Tag: T-cell lymphoma

Weill Cornell Medicine – 2016 ASH Abstracts

2016 has been another productive year for research in the Lymphoma Program at Weill Cornell Medicine. Listed below are the abstracts we were involved in whole or in part to be presented at this year’s 58th Annual Meeting of the American Society of Hematology (ASH).

Look to this space for more information about developments during the ASH meetings this December 3-6.

CLL/SLL

60 – Acalabrutinib Monotherapy in Patients with Richter Transformation from the Phase 1/2 ACE-CL-001 Clinical Study

188 – The Landscape of Dynamic Genetic Changes in Ibrutinib-Treated CLL

192 – Outcome of Patients with Complex Karyotype in a Phase 3 Randomized Study of Idelalisib Plus Rituximab for Relapsed Chronic Lymphocytic Leukemia

233 – Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia

304 – Targeting Cellular Metabolism and Survival in Chronic Lymphocytic Leukemia and Richter Syndrome Cells By a Novel NF-Kb Inhibitor

621 – Phase 1 Study of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients with CD20+ B-Cell Malignancies Previously Treated with CD20-Directed Antibody Therapy

638 – Acalabrutinib Monotherapy in Patients with Ibrutinib Intolerance: Results from the Phase 1/2 ACE-CL-001 Clinical Study

642 – Venetoclax (VEN) Monotherapy for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapsed after or Were Refractory to Ibrutinib or Idelalisib

969 – Mutations in NOTCH1 PEST Domain Orchestrate CCL19-Driven Homing of Chronic Lymphocytic Leukemia (CLL) Cells By Modulating the Tumor Suppressor Gene DUSP22

1047 – Single Cell Bisulfite Sequencing Defines Epigenetic Diversification in Chronic Lymphocytic Leukemia

3705 – A Retrospective Analysis of Pneumocystis Jirovecii Pneumonia Infection in Patients Receiving Idelalisib in Clinical Trials

4349 – FAT1 Mutations Influence Time to First Treatment in Untreated CLL

Diffuse Large B-Cell Lymphoma

469 – Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303

473 – A Multicenter Open-Label, Phase 1b/2 Study of Ibrutinib in Combination With Lenalidomide and Rituximab in Patients With Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

734 – EZH2 Enables the Proliferation of Germinal Center B Cells and DLBCL through a Rb-E2F1 Positive Feedback Loop Involving Repression of CDKN1A

837 – RNA Interference Screen Implicates TNFAIP3 and FOXO1 in MALT1 Inhibition Resistance

1045 – AICDA Introduces Epigenetic Plasticity in Germinal Center-Derived Lymphomas and Accelerates Lymphomagenesis

1087 – Integrative Genetic and Clinical Analysis through Whole Exome Sequencing in 1001 Diffuse Large B Cell Lymphoma (DLBCL) Patients Reveals Novel Disease Drivers and Risk Groups

3045 – Ribavirin, an eIF4E Inhibitor, As a Potential Anti-Lymphoma Therapeutic – Preclinical and Early Clinical Data

Follicular Lymphoma

616 – Continued Excellent Outcomes in Previously Untreated Follicular Lymphoma Patients after Treatment with CHOP Plus Rituximab or CHOP Plus (131) Iodine-Tositumomab – Long Term Follow-up of Phase III Randomized Study SWOG S0016

1217 – Ibrutinib As Treatment for Chemoimmunotherapy-Resistant Patients with Follicular Lymphoma: First Results from the Open‑Label, Multicenter, Phase 2 DAWN Study

1804 – Ibrutinib Combined with Rituximab in Treatment-Naive Patients with Follicular Lymphoma: Arm 1 + Arm 2 Results from a Multicenter, Open-Label Phase 2 Study

2953 – Early Relapse of Follicular Lymphoma after Rituximab-Based Biologic Doublet Upfront Therapy Is Associated with Increased Risk of Death: A Combined Analysis from CALGB Studies 50402, 50701 and 50803 (Alliance)

Hodgkin Lymphoma

924 – Subsequent Malignant Neoplasms Among Children and Adolescents with Hodgkin Lymphoma Treated with Response-Adapted Therapy: A Report from the Children’s Oncology Group Study AHOD0031

2949 – Hodgkin Lymphoma Patients Demonstrate Evidence of Systemic Perturbation of the Monocyte-Dendritic Cell Axis

3502 – Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) after Treatment with Nivolumab for Relapsed/Refractory Hodgkin Lymphoma

4088 – CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies

Mantle Cell Lymphoma

150 – A Phase I Trial of Ibrutinib Plus Palbociclib in Patients with Previously Treated Mantle Cell Lymphoma

610 – PIK3IP1 Inhibition of PI3K in G1 Arrest Induced By CDK4 Inhibition Reprograms MCL for Ibrutinib Therapy

1096 – Lymphoid-like Environment, Which Promotes Proliferation and Induces Resistance to BH3-Mimetics, Is Counteracted By Obinutuzumab in MCL:  Biological Rationale for the Oasis Clinical Trial

1786 – Effectiveness of Lenalidomide in Patients with Mantle Cell Lymphoma Who Relapsed/Progressed after or Were Refractory/Intolerant to Ibrutinib: The MCL-004 Study

2937 – PRMT5 Targets Tumor Suppressor Micro RNAs to Regulate Cyclin D1 and c-MYC in Mantle Cell Lymphoma

Non-Hodgkin Lymphoma

536 – Toxicities and Related Outcomes of Elderly Patients (pts) (≥65 Years) with Hematologic Malignancies in the Contemporary Era (Alliance A151611)

756 – Molecular Basis of Ibrutinib Resistance in Waldenstrom’s Macroglobulinemia

1213 – Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study

4651 – Autologous Transplantation As Consolidation for High Risk Aggressive T-Cell Non-Hodgkin’s Lymphoma: A SWOG S9704 Intergroup Trial Subgroup Analysis

T-Cell Lymphoma

461 – Novel Long Non Coding RNA Blackmamba Is Associated to ALK- anaplastic Large Cell Lymphoma

621 – Phase 1 Study of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients with CD20+ B-Cell Malignancies Previously Treated with CD20-Directed Antibody Therapy

2741 – VAV1 Activating Mutations and Translocations in Peripheral T-Cell Lymphomas

4096 – Molecular Subgroups of Peripheral T-Cell Lymphoma Evolve By Distinct Genetic Pathways 

New Clinical Trial: Phase 2 Study of High Dose Chemotherapy with Autologous Stem Cell Transplant followed by Maintenance Therapy with Romidepsin for the Treatment of T-cell Lymphoma

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with T-cell lymphoma. The study sponsor is Memorial Sloan Kettering Cancer Center, and the principal investigator at Weill Cornell is Jia Ruan, M.D., Ph.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 16 and older.
  • T-cell non-Hodgkin lymphoma (NHL).
  • Complete or partial response to prior therapy.
  • Eligible for stem cell transplant.
  • No prior autologous or allogenic transplant.

Study Details

This clinical trial is for men and women with T-cell non-Hodgkin lymphoma. The purpose of the study is to test the benefit of a chemotherapy drug called romidepsin in men and women who have undergone autologous stem cell transplant.

Romidepsin has been FDA-approved for treating relapsed T-cell lymphoma. It is possible that in people who are at risk of their disease coming back (relapse), romidepsin could be used to prevent or delay the T-cell lymphoma from returning. The study will determine if giving romidepsin after the autologous stem cell transplant is safe and will prevent or delay the T-cell lymphoma from returning.

Participants will receive high dose chemotherapy followed by the stem cell transplant. Between 42 and 80 days after the transplant, participants will receive their first dose of romidepsin via infusion. Participants will continue to receive romidepsin every other week until 1 year after the stem cell transplant. If a participant’s disease has not progressed 1 year after the transplant, he/she will continue on romidepsin for another year.

Integrin αvβ3 Presents a Possible Therapeutic Target for Patients with T-cell Lymphomas

lecBy Leandro Cerchietti, MD

Malignant T-cell proliferation, survival, and drug resistance are dependent on a combination of external stimuli delivered by the micro-environment. Previous research has shown that the transmembrane receptor integrin αvβ3 plays a crucial role in mediating the interaction of T-cell lymphoma (TCL) cells with external signals. Integrin αvβ3 ligands include extracellular matrix-associated signaling proteins and soluble factors such as thyroid hormones (TH). Having previously shown that TH stimulate the proliferation of TCL through complimentary intracellular pathways involving the αvβ3 integrin, we hypothesized that targeting integrin αvβ3 could represent a novel strategy in treating TCL patients in an abstract presented during ASH.

In determining whether αVβ3 integrin is of therapeutic benefit for TCL, xenografts were developed in SCID mice using CUTLL1 cells transfected with si-control, si-αV and si-β3, and monitored tumor growth and angiogenesis. CUTLL1 was found to transfect with si-αV and si-β3 developed significant smaller tumors than si-control. The translational impact of this strategy was determined through the effect of cilengitide, a selective αVβ3 integrin inhibitor in phase 3 for glioma, in pre-clinical models of PTCL-NOS,  ALCL-ALK+ and  ALCL-ALK-. Similarly to si-αV and si-β3 treated mice, the anti-lymphoma effect of cilengitide correlated with lower levels of angiogenesis and NFkB activation.

This allowed us to elucidate the mechanisms by which integrin αvβ3 activation increases TCL proliferation through the activation of pro-survival pathways in malignant T-cells, while promoting angiogenesis. In the course of our research we also found that the genetic and pharmacological targeting of integrin αvβ3 induces an anti-lymphoma effect in TCL, including ALCL-ALK + and ALCL-ALK- PDT models obtained from treatment refractory patients. Both of these findings present potentially new therapeutic targets for the treatment of patients with T-cell lymphoma.

%d bloggers like this: