1. Julie M. Vose, M.D. University of Nebraska Medical Center
Chemotherapy for PTCL
Julie M. Vose, M.D.
University of Nebraska Medical Center

2. Overall Survival PTCL-NOS Cases by IPI Test: p<0.001 Proportion
1.0
Test: p<0.001
0.9
0.8
0.7
0.6
Proportion
0.5
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
IPI
CENSOR
FAIL
TOTAL
MEDIAN
0/1 36 47 83
5.03 2 36 67
103
2.1 3 20 53 73
1.41
4/5 9 38 47
0.68

3. PTCL-NOS Cases by Anthracycline Initial Tx
Overall Survival
PTCL-NOS Cases by Anthracycline Initial Tx
1.0
0.9
Test: p=0.14
0.8
0.7
0.6
0.5
Proportion
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Anthracycline as part of initial tx
CENSOR
FAIL
TOTAL
MEDIAN
yes 98
173
271
2.1 no 14 34 48
1.57

4. PTCL-NOS Cases by Carbo/Cisplatin Initial Tx
Overall Survival
PTCL-NOS Cases by Carbo/Cisplatin Initial Tx
1.0
0.9
Test: p=0.46
0.8
0.7
0.6
0.5
Proportion
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Carbo/Cisplatin as part of initial tx
CENSOR
FAIL
TOTAL
MEDIAN
yes 2 6 8
2.01 no
110
200
310
2.1

5. PTCL - Therapy Addition of novel agents to induction therapy
High-dose chemotherapy and autologous stem cell transplant in PR1/CR1
Improved /novel agents for salvage therapy
? Allogeneic stem cell transplantation to take advantage of GVL effect

6. Receptor-directed Therapy in T cell Lymphoma
CD25
(IL-2Ra
CD3
CD52
CD122
(IL-2R/IL-15Rb
CD4
CD30
CD2
Malignant
or Activated
T Cell

7. ONTAK + CHOP First-line Treatment of PTCL
Phase II, Multicenter, Open-label, Single- arm
48 subsites
Up to 50 newly diagnosed patients
Regimen
ONTAK 18 mcg/kg/d Days 1 & 2, followed by CHOP Days 3-7 of each cycle x 6 cycles
Objectives
ORR, TTP, Safety
Potential amendment
Consolidation ONTAK in patients who achieve CR

8. DA-EPOCH-Alemtuzumab in Untreated Peripheral T-Cell Lymphoma
Study Rationale
Chemotherapy/monoclonal antibody combinations
have improved survival in Diffuse Large B-Cell
Lymphoma
EPOCH-A schedule 1 3 6 9 12 15 18
Dose level 1 30 mg
Dose level mg
Dose level 3 90 mg
EPOCH:
Alemtuzumab:
NCI

9. A Phase II Study of Alemtuzumab in Combination with CHOP and ESHAP as a First-Line Treatment in PTCL
Tanin Intragumtornchai, Udomsak Bunvorasate, Thanyaphong NaNakorn, Ponlapat Rotnuckkarin
Division of Hematology
Department of Medicine Faculty of Medicine
Chulalongkorn University, Bangkok, Thailand

10. M = MabCampath 30 mg sc. D1-3; C= CHOP;
Treatment Schedule C E
M = MabCampath 30 mg sc. D1-3; C= CHOP;
E = ESHAP M

11. PI: Barbara Pro, MD M.D. Anderson Cancer Center
A Phase II Study of SGN-30 in Combination with CHOP in Anaplastic Large Cell Lymphoma NCI-CTEP
PI: Barbara Pro, MD
M.D. Anderson Cancer Center

12. Study Summary Within 4 weeks of initiation of therapy CTs H &P PS
BM biopsy
PET scan
SGN mg/kg
Weekly for 3 weeks
Restaging
SGN-30 + CHOP q 21 days
6-8 cycles
Correlative studies
Serum CD30 before 1st dose of SGN-30
Ln Bx before the 1st and after the 3rd dose of SGN-30

13. Siplizumab in CD2 Lymphoproliferative Disease
Deirdre O’Mahony, MD
National Cancer Institute

14. Safety Evaluation for Dose Escalation
Cohort Phase I MEDI-507
MEDI-507 Dosing
Follow-up 1 2 3 4 5 6 7 8 9 10 12 14 16
Weeks
Disease Evaluation
Disease Evaluation
Disease Evaluation
Safety Evaluation for Dose Escalation
*MEDI-507 administered week 1,3 and weekly thereafter for total 16 treatments or until PD, toxicity, or other reasons

15. Safety Evaluation for Dose Escalation
Cohort 1-7 Phase I MEDI-507
MEDI-507 Dosing
Follow-up 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
LTFU
Weeks
Disease Evaluation
Disease Evaluation
Disease Evaluation
Disease Evaluation
Safety Evaluation for Dose Escalation
*MEDI-507 received over 2-3 consecutive days per week (depending on cohort), every other week for 16 weeks or until PD, toxicity, or other reasons

16. Safety Evaluation for Dose Escalation
Cohort Phase I MEDI-507
MEDI-507 Dosing
Follow-up 1 2 3 4 5 6 7 8 9 10 12 14 16
Weeks
Disease Evaluation
Disease Evaluation
Disease Evaluation
Safety Evaluation for Dose Escalation
*MEDI-507 administered week 1,3 and weekly thereafter for total 16 treatments or until PD, toxicity, or other reasons

17. GELA (A. Delmer, B. Coiffier) Genetic randomisation
GELA LNH T 1st line
V-ACVBP – Velcade
GELA (A. Delmer, B. Coiffier)
18 – 60 yrs
R A I L
(GELA)
C. Haioun
CHOP - Mab-CHOP
Intergroup – Schering
(NLG ) F. D’Amore
60 – 80 yrs
Auto/allo
< 60 yrs
Genetic randomisation
In preparation
« CHOP »
« CHOP »
Auto
Mini-Allo
German High Grade
(N. Schmitz)

18. Gemcitabine
Analog of ara-C with > membrane permeability and affinity for deoxycytidine kinase   cellular uptake
Self-potentiating mechanism of action  enhanced accumulation and prolonged retention within malignant cells  inhibits DNA synthesis
Expanded anti-tumor activity, including in solid tumors and lymphoma.

19. GDP GDP = gemcitabine (D1, D8), dexamethasone (D1-4), cisplatin (D1)
- outpatient administration
- in vitro evidence of synergy with cisplatin
NCIC 2 Ph II trials
Relapsed aggressive NHL RR 53%
Relapsed HL RR 70%

20. Primary Treatment of PTCL with GDP
Study proposal: Primary therapy of PTCL with GDP
Eligibility: all patients with advanced stage* PTCL and limited stage PTCL with > 2 IPI RFs
Histology: PTCLUS, AILT, ALK neg ALCL, ETTL, HSTCL, SCPTCL
Exclude: Cut ALCL, ALK pos ALCL and NK/T cell lymphoma to receive primary radiotherapy
* Advanced = stage III/IV, bulky, B sxs

21. METHOTREXATE = Pralatrexate (PDX) = HC H C – CH2 N N H2N H H H N N CH21 8 H
METHOTREXATE H N 4 5 N 9
CH2
NH 2 O
COO- = 10
H3C N
C - N - C - CH2 - CH2 - COO- H H N N
H2N H 1 8
Pralatrexate (PDX) H H N 4 5 N 9 CH
NH 2 O
COO-
H3C = 10
C - N - C - CH2 - CH2 - COO- HC H H
H C – CH2

22. TUMOR CELL Compared to MTX PDX more efficiently enters tumor cells
cMOAT/
MRP
ATPase
RFC-1
Plasma membrane
ATP
PDX
PDX
(& Natural
Folates)
PDX
FPGS
PDX(G)n
ATP + MgCl2
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 retained (FPGS)

23. PTCL-NOS Cases by Stem Cell Transplant
Overall Survival
PTCL-NOS Cases by Stem Cell Transplant
1.0
0.9
Test: p=0.0076
0.8
0.7
0.6
0.5
Proportion
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time
Hi-dose therapy (transplant)
CENSOR
FAIL
TOTAL
MEDIAN
yes 21 27 48
3.5 no 63
148
211
1.95

24. PTCL-NOS Cases by Transplant Reason
Failure-free Survival
PTCL-NOS Cases by Transplant Reason
1.0
0.9
Test: p<0.001
0.8
0.7
0.6
0.5
Proportion
0.4
0.3
0.2
0.1
0.0 1 2 3 4 5 6 7 8 9 10 11
Time
Transplant reason
CENSOR
FAIL
TOTAL
MEDIAN
inital tx 8 15 23
1.46
subseq. to recur. 24 24
0.71

25. Auto PSC for PTCL and ALCL: UNMC Anaplastic CR2+ / Rel 1 (n=15). . 9 . 8
PTCL CR2+ / Rel 1 (n=8) . 7 . 6
Anaplastic CR2+ / Rel 1 (n=15)
PFS Probability . 5 . 4
PTCL CR1 / PR1 (n=18) . 3 . 2 . 1 1 2 2 4 3 6 4 8 6
Months

26. Auto PSC for PTCL and ALCL: UNMC Anaplastic CR2+ / Rel 1 (n=15).
Anaplastic CR2+ / Rel 1 (n=15) . 9 . 8 . 7 . 6
PTCL CR1 / PR1 (n=18)
Survival Probability . 5 . 4 . 3
PTCL CR2+ / Rel 1 (n=8) . 2 . 1 1 2 2 4 3 6 4 8 6
Months

27. Future for PTCL Therapy
Addition of novel agents to induction therapy
New agents for salvage therapy
Directed therapy by IHC or gene expression?
? Stem cell transplantation in CR1
Allogeneic stem cell transplantation