Managing T-Cell Lymphoma

PTCL
OK, Now What?

Steven M. Horwitz M.D.
Assistant Attending
Lymphoma Service
Memorial Sloan-Kettering Cancer Center

Prognosis:
Overall and Failure-free Survival
1.0

0.9
Peripheral T-cell Lymphoma-NOS
0.8
Proportion

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Time

Armitage J, et al. J Clin Oncol. 2008;26:4124–4130, International T-cell Classification Project

Current Problems with PTCL

 Current Problems
 Confusing terminology/ Difficult Diagnosis
 Poor Prognosis
 Results with “Standard” Therapy

 Thinking about solutions
 High-Dose therapy
 New (or not so new) Drugs
 Ways to move forward

WHO 2008 CLASSIFICATION OF MATURE T/NK-CELL
NEOPLASMS

T-cell prolymphocytic leukemia Mycosis fungoides
T-cell large granular lymphocytic leukemia Sezary syndrome
Chronic lymphoproliferative NK cells Primary cutaneous CD30+
lymphoproliferative
Aggressive NK-cell leukemia
Primary cutaneous anaplastic large cell
Adult T-cell lymphoma/leukemia
Lymphomatoid papulosis
Systemic EBV-positive T-cell lymphoma
Borderline lesions
Extranodal NK/T-cell lymphoma, nasal type
Subcutaneous panniculitis-like T-cell
Enteropathy-type intestinal T-cell lymphoma
Primary cutaneous gamma-delta T-cell
Hepatosplenic T-cell lymphoma
Hydroa vacciniforme lymphoma
Angioimmunoblastic T-cell lymphoma (AITL)
Primary cutaneous aggressive
Anaplastic large cell lymphoma, ALK-positive
epidermotropic CD8+ cytotoxic T-cell
Anaplastic large cell lymphoma, ALK-negative
Primary cutaneous small/medium CD4+ T-
Peripheral T-cell lymphoma, NOS cell lymphoma (provisional)

Peripheral T-cell Lymphomas, PTCL refers to mature T-cell lymphomas (Pathology
Definition)
PTCL

“Systemic T-cell Lymphoma”
Peripheral T-cell lymphoma NOS “CTCL”
Angioimmunoblastic T-cell lymphoma Mycosis Fungoides
Anaplastic Large Cell-ALK-1 negative Sezary syndrome
Subcutaneous panniculitis-like
Anaplastic Large Cell-ALK-1 positive
Primary cutaneous ALCL
Enteropathy-type intestinal lymphoma
Lymphomatoid papulosis
Extranodal NK/T-cell lymphoma-nasal Primary cutaneous small/medium CD4+ T-
Adult T-cell leukemia/lymphoma cell lymphoma
Hepatosplenic T-cell lymphoma (may be derived from an Primary cutaneous aggressive
immature T-cell) epidermotropic CD8+ cytotoxic T-cell
lymphoma

Cancers of Immature T-cells
lymphoblastic lymphoma and acute
lymphoblastic leukemia

Expert Agreement: Consensus Diagnosis

ALCL, ALK+ 97% PTCL, unspecified 75%

ATLL 93% Panniculitis-like 75%

Nasal NK/T-cell 92% ALCL, ALK- 74%

Angioimmunoblastic 81% Hepatosplenic 72%

Enteropathy-type 79% Cutaneous ALCL 66%

Vose JM, et al. J Clin Oncol. 2008;26:4124-4130.

Expert Agreement Upon Re-review

Overall agreement 81%

Reviewer 1 67%

Reviewer 2 74%

Reviewer 3 83%

Reviewer 4 87%

Reviewer 5 95%

Data from Dennis Weisenberger, Int PTCL Project

International PTCL Study
Major NHL Types by Region

Percent NA EU FE

PTCL, unspecified 34.4 34.3 22.4

Angioimmunoblastic 16.0 28.7 17.9

Anaplastic, ALK+ 16.0 6.4 3.2

Anaplastic, ALK- 7.8 9.4 2.6

NK/T-cell 5.1 4.3 22.4
ATLL 2.0 1.0 25.0


Mature T and NK Lymphomas:
FFS of Different Histologies
1.0

0.9

0.8

ALCL ALK+
Proportion

0.7

0.6

0.5

0.4

0.3 ALCL ALK-
0.2 AITL
PTCL
0.1 NK/T-nasal type
0.0 ATLL EATCL
0 1 2 3 4 5 6 7 8 9 10 11 12
Time

.


Baseline with CHOP/CHOP-Like: PTCL-U BCCA
OS by IPI

N=117

Savage et al. Annals of Oncology 2004; 15:1467–1475.

Autologous stem cell transplantation as first-line
therapy in PTCL: Results of a prospective
multicenter study
PTCL 39%
 N=83 AITL 33%
 CHOP x 4-6 ALCL 16%
 IF CR/PR Med age 46.5 (30-65)
 mobilized with DexaBEAM or
ESHAP AA-IPI L-LI 49%
 TBI + CY-ASCT HI-H 51%
 Median F/U: 33 months
CR/CHOP 39%
PR/CHOP 40%
ASCT 66%
POD 29% (22% CHOP)
Reimer, P. et al et al. JCO vol 27, Jan 2009

therapy in PTCL: Survival

3-year survival 48%
Overall OS: 3-year DFS: 53%
Disease-free survival

1 1

0,8 0,8

0,6 0,6

0,4 0,4

0,2 0,2

0 0
0 12 24 36 48 60 0 12 24 36 48 60

Time (months)
time (months) time (months)
Time
(months)
(n=83)
(n=83) (n=83)
(n=55)

Reimer, P. et al et al. JCO vol 27, Jan 2009

therapy in PTCL: Survival

Overall survival
Overall Survival OverallSurvival
Overall
survival
(Transplanted vs. non-transplanted) (IPI: high/intermediate high vs. low/intermediate low)
Transplanted vs. non-transplanted IPI: high / interm.high vs. low /
1
1
interm.low
p< 0.001 p= 0,1799
0,8 0,8

0,6 0,6

0,4 estimated 3-year OS: 71% vs. 11% 0,4

0,2 0,2

0
0
0 12 24 36 48 60 0 12 24 36 48 60
Time (months)
time (months) time (months)
Time (months)

non-transplanted (n=28)
transplanted (n= 55) transplanted (n=55)
non-transplanted (n= 28) high / interm.high (n= 42)
IPI: high/intermediate high (n=42) IPI:low /intermediate low(n= 41)
low / interm.low (n=41)

CR vs PR p=0.22
PFS 36%-no plateau
Reimer, P. et al. J Clin Oncol; 27:106-113 2009

CIBMTR Auto and Allo for PTCL:
Outcomes excluding patients in CR1
100
PFS 100
OS 100
NRM
P <0.0001
90 90 90

80 80 80

70 70 70
Auto (N = 75)
60 60 60
Auto (N = 75)
50 50 50

40 40 40
Allo (N = 108) Allo (N = 108)
30 30 30
Allo (N = 108)
20 20 20

10 10 10 Auto (N = 75)
P=NS P=NS
0 0 0
0 12 24 36 48 0 12 24 36 48 0 12 24 36 48
Months Months Months

Smith et al, ASH 2010 abstract 689

ICE and Planned ASCT for Relapsed/Refractory
T-cell Lymphoma: PFS from ICE
Progress Free Survival PFS: Relapsed versus Refractory

1.0 1.0

0.8 0.8

0.6
0.6

% %

ALL, N=40 0.4

Rel, N=22
0.4

0.2
0.2

Ref, N=18
0.0
0.0
0 12 24 36 48 60 72 84 96 108 120 132
0 12 24 36 48 60 72 84 96 108 120 132

PFS ICE months PFS ICE months

Response to ICE 70% (28/40)
Received ASCT 68% (27/40) Horwitz et al, ASH 2005

Retrospective Analysis of 77 PTCL Patients Who Underwent
Allogeneic Stem-cell Transplantation

AITL (n=11) 80%

PTCL (n=27) 63%
5 year OS 57%

ALCL (n=27) 55%
5 year EFS 53%

Other (n=12) 33%

-Response to DLI 2/2

Le Gouill, S. et al. J Clin Oncol; 26:2264-2271 2008

Retrospective Analysis of PTCL Patients Who Underwent
Allogeneic Stem-cell Transplantation
Societe´ Francaise De Greffe De Moelle Et De Therapie Cellulaire

REL/REFR
Histologies N=77
-ALCL-27
-PTCL-NOS-27
-AITL-11
-NK/T-cell-5
5 year TRM 34%
-HSTCL-3
-T-LGL-1
-EATCL-1
-HTLV– 2

myeloablative
Le Gouill, S. et al. J Clin Oncol; 26:2264-2271 2008
conditioning
regimen-57

Current Problems with PTCL

 Current Problems
 Confusing terminology/ Difficult Diagnosis
 Poor Prognosis
 Results with “Standard” Therapy

 Thinking about solutions
 High-Dose therapy
 New (and not so new) Drugs
 Ways to move forward

Is there an “R-CHOP” for TCL?
Alemtuzumab- anti-CD52 antibody
 N=14, Rel/Refr-Phase II, standard dosing (30 mg iv 3x/week)1
 10 PTCL, nos, RR 36% (3CR/2PR)
 5 deaths-closed early (TB, zoster, aspergillus)
 N=10, Phase II -10 mg x 12 doses (4 weeks) 2
 PTCL nos 6, CTCL 4
 Response 50% in PTCL, CR2/PR1
 Less toxic

Denileukin diftitox-fusion protein-IL2-diphtheria toxin
 N=27, (PTCL 19) Phase II, standard dosing3
 48%RR , not myelosuppressive
1. Enblad et al. Blood. 2004;103:2920-2924.
2. Zinzani et al Haematologica. 2005;90:702-703.
3. Dang et al British Journ Haematol 136:439-447, 2007

Alemtuzumab and CHOP chemotherapy as first-line
treatment of PTCL: results of a GITIL prospective
multicenter trial

A-30 mg + CHOP Q 4 weeks x 8
N=24 (PTCL/AITL 20) 2 year FFS 48%

IPI 0-1 33%
2-3 58%
4-5 8%

CR ALL 70.8%
PTCL 50% 2 year OS 53%
AITL 100%

Gallamini et al, Blood 110:2316-
2323; 2007

Issues with Alemtuzumab + CHOP
 Toxicity
– Gallamini et al
– Grade 4 Infection-17%
– Sepsis, Aspergillosis, JC virus, PCP

– Kim et al
– Toxicity-Grade 3-4
• Neutropenia 90%, Lymphopenia 95%, Febrile neutropenia 55%
• Infectious deaths 10%
• Study halted early due to SAE

 Heterogeneity of CD52 expression
– Series of PTCL 35-40%*
– Down-regulated in PTCL?
– Varies by technique Flow vs Immunohistochemistry

*Piccaluga et al Haematologica 2007 92:566-567, Rodig et al. Clin Cancer Res 2006;12:7174

Denileukin Diftitox (DD) + CHOP in First-Line
PTCL (CONCEPT Trial)

 Multicenter phase II study of patients with aggressive T-cell NHL
 Treatment: DD 18 μg/kg/d on Days 1-2, CHOP on Day 3, G-CSF or
filgrastim on Day 4
 N=49 (80% PTCL/AITL/ALCL)
 7 patients completed only 1 cycle of therapy
– 3 deaths after cycle 1 (2 cardiac, 1 rhabdomyolysis)
– 4 discontinued due to toxicity
 Efficacy
– ORR overall: 68%; 57% CR
– ORR (≥2 cycles): 86%; 73% CR
– Median PFS 12 mos; estimated 2-year OS 60%

Foss FM, et al. ASCO 2010. Abstract 8045.

Treatment and Prognosis of Mature T-cell and
NK-cell Lymphoma: an analysis of patients with T-cell
lymphoma treated in studies of the German High-Grade
Non-Hodgkin’s Lymphoma Study Group (DSHNHL)

•7 trials: German High-Grade Non-Hodgkin’s Lymphoma Study Group
•343 patients
•Most received 6-8 courses of CHOP or CHOEP (Hi-CHOEP, or
MegaCHOEP)
•56% ALCL, 8% AITL

Histology N 3 yr EFS 3 yr OS
ALCL ALK+ 78 75.8% 89.8%
ALCL, ALK- 113 45.7% 62.1%
PTCLU 70 41.1% 53.9%
AITL 28 50.0% 67.5%

Schmitz et al., Blood First Edition Paper, prepublished online July 21, 2010

NK-cell Lymphoma: Event-free survival
Younger patients treated on the NHL-B1 trial

EFS


NK-cell Lymphoma: Event-free survival
Younger patients treated on NHL-B1/Hi-CHOEP trial

EFS EFS
ALCL, ALK+ Other subtypes


Pralatrexate
cMOAT/
MRP
RFC-1 Plasma membrane ATPase
ATP
PDX PDX PDX
FPGS PDX(G)n
(& Natural ATP + MgCl2
Folates)
Lysosome ADP
Gn
PDX(G)n
PDX
FPGH
+ SH
cysteine cysteine ? cysteine
TMTX

cysteine

Compared to MTX
PDX more efficiently enters tumor cells
(RFC-1) and is more readily polyglutamylated (FPGS)

PROPEL Pivotal Trial: Pralatrexate in
Relapsed/Refractory PTCL

Primary endpoint
N=115 • Response rate
• Single-arm Pralatexate 30 mg/m² IV Secondary endpoints
• Phase II x 6 weeks in 7 week • Duration of response
• Relapsed or cycles* • Overall survival
refractory PTCL • Progression-free
survival

*No pre-medications were required and patients also received vitamin B12 every 8-10 weeks,
and 1 mg of oral folic acid daily.

O’Conner OA, et al. J Clin Oncol. 2011;29:1182-1189.

Pralatrexate in Relapsed/Refractory PTCL

 Median number prior systemic therapies: 3 (range, 1-12)
Outcome Patients (N=109 evaluable)
ORR 29%
• CR 11%
• PR 18%
Median duration of response 10.1 months
Median PFS 3.5 months
Median OS 14.5 months


PROPEL: Response Analysis by Subsets
Number of Proportion of
Factor Patients Patients ORR
Age
• < 65 years 70 64% 27%
• ≥ 65 years 39 36% 33%
Number prior systemic
regimens
• 1 23 21% 35%
• 2 29 27% 24%
•≥3 57 52% 30%
Prior transplant
• Yes 18 17% 33%
• No 91 83% 29%
Histology
• PTCL-NOS 59 54% 32%
• AILT 13 12% 8%
• ALCL 17 16% 35%
• Transformed MF 12 11% 25%
• Other 8 7% 38%


PROPEL
Adverse Events ≥ Gr 3 Occurring in ≥ 3% of Patients (n=111)

Any Grade Grade 3 Grade 4
Mucosal inflammation* 70% 17% 4%
Thrombocytopenia** 41% 14% 19%1
Nausea 40% 4% 0%
Fatigue 36% 5% 2%
Anemia** 34% 16% 2%
Neutropenia** 24% 13% 7%
Dyspnea 19% 7% 0%
Hypokalemia** 15% 4% 1%
Abnormal LFTs* 13% 5% 0%
Abdominal pain 11% 4% 0%
Leukopenia** 11% 3% 4%
Febrile Neutropenia 5% 5% 0%
Sepsis 5% 3% 2%
Hypotension 5% 3% 1%
*includes 6 MedDRA preferred terms **includes 2 MedDRA preferred terms ***includes 3 MedDRA preferred terms
1- Only 5 patients had platelet count < 10,000 μL
O’Connor OA, et al JCO Jan 18 2011

Pralatrexate for CTCL: Efficacy Results
Cohort Pralatrexate Dose mg/m2 Response Response
Schedule Rate Type
1 30- 3/4 weeks 100% (2/2) 2 PR
2 20- 3/4 weeks 67% (2/3) 2 PR
3 20- 2/3 weeks 57% (4/7) 1 CR/3 PR
4 15- 3/4 weeks 50% (3/6) 3 PR
5 15- 2/3 weeks 0 (0/3) ---
6 10- 3/4 weeks 10% (1/10) 1 CR
Overall 39% (12/31) 2 CR/10 PR
Doses >15 mg/m2, 3/4 weeks 61% (11/18)

“Optimal” dose 15 mg/m2, 3/4 weeks 10/22 (45%)

Horwitz SM, Kim Y, Foss F, et al, ASH Annual Meeting., 2010;

Response by CTCL Subtype and Stage (N = 54)
CTCL Subtype (per Stage Rate at Optimal Response Rate Overall
Investigator) Dose/Sched at ≥ 15 mg/m2 Response
% (n/N) 3/4 weeks Rate
% (n/N) % (n/N)

MF IB 60% (3/5) 63% (5/8) 50% (5/10)
IIB 67% (4/6) 67% (8/12) 53% (9/17)
III 50% (1/2) 50% (1/2) 50% (1/2)
IVA 60% (3/5) 60% (3/5) 50% (3/6)
IVB 0% (0/1) 0% (0/1) 0% (0/1)

Sézary IIB 0% (0/1) 0% (0/1) 0% (0/1)
III 33% (1/3) 25% (1/4) 25% (1/4)
IVA 33% (1/3) 33% (1/3) 13% (1/8)
IVB 0% (0/1) 50% (1/2) 50% (1/2)
PC-ALCL IIB ------- 100% (1/1) 100% (1/1)

All patients 45% (13/29) 51% (21/41) 41% (22/54)

Horwitz SM, Kim Y, Foss F, et al, ASH Annual Meeting., 2010;

Romidepsin in PTCL

 A pan-histone deacetylase (HDAC) inhibitor
 FDA-approved in 2009 for use in patients with CTCL
who have received ≥ 1 prior systemic therapy
 Pivotal trial in PTCL presented at ASH 2010

Pivotal Trial of Romidepsin in Relapsed/Refractory
PTCL

Primary endpoint
N=131 • CR rate by independent
• Single-arm review
Romidepsin 14 mg/m2 IV
• Phase II Secondary endpoints
on Days 1,8,15 every 28
• PCTL failing ≥1 • CR rate by investigator
days
prior systemic assessment
therapy • ORR
• Systemic disease • Duration of response
• Time to first response
T-cell lymphoma subtypes (n): • Time to progression
• PTCL-NOS (53) • Safety, tolerability
• AITL (21)
• ALCL (ALK-1-neg) (16)  Median age: 61 years (range, 20-83)
• Other (10)  Median of 2 prior regimens (range, 1-6)
 62% refractory to frontline therapy
Coiffier B, et al. ASH 2010. Abstract 114.

Romidepsin in Relapsed/Refractory PTCL

 ORR (by IRC): 26% (34/130)
 CR: 13%
 Median duration of response: 12 months
 Median duration of CR: not reached (<1 to 26.3+
months)
 Median time to progression: 6 months
 Safety profile consistent with CTCL studies
– Most common grade ≥3 AEs: thrombocytopenia (24%);
neutropenia (20%)

Coiffier B, et al. ASH 2010. Abstract 114.

Treatment-Related Adverse Events
in ≥ 20% of Patients (N = 131)
At least one TEAE

Nausea

Infection

Fatigue

Vomiting

Thrombocytopenia

Diarrhea

Pyrexia

Neutropenia

Constipation

Anorexia
Overall
Anemia
≥ Grade 3
Dysgeusia

Events with a missing toxicity grade are included.

Hematologic Toxicities ≥ 5% (N = 131)

Grade ≥ 3;
Drug-
All Grade ≥ 3 Drug- D/C
Related
Related

Thrombocytopenia* 38% 24% 37% 23% 2%

Neutropenia† 30% 20% 29% 18% 1%

Anemia 24% 10% 20% 5% 0

Leukopenia 12% 6% 12% 6% 1%

*9 patients (7%) had a bleeding event [3 pts ≥ Grade 3]. 6/9 related to thrombocytopenia
† Febrile neutropenia reported as AE in 5 patients (4%). Growth factors used in 13% of patients

D/C, events leading to discontinuation.

39

Brentuximab Vedotin (SGN-35) in ALCL

 3 components:
– Chimeric antibody SGN-30
– Synthetic analog (MMAE) of the
antitubulin agent dolastatin 10
– Stable drug linker
 Proposed mechanism of action
– Binds to CD30
– Internalized into the tumor cell
– MMAE is released G2/M cell cycle

– Tumor cell undergoes G2/M arrest and
apoptosis

phase cell cycle arrest and
apoptosis
 Preclinical activity observed both
in vitro and in vivo

ADC=antibody-drug conjugate; MMAE= monomethylauristatin E.
Reproduced with permission from Seattle Genetics, Inc.; Pro. 2009 ASCO Educational Book.
Alexandria, VA: American Society of Clinical Oncology. 2009;486; Younes. EHA. 2009 (abstr 0503).

Brentuximab Vedotin in Relapsed/ Refractory
Systemic ALCL

N=58 Primary endpoint
• Single-arm • ORR by independent
• Phase II Brentuximab vedotin 1.8 review
• Relapsed or mg/kg IV every 21 days Secondary endpoints
refractory • CR rate
systemic ALCL • Duration of response
• PFS
• OS
 Median age: 52 years (range, 14-76)
 Median of 2 prior regimens (range, 1-6)
 62% refractory to frontline therapy

Shustov AR, et al. ASH 2010. Abstract 961.

Brentuximab Vedotin: Key Response Results

N=58 IRF Investigator
Overall response rate (95% CI) 86% (75, 94) 81% (69, 90)
Complete remission 53% 59%
Partial remission 33% 22%
Stable disease 3% 9%
Progressive disease 5% 3%
Histologically ineligible 3% 3%
Not evaluable 2% 3%
Outcomes
Median duration of OR (95% CI) Not reached (36, −) 36 weeks (31, −)
Median duration of CR (95% CI) Not reached (36, −) Not reached (35, −)
Median PFS (95% CI) Not reached 41 weeks (23, −)
Median OS Not reached

Common Adverse Events*

Preferred Term All Grades
Nausea 38%
Peripheral sensory neuropathy 38%
Fatigue 34%
Pyrexia 33%
Diarrhea 29%
Neutropenia 21%
Rash 21%
* Events of any relationship occurring in ≥20% of patients, N=58

1.0 Primary Cutaneous
0.9 ALCL
0.8

0.7
Proportion

0.6

0.5 ALCL, ALK+
0.4

0.3 ALCL, ALK-
0.2

0.1
Transformed MF PTCL-NOS
0.0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time
PTCL, if CD30+ in > 80% of cells-worse prognosis
HTLV-1/ATLL may be CD30+ .

MF with large cell transformation will be CD30+

Vose, Weisenburger, et al, International T-cell Classification Project

Bendamustine in T-cell lymphoma (BENTLY Trial)

N=60
• Multicenter,
single-arm,
Bendamustine 120 If no PD:
phase II study
mg/m2 IV on Days 1,2 Additional 3 cycles
• Relapsed or
every 3 weeks for 3 bendamustine
refractory T-
cycles
cell lymphoma
• ≤ 3 prior lines
chemotherapy Primary endpoint
• ORR (IWC 1999 criteria)
T-cell lymphoma subtypes (n):
 AILT (24) Secondary endpoints
 PTCL-NOS (17) • Safety, tolerability
 ALCL (4) • Duration of response
 EATL (1) • PFS
 MF (1) • OS

Damaj G, et al. 11th ICML; Lugano 2011. Abstract 126.

Bendamustine in Relapsed/ Refractory T-cell
Lymphoma

 ORR: 42%; CR: 23%
 Median DOR: 5.5 months
– Median duration of CR: 11.9 months
 Most common grade 3/4 adverse events:
– Neutropenia (49%)
– Thrombocytopenia (36%)
– Infections (34%)

Damaj G, et al. 11th ICML; Lugano 2011. Abstract 126.

Phase II Trial: Lenalidomide in
Relapsed/Refractory TCL

N=24 Lenalidomide 25 mg PO Primary endpoint
• T-cell lymphoma QD on days 1-21 of each • ORR
(other than MF) 28-day cycle Secondary endpoints
• WHO PS ≤3 Until disease • PFS
• Previously treated or progression, death, or • OS
untreated but not unacceptable toxicity • Safety
suitable for standard
therapy

MF=mycosis fungoides.

Dueck G, et al. Cancer. 2010;116:4541-4548.

Lenalidomide in Relapsed/Refractory TCL

 ORR=30% (7/23)
 Median PFS = 96 days
 Median OS = 241 days (range, 8-696+ days)
 Common AEs
– Grade 4: thrombocytopenia (33%)
– Grade 3: neutropenia (20.8%), febrile neutropenia (16.7%), pain NOS (16.7%)

Histology No. CR PR ORR, %
ALCL 5 0 2 40
AITL 7 0 2 29
EATCL 1 0 0 0
HSTCL 1 0 0 0
PTCL 9 0 3 33

Dueck G, et al. Cancer. 2010;116:4541-4548.

Phase II Study of SMILE Chemotherapy in
Extranodal NK/T-cell Lymphoma, Nasal Type

• SMILE = Steroid (dexamethasone), Methotrexate, Ifosfamide,
L-asparaginase, Etoposide
• Patients with newly diagnosed stage IV or relapsed/refractory
ENKL (N=39)

 ORR 74%; CR 38%
 Highly myelosuppressive:
– Grade 3/4 neutropenia: 8%/92%
– Grade 3/4 leukopenia: 28%/72%
– Grade 3/4 infection: 41%/13%
– Lymphocyte count ≥ 500/mm3 added to eligibility criteria after first 2 patients
died from infection


Yamaguchi M, et al. ASCO 2010. Abstract 8044.

Can we move new therapies upfront to change
standard treatment paradigms?
•Incorporating new therapies
•Adding to existing regimens may be limited (very active single agent)
•Otherwise novel approaches
•Novel ways to incorporate new drugs-can be done now
•Completely novel regimens-will take time

CHOP SGN-35 or similar

New Drug New Drug New Drug Etc.

Combination Alternating or Maintenance

A Multi-center, Randomized, Phase 3 Study of Sequential
Pralatrexate Versus Observation in Patients PTCL Who Have
Not Progressed Following Initial Treatment with CHOP-based
Chemotherapy

R
R Pralatrexate
A
E Maintenance
PTCL-see eligibility N
“CHOP” S D
No prior therapy (1
x 6 cycles T O
cycle CHOP-like CR, PR
allowed) A M
Appropriate for CHOP G I
based treatment I observation
Z
N E
G
2:1
At progression-
Co-Primary Endpoint OS/PFS PD not eligible treat as physician
discretion,
including PDX

Managing T-Cell Lymphoma

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