How I treat the peripheral T-cell lymphomas - portal.ebmt.org · d'Amore F et al. JCO 2012;30:3093-3099 . Allogeneic transplantation as part of first-line therapy . AlloSCT in newly

How I treat the peripheral T-cell

lymphomas

Heidelberg, 25.09.2015

Norbert Schmitz

Hematology, Oncology and Stem Cell Transplantation

Asklepios Hospital St. Georg, Hamburg

Mature T- and NK-cell disorders Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Eds.):

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon 2008

Peripheral T-cell lymphoma, NOS

Angioimmunoblastic T-cell lymphoma

Anaplastic large cell lymphome (ALCL), ALK negative

Anaplastic large cell lymphome (ALCL), ALK positive

Extranodal NK-/T-cell lymphoma, nasal type

Enteropathy-associated T-cell lymphoma

Hepatosplenic T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma

T-cell prolymphocytic leukaemia

T-cell large granular lymphocytic leukaemia

Chronic lymphoproliferative disorders of NK-cells

Aggressive NK-cell leukaemia

EBV-positive T-cell lymphoproliferative disorders of childhood

Adult T-cell leukaemia/lymphoma

Mucosis fungoides

Sézary syndrome

Primary cutaneous CD30-positive T-cell lymphoproliferative disorders

Primary cutaneous gamma-delta T-cell lymphomas

















Mucosis fungoides

Sézary syndrome



















Mucosis fungoides

Sézary syndrome



T-cell lymphomas in DSHNHL trials

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Pro

po

rtio

n

0 10 20 30 40 50 60 70 80 90 100 110

Months

1: ALK+ (n= 73)

2: ALK- (n= 108)

3: PTCL (n= 68)

4: AILT (n= 28)

5: T/NK (n= 18)

p-values:

2 3 4 5

1 <0.001 <0.001 0.001 <0.001

2 0.350 0.958 0.339

3 0.537 0.700

4 0.472

Schmitz et al., Blood 2010;116(18):3418

ALK+ 88.8% (95% CI: 80.8%-96.8%)

ALK- 63.3% (95% CI: 53.9%-72.7%)

3-years OS-rate:

PTCL 52.9% (95% CI: 40.2%-65.6%)

AILT 65.9% (95% CI: 47.7%-84.1%)

T/NK 48.9% (95% CI: 25.4%-72.4%)

OS - histological subtypes (n=295)

DSHNHL

T-cell lymphomas in the Swedish Lymphoma Registry

OS - histological subtypes

ALK+ ALCL

ALK- ALCL

ALKu ALCL

PTCL NOS AITL

TCLu

Ellin et al., Blood 2014; 124:1570-77


DSHNHL

OS - International Prognostic Index (IPI) for all patients

(n=320)

IPI 0

(n=93)

IPI 1

(n=70)

IPI 2

(n=80)

IPI 3

(n=48)

IPI 4

(n=25)

IPI 5

(n=4)

0 10 20 30 40 50 60 70 80 90 100 110

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Pro

po

rtio

n

3-years OS-rate:

IPI 0: 82.0% (95% CI: 74.0-90.0%)

IPI 1: 72.7% (95% CI: 61.3-84.1%)

IPI 2: 60.7% (95% CI: 49.5-71.9%)

IPI 3: 49.8% (95% CI: 35.1-64.5%)

IPI 4: 26.7% (95% CI: 8.9-44.5%)

IPI 5: 25.0% (95% CI: 0.0-67.5%)

Months

Treatment Strategies in

Peripheral T-cell Lymphoma First-Line Therapy

CHO(E)P

High-dose therapy/autologous Tx

HDT

A

S

C

T

CHO(E)P

%

0

10

20

30

40

50

60

70

80

90

100

Months

0 10 20 30 40 50 60 70 80 90 100 110

p=0.057

without Etoposide (n=29)

with Etoposide (n=69)

Patients with other major subtypes GERMAN HIGH-GRADE NHL

STUDY GROUP (DSHNHL) www.lymphome.de/en/Groups/DSHNHL


Gemcitabine in PTCL

Study Regimen N ORR

Sallah et al

Br J Haematol. 2001 Gemcitabine monotherapy 10 60%

Zinzani et al

Phase II

Ann Oncol. 2010

Gemcitabine monotherapy 39 69%

Royal Marsden

Phase II

Arkenau. Haematologica

2007

GEM-P 16 69%

Spencer et al

Pilot study

Intern Med J. 2007

VGF 10 70%

Kim et al

Pilot study

Cancer Chemother

Pharmacol. 2006

CHOP-EG 26 77%

CHOP-EG=CHOP-etoposide, gemcitabine; GEM-P=gemcitabine, cisplatin, methylprednisolone;

VGF=vinorelbine, gemcitabine, filgrastim.

Courtesy Dr. Advani

Autologous transplantation

for consolidation after 1st-line therapy

No randomized study done!

HDT / autoSCT as part of 1st-line therapy in

PTCL:Prospective trials

Patients (n)

Age (years)

Regimen

Tx-rate (%)

ORR (%)

TRM (%)

OS F/U

Corradini Leukemia 2006

62 43

1. APO → DHAP →

HD Mito./Mel

2. MACOP-B →

HD AraC/Mito →

BEAM

74 72 4.8 34% (12 y) 76 mo

Rodriguez Eur J Haematol 2006

26 44

MegaCHOP/IFE

→ BEAM

73 81 0 73% (3y) 35 mo

Mercadal Ann Oncol 2008

41

47

HighCHOP/

ESHAP altern. →

BEAM/BEAC

41 59 n.d. 39% (4 y) 3.2 y

Reimer J Clin Oncol 2009

83 47

CHOP →

DexaBEAM/ESHAP

→ HD Cy + TBI

66 71 3.6 48% (3 y) 33 mo

D`Amore J Clin Oncol 2012

160 57

CHOEP-14

→ BEAM

72 82 4 51% (5 y) 61mo

Wilhelm et al. (submitted)

OS

HDT / autoSCT for consolidation after CHOP-

therapy in peripheral T-cell lymphoma

Overall Survival

(n=111)

++

++++

++++++ +++++++

++++ +

+++++++++++ ++++++++++++ ++++++ + ++

0 20 40 60 80 100 120

Time (months)

0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1,0

CHOEP-14 x 3

CR, PR NC,PD

CHOEP-14 x 3

stem cell collection

NLG-T-01: Design

CR, PR NC,PD

BEAM

Follow-up

Excluded:

1) alk-1 pos

ALCL T/0

2) CTCL

3) Leukemic T-

NHL

Nordic

Lymphoma

Group

d'Amore F et al. JCO 2012;30:3093-3099

Kaplan-Meier estimates of (A) overall (OS) and (B) progression-free survival (PFS) for the entire NLG-T-01 cohort and (C) OS and (D) PFS for the four largest histologic subtypes.

d'Amore F et al. JCO 2012;30:3093-3099

Allogeneic transplantation

as part of first-line therapy

AlloSCT in newly diagnosed patients with p-TCL

Corradini et al. Leukemia 2014; 28: 1885-91



PD (n=5)

PD (n=6)

PD (n=7)

Only 61% of patients were transplanted!

Allogeneic or Autologous Transplantation

as First-Line Therapy for Younger Patients with

Peripheral T-Cell Lymphoma

Results of the Interim Analysis of the AATT Trial

Norbert Schmitz, Maike Nickelsen, Bettina Altmann, Marita Ziepert, Kamal

Bouabdallah, Christian Gisselbrecht, Sébastien Maury, Guillaume Cartron,

Emmanuel Gyan, Arnaud Jaccard, Laurence Sanhes, Philippe Gaulard,

Andreas Rosenwald, Lorenz Truemper, Bertram Glass, Peter Reimer,

Wolfgang Herr, Martin Wilhelm and Olivier Tournilhac

GERMAN HIGH-GRADE

LYMPHOMA STUDY GROUP

(DSHNHL)

THE LYMPHOMA

STUDY ASSOCIATION

(LYSA Lymphomes T)

C H O E P

C H O E P

C H O E P

C H O E P

D H A P

B E A M

A S C T

PBSC harvest

C H O E P

C H O E P

C H O E P

C H O E P

D H A P

F B C

S C T

CR, PR, NC

No donor available

R

Days 1 15 29 43 64 4–6 weeks

CR, PR, NC

THE LYMPHOMA

STUDY ASSOCIATION

(LYSA Lymphomes T)

Inclusion criteria

• Patients 18-60 years

• ECOG 0-3

with

• Peripheral T-cell lymphoma, NOS

• Angioimmunoblastic T-cell lymphoma

• Anaplastic large cell lyphoma, 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 and aalPI 0

GERMAN HIGH-GRADE


(DSHNHL)

BEAM: BCNU 300 mg/m2, Ara-C 800 mg/m2, VP-16 800 mg/m2, Mel 140 mg/m2

FBC: Fludara 125 mg/m2, Busulfan 12 mg/kg, Cyclo 120 mg/kg

autoSCT (n=30)

alloSCT (n=28)

total (n=58)

Male 17 (57%) 20 (71%) 37 (64%)

Age, median (range) 49 (28, 60) 50 (24, 60) 50 (24, 60)

LDH > UNV 20 (67%) 19 (68%) 39 (67%)

ECOG > 1 7 (23%) 5 (18%) 12 (21%)

Stage III/ IV 26 (87%) 26 (93%) 52 (90%)

Extranod. involvement > 1 11 (37%) 7 (25%) 18 (31%)

aaIPI 0

1

2

3

1 (3%)

10 (33%)

14 (47%)

5 (17%)

1 (4%)

8 (29%)

15 (54%)

4 (14%)

2 (3%)

18 (31%)

29 (50%)

9 (16%)

Peripheral T-cell lymphoma, NOS 11 (36%) 14 (50%) 25 (43%)

Angioimmunoblastic T-cell lymphoma 7 (23%) 9 (32%) 16 (28%)

Anaplastic large cell lymphoma, ALK-neg

6 (20%) 1 ( 4%) 7 (12%)

Other1 6 (20%) 2 ( 8%) 8 (28%)

AATT study: patient characteristics

1 NK/T-cell lymphoma (1), Intestinal T-/NK-cell lymphoma (3), Hepatosplenic gamma-delta lymphoma (3), Subcutaneous panniculitis-like PTCL (1)

THE LYMPHOMA

STUDY ASSOCIATION

(LYSA Lymphomes T)

GERMAN HIGH-GRADE


(DSHNHL)

R

30 pts

28 pts

C H O E P

C H O E P

30 → 28 pts

28 → 27 pts

change of histology (2)

PD (1)

C H O E P

C H O E P

28 → 25 pts

27 → 26 pts

PD(1)

toxicity (1)

other (1)

PD (1)

C H O E P

C H O E P

25 → 23 pts

26 → 25 pts

PD(2)

PD (1)

C H O E P

C H O E P

23 → 21 pts

PD(2)

PD (3)

CR, PR, NC

D H A P

D H A P

CR, PR, NC

21 → 19 pts

22 → 13 pts

PD(2)

PD (4)

no donor (5)

25 → 22 pts

PBSC harvest

B E A M

A S C T

mobil. fail (1)

no donor (n=5)

F B C

S C T

23 pts

13 pts

AATT study: course of therapy

autoSCT

(n=30)

alloSCT

(n=28)

Total

(n=58)

Complete as per protocol

19 (63%) 17 (61%) 36 (62%)

Off study 11 (37%) 11 (39%) 22 (38%)

AATT study: cause of death according to treatment arm (ITT)

autoSCT

(n=30)

alloSCT

(n=28)

Total

(n=58)

Lymphoma 10 6 16

Salvage treatment 1 1 2

Hemorrhage after salvage

0 1 1

Study treatment 0 6 (4 early, 2 late)

6

PTLD 0 1 1

AATT study: cause of death after SCT

autoSCT

(n=30)

alloSCT

(n=28)

Total

(n=58)

Lymphoma 6 0 6

Salvage treatment 1 0 1

NRM 0 7* 7*

* includes one patient with PTLD

AATT study: updated results of the interim analysis

OS according to treatment arm

time (months)

0 10 20 30 40 50

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

autoSCT (n=30)

p=0.362

median observation time: 26 months

alloSCT (n=28)

Salvage therapy including

autologous transplantation

in relapsed / refractory

T-cell lymphoma

No randomized study done!

(A) Second progression-free survival (median, 3.7 months) of patients treated with

chemotherapy (n = 89) with relapsed or progressive peripheral T-cell lymphoma (PTCL) and

(B) overall survival (median, 6.5 months) after first relapse or progression of PTCL.

Mak V et al. JCO 2013;31:1970-1976

©2013 by American Society of Clinical Oncology

Treatment Strategies in Peripheral T-cell

Lymphoma Relapsed/Refractory Disease


BEAM

A

S

C

T

Chemotherapy

DHAP

Allogeneic Tx DHAP

FBC

S

C

T

HDT/ autoSCT in pTCL

36%

50%

0,00

0,20

0,40

0,60

0,80

1,00

0 12 24 36 48 60 72 84 96 108

Months after SCT

OS

0,00

0,20

0,40

0,60

0,80

1,00

0 12 24 36 48 60 72 84 96 108

Months after SCT

PFS

Retrospective analysis of T – cell lymphoma patients

at all stages treated with different preparatory regimens

Allogeneic transplantation

In relapsed/refractory T-NHL

AlloSCT in pTCL: The CIBMTR Experience

Smith S M et al. JCO 2013;31:3100-3109

Wulf et al., BMT(in press)

n=95

patients at risk

(OS)

OS

PFS

95 58 40 30 22 14 9 5 4 3

OS: 46% + 6%

PFS: 43% + 5%

AlloSCT in pTCL: The German Experience

(n=95)

Results in Allogeneic Transplantation for

Relapsed / Refractory T-Cell Lymphoma

French Study EFS 53% at 5 yrs

EBMT Study (AILT only) PFS 53% at 3 yrs

CIBMTR Study PFS 37% at 3 yrs

German Study PFS 43% at 3 yrs

40-50% of patients with relapsed / refractory disease survive long-term

Treatment of PTCL: new drugs



•Alemtuzumab

•Romidepsin

•Pralatrexate

•HDAC inhibitors

•Antiangiogenic drugs

•mTOR inhibitors

•Aurora A kinase inhibitors

Anaplastic large cell lymphome (ALCL), ALK-negative or positive

•Brentuximab Vedotin

•Crisotinib

Fig 2: TCR signalling in nodal TFH derived lymphomas. Several genes associated with the TCR

signalling are mutated in AITL and TFH-like PTCL-NOS. Pathways were reconstructed using the Ingenuity

pathway analysis (IPA) tools and the KEGG database, and were subsequently used to group define mutant

variants in survival and gene set enrichment analysis.

Fig 4: Enriched gene signatures in patients with or without mutations in TCR-related signalling genes.

Gene sets enriched in patients with mutated or non-mutated TCR-related signalling (irrespective of RHOA status)

genes indicate that pathway mutants have more proliferative activity, and express genes associated with TCR

activation. Genes tested in the enrichment analysis were selected from signatures relevant in T and B cell

differentiation and activation.

JAK-STAT

target genes

PIK3

target genes

NF-kB related

Ca2+ signalling

target genes

IRF4

target genes

Proliferation

Glycolysis

Proximal TCR

components

How I treat the peripheral T-cell

lymphomas

The American View

Moskowitz AJ et al.

Blood 2014; 123: 2636-2644

BACKUP

Treatment Strategies in

Peripheral T-cell Lymphoma First-Line Therapy

CHO(E)P


HDT

A

S

C

T

CHO(E)P

Treatment Strategies in Peripheral T-cell

Lymphoma Relapsed/Refractory Disease


BEAM

A

S

C

T

Chemotherapy

DHAP

Allogeneic Tx DHAP

FBC

S

C

T

Response autoSCT

(n=30)

alloSCT

(n=28)

Total

(n=58)

CR/CRu 10 (33%) 11 (39%) 21 (36%)

CR/CRu and PD within 2

months 1 ( 3%) 1 ( 4%) 2 ( 3%)

PR 5 (17%) 2 ( 7%) 7 (12%)

NC 2 ( 7%) 0 ( 0%) 2 ( 3%)

PD 10 (33%) 10 (36%) 20 (35%)

Unknown 2 ( 7%) 0 ( 0%) 2 ( 3%)

Treatment - related death 0 ( 0%) 4 (14%) 4 ( 7%)

AATT study: response according to treatment arm

Conclusions

• Interim analysis of 58 patients led to termination of the study because

conditional power analysis showed low probability to confirm hypothesis

• 38 % of pts could not proceed to auto- or alloSCT as per protocol

• AutoSCT gave results comparable to other studies

• GvL-effect of alloSCT counterbalanced by high TRM

• No significant difference between treatment arms (low patient numbers!)

• Final analysis on 104 patients expected 2017

Treatment of PTCL: Summary

Improve induction Consolidate/maintain response

100% 65% 50% 48%

Improve induction

• C+ Alemtuzumab

• C+ Brentuximab Vedotin

• C+ Romidepsin

• C+ Pralatrexate

Consolidate response

• Auto SCT

• Allo SCT

• MoAb

• Pralatrexate

• HDAC inhibitors

Maintain response

• MoAb

• Antiangiogenic drug

• mTOR inhibitor

• Aurora A kinase inhibitors

1st line treatment of PTCL

Improve

induction Consolidate/maintain response

100% 65% 50% 48%

46

Study Design and Key Eligibility Criteria

• 329 patients were randomized at 78 sites in North America and Europe

47

Progression-Free Survival in ITT population

PFS per IRF PFS per Investigator†

HR=0.57, P=0.001 HR=0.50

* Regularly scheduled CT scans † Includes information from both radiographic assessments and clinical lymphoma assessments

Survival of relapsed patients after first-line therapy with

MegaCHOEP or CHOEP-14 (n=25)

DSHNHL

Allo SCT

0 10 20 30 40 50 60 70 80 90 100

Time after progression (months)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

OS

(p

rop

ort

ion

)


MegaCHOEP or CHOEP-14 (n=25)

DSHNHL

Log-Rank-test p = .01209

0 10 20 30 40 50 60 70 80 90 100

time after progression (months)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Overa

ll s

urv

ival

(pro

po

rtio

n)

no allogeneic Tx. n=17

allogeneic Tx. n=8


MegaCHOEP or CHOEP-14

DSHNHL

0 10 20 30 40 50 60 70 80 90 100

Time after progression (months)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

OS

(p

rop

ort

ion

) n=25

Recommended approach to patients with relapsed peripheral T-cell lymphomas (PTCLs) regarding additional therapies and goals of care.

Lunning M A et al. JCO 2013;31:1922-1927


Allo SCT in aggressive lymphoma : DSHNHL Study

Tacrolimus

MMF

Salvage

Therapy Allo SCT

F

25

F

25

F

25

F

25

F

25

B

4

B

4

B

4

C

60

C

60

R R R R R R

MMF

Tacrolimus

R CR

PR

SD

no

ATG optional ATG

F=fludarabine, B=busulfan, C=cyclophosphamide, R=rituximab, ATG=anti-thymoglobulin

18 - 65 years

Relapse < 12m

Refractory disease

Post auto SCT

off study

3 4 5 6 25 26 27 28 week -8 -5 week -9 -8 -7 -6 -5 -4 -3

R R

RIC-allo in pTCL. The French Experience

Le Gouill et al., JCO 2008

(A) Second progression-free survival (PFS) of patients treated with chemotherapy (n = 89) with relapsed or progressive peripheral T-cell lymphoma (PTCL) by performance status (PS;

median second PFS: PS 0 or 1, 5.0 months; PS ≥ 2, 1.8 months) and (B) overall...

Mak V et al. JCO 2013;31:1970-1976


mCHOEP 1

CYC 1500

ADR 70

VCR 2

ETO 600

PRD 500

mCHOEP 2

CYC 4500

ADR 70

VCR 2

ETO 600 (960)

PRD 500

mCHOEP 3

CYC 4500

ADR 70

VCR 2

ETO 600 (960)

PRD 500

mCHOEP 4

CYC 6000

ADR 70

VCR 2

ETO 1480

PRD 500

PBPC

PBPC

PBPC

Mega-CHOEP Protocol

OS in PTCL-NOS

International T-cell Lymphoma Project. J Clin Oncol 2008. 26; 25: 4124-4130

OS in the common subtypes

of T-cell lymphoma

International T-cell Lymphoma Project. J Clin Oncol 2008. 26; 25: 4124-4130

The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation

Allo SCT in pTCL :

histologic subtypes n = 91

Peripheral T-cell lymphoma 54 (59.3%)

Anaplastic large cell lymphoma 26 (28.6%)

ALK pos 5 (5.4%)

ALK neg 6 (6.5%)

ALK unknown 15 (16.4%)

T-NHL unspecified 11 (12%)

(preliminary)

The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation The European Group for Blood and Marrow Transplantation

Allo SCT in pTCL:

patient characteristics (n = 91)

of eligible pts % of missing data

Male (%) 57.1

Age at diagn. (years) 39.9 (15-64)

SDaye III/IV (%) 90.4 19.8

Elevated LDH at diagnosis 54.3 49.5

aaIPI high / high int. (%) 63.8 48.4

Median time to SCT (months) 18 (3 – 233)

> 2 prev. treatment lines (%) 66.1 35.2

Previous auto SCT (%) 35.2

Stem cell source PB / BM (%) 73.6 / 23.1

variable univariate p multvariate p RR 95% CI

lower limit

upper limit

age </> 50 0.39492 n.s.

m/f 0.86717 n.s.

diag. to tx </> 1y 0.5494 n.s.

lines ctx </>2 0.02816 0.013 2.368 1.201 4.667

prior auto y/n 0.61816 n.s.

PD / CR, PR, SD 0.00128 0.243 1.686 0.702 4.049

IPI 0,1,2 / 3,4 0.0079 0.241 1.821 0.669 4.956

LDH nl./elev. 0.00260 0.615 1.187 0.619 2.316

ECOG 0,1 / >2 0.01126 0.706 1.209 0.451 3.242

stage 1/2 vs 3/4 0.32942 n.s.

EN 0/1 vs >1 0.53926 n.s.

MRD / MUD,MMD 0.50185 n.s.

ATG / no ATG 0.17102 n.s.

aGvHD 0 / 1-4 0.01396 0.678 0.361 1.306

cGvHD lim. vs ext. 0.05266 n.s.

61

61

DSHNHL

Wulf et al., submitted

n=95 B A n=95

OS

n=97 n=97

PFS

n=97

OS OS n.s.

OS n.s.


OS - IPI score for all patients (n=320)

IPI 0

(n=93)

IPI 1

(n=70)

IPI 2

(n=80)

IPI 3

(n=48)

IPI 4

(n=25)

IPI 5

(n=4)

0 10 20 30 40 50 60 70 80 90 100 110

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Pro

po

rtio

n

Months


Autologous Tx

in T-cell lymphoma

C

H

O

P

C

H

O

P

C

H

O

P

C

H

O

P

C

H

O

P

C10 C10 C10 C10 C10 C10

C 3

PD

CR,PR

A)

B)

C

H

O

P

C

H

O

P

C 3

C10

C20

C30

HyperCHidam

HyperCHidam

CR,PR

PD

autoSCT

alloSCT

C

H

O

P

Corradini et al. (submitted)

Up-front chemo-immunotherapy with or without stem cell

transplantation in patients with peripheral T-cell lymphomas

results of a prospective multicenter phase II study

66

66

DSHNHL

Wulf et al., submitted

Reimer et al., JCO 2009; 27:106

PFS

HDT / autoSCT as part of 1st-line therapy in

peripheral T-cell lymphoma

DSHNHL 2006-1A: study design

First-line treatment of mature (peripheral)

T-cell lymphoma (PTCL) for patients ≤ 60 years

Inclusion criteria • Peripheral T-cell lymphoma,

unspecified

• Angioimmunoblastic T-cell lymphoma

• Anaplastic large cell lyphoma, 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 aalP10

C H O E P

C H O E P

C H O E P

C H O E P

D H A P

B E A M

A S C T

PBSC harvest

CR, PR, NC

C H O E P

C H O E P

C H O E P

C H O E P

D H A P

F B C

S C T

CR, PR, NC

No donor available

R

Days 1 15 29 43 64 4–6 weeks

March 2014: 90/ 146 patients randomized

Treatment Strategies for patients with relapsed T-Cell lymphoma

chemotherapy :

platinum-based regimens, gemcitabine, methotrexate……..

new drugs:

alemtuzumab, pralatrexate, romidepsin, brentuximab, vedotin…….

high-dose therapy / autologous transplantation


0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Pro

po

rtio

n

0 10 20 30 40 50 60 70 80 90 100 110

Months

1: ALK+ (n= 73)

2: ALK- (n= 108)

3: PTCL (n= 68)

4: AILT (n= 28)

5: T/NK (n= 18)

p-values:

2 3 4 5

1 <0.001 <0.001 0.001 <0.001

2 0.350 0.958 0.339

3 0.537 0.700

4 0.472


ALK+ 88.8% (95% CI: 80.8%-96.8%)

ALK- 63.3% (95% CI: 53.9%-72.7%)

3-years OS-rate:

PTCL 52.9% (95% CI: 40.2%-65.6%)

AILT 65.9% (95% CI: 47.7%-84.1%)

T/NK 48.9% (95% CI: 25.4%-72.4%)

OS - histological subtypes (n=295)

DSHNHL

Gemcitabine in PTCL

Study Regimen N ORR

Sallah et al

Br J Haematol. 2001 Gemcitabine monotherapy 10 60%

Zinzani et al

Phase II

Ann Oncol. 2010

Gemcitabine monotherapy 39 69%

Royal Marsden

Phase II

Arkenau. Haematologica

2007

GEM-P 16 69%

Spencer et al

Pilot study

Intern Med J. 2007

VGF 10 70%

Kim et al

Pilot study

Cancer Chemother

Pharmacol. 2006

CHOP-EG 26 77%

CHOP-EG=CHOP-etoposide, gemcitabine; GEM-P=gemcitabine, cisplatin, methylprednisolone;

VGF=vinorelbine, gemcitabine, filgrastim.

Courtesy Dr. Advani



-6 -4 -3 -2 -1 0 +1 +3 +6 +30 +60 +70 +90 +120 +150 +180

Thiotepa 10 mg/kg

Fludarabine 30 mg/mq

Cyclophosphamide 30 mg/kg

Allo-HSCT

Cyclosporine (+ ATG 7.5 mg/kg for alternative donors)

MTX

MTX MTX

RIC treatment plan

Corradini et al. JCO 2004

Graft-Versus-Lymphoma Effect in Relapsed Peripheral

T-Cell Non-Hodgkin’s Lymphomas After Reduced-

Intensity Conditioning Followed by Allogeneic

Transplantation of Hematopoietic Cells

Corradini et al. JCO 2004

T-cell lymphomas in the Swedish Lymphoma Registry

OS - extranodal subtypes

SPTCL

HSTCL

EATL

NK/T

Ellin et al., Blood 2014; 124:1570-77

How I treat the peripheral T-cell lymphomas - portal.ebmt.org · d'Amore F et al. JCO 2012;30:3093-3099 . Allogeneic transplantation as part of first-line therapy . AlloSCT in newly

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