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

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%

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

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

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

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

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)

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

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

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

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%

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

Guidelines – ESMO + NCCN

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

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

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

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)

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

#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%

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:

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

Auto vs Allo – PFS and OS (all pts) Auto vs Allo – NRM

RIC vs Myabl – NRM Auto vs Allo – PFS and OS (CR1 excl)

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

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)

Should peripheral T-cell lymphoma be treated by auto or allogeneic SCT?

F. d’Amore

Aarhus University Hospital, Aarhus, Denmark

Berlin, October 2013

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

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

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

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%)

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

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.

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

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

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%

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%

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 -- --

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

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)

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

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)

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

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

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

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)