0.63-1.87 0.76
Multivariate analysis
ALCL histology 0.46 0.23-0.93 0.031 0.51 0.27-0.94 0.030
Age (per year) 1.03 1.00-1.05 0.041 1.03 1.00-1.05 0.028
PS≥2 1.66 1.02-2.71 0.041 1.69 1.08-2.67 0.023
Female gender 0.61 0.36-1.04 0.069 0.63 0.39-1.03 0.064
BM involvement 1.50 0.92-2.44 0.102 1.67 1.06-2.63 0.027
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Population-based clinicopathological features Danish Lymphoma Registry LYFO (2000-2010)
PTCL-NOS (n=218)
AITL (n=91)
ALK+ ALCL (n=49)
ALK- ALCL (n=89)
EATL (n=15)
All (n=462)
Med age (yrs) 65 68 41 61 62 63
M/F ratio 1.2 1.3 1.6 1.9 1.1 1.4
Stage III/IV (%) 70 95 61 53 47 70
PS (ECOG) (%)
0 I II III IV
42 29 15 8 6
27 34 19 12 8
42 36 9 4 9
46 34 10 2 8
40 46 7 7 0
40 32 14 7 7
>1 Exnod site (%) 22 15 24 18 20 20
BM involvement, % 32 43 10 11 0 27
Pedersen et al. 12th ICML Lugano 2013; abs # 234
• Approximately 49% of the pts were not eligible (e.g. high age, poor PS) for trials involving upfront SCT.
• Approximately 80% of pts were considered eligible for any interventional clinical trial (age, PS, co-
morbidity, unable to give informed consent etc).
• Of the potential 80% candidates (any trial), only 11% were actually included in a clinical trial emphasizing
the need of optimizing recruitment strategies and trial designs, particularly for the frailest subset of pts.
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HDT in PTCL – Summary and perspectives
• Did NLG-T-01 improve upon a comparable historical cohort?
• A characterization of long-term responders vs refractory and relapsing patients should be attempted Trial-specific TMA and nucleic acid analysis from FFPE samples
Protein analysis on frozen tissue samples and validation with WB and IH
NGS aCGH GEP miRNA
Work in progress…
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36 48 60 72months
160 113 96 76 59 46 17 Number at risk
95% CI Survivor function
OS, whole cohort
51%
Possibly
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NLG-T-01: Demographics
Pre-therapeutic clinico-
pathological patient
characteristics (N=160)
Characteristic No. of patients (%)
Age, yrs
- Median
- Range
57
22-67
Sex
- Male
- Female
107 (67)
53 (33)
B-symptoms 94 (59)
Elevated s-LDH 99 (62)
PS 2 46 (29)
Bulk 26 (17)
CS III-IV 129 (81)
BM involvement 41 (26)
IPI (2) 115 (72)
Histological subtype
- PTCL-NOS
- ALK-neg ALCL
- AILT
- EATL
- Panniculitis-like
- T/NK nasal type
- Hepatosplenic
62 (39)
31 (19)
30 (19)
21 (13)
6 (4)
5 (3)
5 (3)
PL HSL T/NK
EATL
ALCL
AILT NOS
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NLG-T-01: Toxicity and causes of death
Cause of
death
N pts % of
deceased
% of total
Lymphoma 54 75% 34%
Toxicity 7 10% 4%
2nd cancer 2 3% 1%
Other causes 6 8% 3%
Unknown 3 4% 2%
Total 72 100% 45%
Toxicity Gr.3-4
% of total
Hematological 65%
Non-hematological 45%
- Infection 37%
- Gastrointestinal 4%
- Mucositis 4%
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NLG-T-01: OS - rare subtypes Median follow-up: 5 years
0.0
0
0.2
0
0.4
0
0.6
0
0.8
0
1.0
0
0 12 24 36 48 60 72 analysis time
panniculitis-like (PL) Extranodal T/NK (T/NK)
Hepatosplenic (HS)
OS, rare subtypes
Histology 3-yr OS 95% CI
PL 50% 11%-80%
HS 40% 5%-75%
T/NK 40% 5%-75%
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0.0
0
0.2
0
0.4
0
0.6
0
0.8
0
1.0
0
0 12 24 36 48 60 72 analysis time
panniculitis-like (PL) extranodal T/NK (T/NK)
Hepatosplenic (HS)
PFS, rare subtypess
NLG-T-01: PFS - rare subtypes Median follow-up: 5 years
Histology 3-yr OS 95% CI
PL 50% 11%-80%
HS 40% 5%-75%
T/NK -- --
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Treatment group
SAE per patient
Before
amendment (n=8)
After
amendment (n=35)
6x CHOP-14 (n=21) 2/ 3 (0.67) 8/ 18 (0.44)
6x CHOP-14 + A (n=22) 13/ 5 (2.60) 13/ 17 (0.76)
Total (n=43) 15/8 (1.89) 21/ 35(0.60)
ACT-1 SAEs before and after the ALZ dose amendment
Blood 2011; 118:1755
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CTC
% pts
6 x
CHOP
6 x
CHOP - A all
Leukocytopenia
WHO= 4 29.4 71.0 50.0
Thrombocytopenia
WHO= 3, 4 18.8 17.6 18.2
Anemia
WHO= 3, 4 14.3 47.4 30.0
ACT-1 Feasibility
Haematological toxicity
6 x CHOP-14 median: 73
6 x CHOP-14 + A median: 81
Pro
po
rtio
n o
f p
ati
en
ts
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 10 20 30 40 50 60 70 80 90 100 Days
Schedule adherence
Type of
infection
6x
CHOP-14
6x
CHOP-14 + A
Bacterial 54.8% 45.9%
Fungal 6.5% 5.4%
Viral 29.0% 35.1%
Unknown 71.0% 75.7%
Infections
Parameter
6x
CHOP-14
6x
CHOP-14 + A p-
value
Median Median
N reinfused CD34+
cells (106)/ kg b.w. 3.9 3.9 0.4
Days to ANC
>0.5x109/l 11 11 0.6
Days to Platelets
>50x109/l 16 14 0.8
SC harvest and recovery
(Blood 2011; 118:1755)
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ACT-1 vs NLG-T-01
ORR and 1-year PFS/OS
The non arm-specific outcome of the ACT-1 trial is similar to the one of the NLG-T-01 trial for ORR, CR ,1-yr PFS and OS
ACT-1
(not arm-specific, no ALCL)
50% CHOP -14x6 50% A-CHOP-14 x6
NLG-T-01
(without ALCL)
CHOEP-14 x6 +ASCT
ORR % 67 64
CR-CRu (%) 61 56
1-yr PFS (%) 54.4
(95% CI: 42;67)
57,5
(95% CI: 50; 65)
1-yr OS (%) 77.6
(95% CI: 67;88)
68,3
(95% CI: 61; 75)
+ ASCT
d’Amore et al, ASH 2012 abs #57
15 mo median follow-up
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Efficacy of Alemtuzumab in combination with dose-
adjusted EPOCH in untreated nodal PTCL
Grant C et al ASCO 2012, Abstr.8051
Nodal PTCL
ATLL P=0.06 ATLL
Nodal PTCL
P=0.08
45 mo median follow-up Jiang
BJH 2009
Geissinger
L& L
2009
PTCL-NOS 93% 90 %
AILT 100% 90%
ALCL --- 0%
HS 100%
T/NK 25%
CD52 expression
Prior dose-finding Phase I study (Janik et al, ASH 2007) ►► 30 mg pr course of daEPOCH
Courtesy of dr. Cliona Grant (adapted)
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HDT in PTCL – some statements
• HDT with ASCR ’per se’ does probably not make a major difference in PTCL
• Retrospective and prospective data favour the use of HDT as part of a dose-dense induction/consolidation strategy in chemosensitive patients in the upfront setting
• On the basis of the experience from the first large PTCL-restricted prospective trials a heterogeneity of responses should be acknowledged with regard to specific subtypes and to individual patients within the single subtypes
Improve induction Consolidate response Maintain response
Diagnosis 1 yr 5 yrs PFS
25-35%
15-25% 5-10%
3 yr SCT
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Autotransplantation in PTCL - 1. Line Treatment
Prospective PTCL-restricted trials
N pts Age Regimen Tx rate
(%) CR/PR (%) TRM (%) OS FU
Corradini
(Leukemia 2006)
62 (inkl.alk+
ALCL) 43
1.APO>DHAP>HDMito/Mel 2. MACOP-B> hdAraC/ Mito> BEAM
74 72 4.8
34% (12 y)
76 mo
Rodriguez
(EJH2006) 26 44 MegaCHOP/IFE 73 81 0 73% (3y) 35 mo
Mercadal
(Ann Oncol 2008)
41 47 HighCHOP/ESHAP altern. > BEAM/BEAC
41 59 n.d. 39% (4y) 3.2 y
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Aims of NLG-T-01
• To provide a PTCL-restricted prospective trial with a cohort of sufficient size to perform subtype analysis N=160
• To provide a cohort with a risk-profile as close as possible to the spectrum of transplant-eligible patients seen in daily clinical practice Median age: 57yrs; IPI≥2 : 72%
• To provide a follow-up of sufficient length to allow an appropriate estimate of both early and late failures Median follow-up: 5 years;
Report of 9-yrs median follow-up analysis planned for 2014
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HDT in PTCL – some statements
• HDT with ASCR ’per se’ does probably not make a major difference in PTCL
• If at all, retrospective and prospective data seem to favour the use of HDT as part of a dose-dense induction + consolidation strategy in chemosensitive patients in the upfront setting
• On the basis of the experience from the first large PTCL-restricted prospective trials a heterogeneity of responses should be acknowledged with regard to specific subtypes and to individual patients within the single subtypes (trial-specific correlative biological studies are warranted to biologically differentiate responders form non-responders)