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Discover the latest advancements in Peripheral T-Cell Lymphoma (PTCL) treatments and survival outcomes analyzed by Dr. Julie M. Vose from the University of Nebraska Medical Center. Explore the impact of chemotherapy regimens, individualized testing, and novel agents on patient prognosis and overall survival rates for PTCL subtypes. Stay informed on cutting-edge therapies and research efforts in the field of PTCL management.
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Chemotherapy for PTCL Julie M. Vose, M.D. University of Nebraska Medical Center
Overall Survival PTCL-NOS Cases by IPI Test: p<0.001 1.0 0.9 0.8 0.7 0.6 Proportion 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 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
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 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
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 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
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
CD2 CD25 (IL-2Ra CD52 Malignant or Activated T Cell CD122 (IL-2R/IL-15Rb CD3 CD30 CD4 Receptor-directed Therapy in T cell Lymphoma
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
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 3 6 9 12 15 18 1 Dose level 1 30 mg Dose level 2 60 mg Dose level 3 90 mg EPOCH: Alemtuzumab: NCI
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
M M M M M C E E C E C M = MabCampath 30 mg sc. D1-3; C= CHOP; E = ESHAP Treatment Schedule
A Phase II Study of SGN-30 in Combination with CHOP in Anaplastic Large Cell LymphomaNCI-CTEP PI: Barbara Pro, MD M.D. Anderson Cancer Center
Study Summary Within 4 weeks of initiation of therapy CTs H &P PS BM biopsy PET scan SGN-30 12 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
Siplizumab in CD2 Lymphoproliferative Disease Deirdre O’Mahony, MD National Cancer Institute
Cohort 8-10 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
Cohort 1-7 Phase I MEDI-507 MEDI-507 Dosing Follow-up LTFU 1 2 3 4 5 6 7 8 9 10 11 13 14 15 16 12 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
Cohort 8-10 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
GELA LNH T1st 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 Genetic randomisation Auto/allo < 60 yrs In preparation « CHOP » « CHOP » Auto Mini-Allo German High Grade (N. Schmitz)
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.
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%
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
N N H2N H 1 8 METHOTREXATE H H N 4 5 N 9 CH2 NH 2 COO- O = 10 H3C C - N - C - CH2 - CH2 - COO- N H H N N H2N H 1 Pralatrexate (PDX) 8 H H N 4 5 N 9 CH NH 2 COO- O H3C = 10 C - N - C - CH2 - CH2 - COO- HC H H H C – CH2
TUMOR CELL cMOAT/ MRP ATPase RFC-1 Plasma membrane ATP PDX PDX PDX (& Natural Folates) 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)
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 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
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 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. 0 24 24 0.71
Auto PSC for PTCL and ALCL: UNMC 1 . 0 . 9 . 8 PTCL CR2+ / Rel 1 (n=8) . 7 . 6 Anaplastic CR2+ / Rel 1 (n=15) . 5 PFS Probability . 4 PTCL CR1 / PR1 (n=18) . 3 . 2 . 1 0 0 2 4 3 6 4 8 6 0 1 2 Months
Auto PSC for PTCL and ALCL: UNMC 1 . 0 Anaplastic CR2+ / Rel 1 (n=15) . 9 . 8 . 7 . 6 PTCL CR1 / PR1 (n=18) Survival Probability . 5 . 4 PTCL CR2+ / Rel 1 (n=8) . 3 . 2 . 1 0 0 2 4 3 6 4 8 6 0 1 2 Months
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