Weill Cornell Medicine Lymphoma Program Related Abstracts at ASH 2015

2015 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 57th Annual Meeting of the American Society of Hematology (ASH) in December.

Look to this space for future updates about lymphoma related developments from ASH 2015.

B-cell Lymphomas

434 – A Chromatin Reader That Acts As a Key to Lock in and Coordinate Recruitment of Transcription Factors and a Novel Polycomb Complex to Bivalent Chromatin Thus Driving Formation of Germinal Centers and B-Cell Lymphomas

2427 – Transcriptome Sequencing Reveals Thousands of Novel Long Non-Coding RNAs in B-Cell Lymphoma

2756 – Scavenger Receptor Type B1 Is Essential for High Density Lipoprotein Nanoparticle Induced B-Cell Lymphoma Cell Death

Burkitt ’s lymphoma

592 – Targeting the Hsp90 Oncoproteome in Burkitt Lymphoma

CLL/SLL

831 – The Bruton Tyrosine Kinase (Btk) Inhibitor ACP-196:  Marked Activity in Relapsed/Refractory CLL with a Favorable Safety Profile

833 – Outcome of Ibrutinib Treatment by Baseline Genetic Features in Patients with Relapsed or Refractory CLL/SLL with del17p in the Resonate-17 Study

1728 – SLAMF1/CD150 Activates Autophagy in Chronic Lymphocytic Leukemia Cells, Modulating Chemotaxis and Responses to Therapy

2952 – Patterns of Lymphocytosis in Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Treated with Idelalisib

4145 – Adenosine Signaling Mediates Hypoxic Responses in the Chronic Lymphocytic Leukemia Microenvironment

4153 – Analysis of Prognostic Factors Predictive of Complete Response (CR) to Ibrutinib in Patients with CLL/SLL

DLBCL

811 – Randomized Phase 2 Open-Label Study of R-CHOP ± Bortezomib in Patients (Pts) with Untreated Non-Germinal Center B-Cell-like (Non-GCB) Subtype Diffuse Large Cell Lymphoma (DLBCL): Results from the Pyramid Trial (NCT00931918)

2739 – Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab Following Standard Chemotherapy for Patients with Intermediate-High/High Risk Diffuse Large B-Cell Lymphoma (DLBCL) – Final Results

Follicular Lymphoma

334 – Interfollicular CD10 Expression and Follicular PD1 Tumor-Infiltrating Lymphocytes As Biologic Risk Factors in Patients with Previously Untreated Follicular Lymphoma Receiving Rituximab-Based Biologic Therapy: An Alliance Correlative Science Study (CALGB 50901, 50402, 50701, 50803, 50401)

471 – Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma (Alliance 051103)

2744 – Activity of Idelalisib in High-Risk Follicular Lymphoma with Early Relapse Following Front Line Immunochemotherapy

Hodgkin Lymphoma

519 – Post Transplant Outcome of a Multicenter Phase II Study of Brentuximab Vedotin As First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT

578 – Initial Results of US Intergroup Trial of Response-Adapted Chemotherapy or Chemotherapy/Radiation Therapy Based on PET for Non-Bulky Stage I and II Hodgkin Lymphoma (HL) (CALGB/Alliance 50604)

2636 – Outcomes in Adolescents and Young Adults (AYA) with Hodgkin Lymphoma (HL) Treated on US Cooperative Group Protocols: An Adult Intergroup (E2496) and Children’s Oncology Group (COG AHOD0031) Comparative AnalysisClinically Relevant Abstract

2639 – The Landscape of microRNA Expression in HIV and Non-HIV Associated Classical Hodgkin Lymphoma through Next Generation Sequencing

Mantle Cell Lymphoma

337 – Bortezomib Maintenance (BM) Versus Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): CALGB (Alliance)50403

518 – Pre-Transplant R-Bendamustine Induces High Rates of Minimial Residual Disease in MCL Patients: Updated Results of S1106: US Intergroup Study of a Randomized Phase II Trial of R-HCVAD Vs. R-Bendamustine Followed By Autologous Stem Cell Transplants for Patients with Mantle Cell Lymphoma

4527- Clinical Impact of Internet-Based Tools to Help Guide Therapeutic Decisions for Mantle Cell Lymphoma (MCL)

Marginal Zone Lymphoma

1543  Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL)

Non-Hodgkin Lymphoma

258- Safety, Efficacy, and Determination of the Recommended Phase 2 Dose for the Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330)

2741 – Phase II Trial of Ofatumumab (OFA) in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL): CALGB 50901 (Alliance)

3961 – Long-Term Outcomes, Secondary Malignancies, and Stem Cell Collection Following Bendamustine in Patients with Previously Treated Indolent Non-Hodgkin Lymphoma

T-Cell Lymphoma

341 – First Multicenter, Randomized Phase 3 Study in Patients (Pts) with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL): Alisertib (MLN8237) Versus Investigator’s Choice (Lumiere trial; NCT01482962)

1451 – Assessment of T-Cell Receptor Repertoire and Clonal Expansion in Peripheral T-Cell Lymphoma Using RNA-Seq Data

Waldenstrom’s Macroglobulinemia

703 – VLX1570, a First in Class Dub Inhibitor, Modulates BCR Signaling and CXCR4 Expression and Demonstrates Significant In Vivo Antitumor Activity in a Murine Model of Human Waldenstrom Macroglobulinemia

New Drug Combination Displays Promise for the Treatment of Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma that primarily affects elderly patients. Due to the age of these patients and associated medical conditions, they are often less able to tolerate chemotherapy regimens. Still those patients who are eligible for chemotherapy frequently relapse, and require further treatment. However, clinicians in the Lymphoma Program at Weill Cornell Medicine recently published results from a clinical trial that combined the non-chemotherapy alternatives of lenalidomide and rituximab as an initial treatment for patients with MCL.

These findings were published online Nov. 4 and in the Nov. 5 print issue of the New England Journal of Medicine. They demonstrate that the combination of lenalidomide and rituximab provides an effective alternative to chemotherapy for MCL patients. Over 90% of patients enrolled in the trial responded to the therapy, with long term outcomes at the 2 year mark remaining steady in 85% of patients. During treatment patients maintained a high quality of life and were able to participate in daily activities like work, travel, and standard social activities.

The lead author of the study Dr. Jia Ruan an associate professor of clinical medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. She commented on the results,

 “For patients, their quality of life was preserved or improved, and that’s a huge step up from regular chemotherapy…With this frontline treatment, we were able to achieve a very high quality and durable response rate without needing to use chemotherapy. It’s very meaningful for the patients who have always been told that their disease is without a cure.”

She continued on the benefits of this  treatment combination when compared to other treatments,

“Conventional, intensive treatment may be out of reach or undesirable for many MCL patients, who often receive less intensive or palliative care that is of limited benefit. This inspired us to look for a less toxic, biological option with novel drugs that could be easily administered and more widely applicable.”

The senior author of the study Dr. John Leonard, a professor of medicine, the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at the Joan and Sanford I. Weill Department of Medicine, associate dean for clinical research, and associate director of clinical trials at the Meyer Cancer Center at Weill Cornell Medicine commented on the trial,

“I’m inspired by the fact that patients are enthusiastic about this approach. I’m also excited that lymphoma physicians are thinking out of the box, that many in the community now think that a non-chemotherapy-based paradigm with novel agents is something important to take forward and more broadly assess.”

Clinical trials like this exemplify the bench to bedside approach taken in the Lymphoma Program at Weill Cornell Medicine. Look to this space for future updates on MCL, and treatment with this new combination. A listing of available clinical trials for MCL can be found on our Joint Clinical Trials website.

New Findings May Play Role in Development of Future DLBCL Treatments

Researchers from Weill Cornell Medicine led by Dr. Olivier Elemento, recently published results announcing the discovery of thousands of new genes from human samples of lymphoma. Known as IncRNAs these genes produce long non-coding RNAs and are involved in gene regulation. The IncRNAs appear to control whether other genes make proteins. The discovery of these genes could underline the processes of gene regulation that drives lymphomas, while in the future leading to possible targets for new  diffuse large B-cell lymphoma therapies.

“These genes produce long non-coding RNAs, known as lncRNAs. Unlike RNA that produces proteins that enable the body to do its work, the lncRNA appear to switch on — or off — other genes that make proteins, researchers say. They counted 2,632 different forms of these unusual RNA molecules. They also found a substantial number of the same or similar lncRNAs in canine lymphoma.”

The study’s senior author, Dr. Olivier Elemento commented,

“While we don’t know precisely what these molecules are doing, the fact that the majority — about two-thirds — of the long non-coding RNAs we found are expressed exclusively in lymphoma, and that many are found in both human and dog lymphoma, tells us that they are likely playing fundamental roles in this cancer…”

Findings like these exemplify the bench to bedside approach in the Lymphoma Program at Weill Cornell Medicine. Look to this space for future updates on this topic and other advances in the treatment of lymphoma. A full listing of available clinical trials for DLBCL lymphoma can be found on our Joint Clinical Trials website.