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 Clinical Trial: A Phase 2 Study to Evaluate the Efficacy & Safety of Copanlisib in Patients with Relapsed/Refractory MCL, who Failed Ibrutinib Treatment or Were Unable to Tolerate Ibrutinib

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with refractory MCL, who have failed ibrutinib treatment or were unable to tolerate ibrutinib. The study sponsor is the Bayer Corporation, and the principal investigator at Weill Cornell is Peter Martin M.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 18 and older with histologically confirmed MCL.
  • Ibrutinib as the last anti-cancer treatment.
  • Availability of fresh tumor tissue.
  • Detailed eligibility reviewed when you contact the study team.

Study Summary 

This clinical trial is for men and women with mantle cell lymphoma (MCL) who were previously treated for this disease and who failed ibrutinib treatment or were unable to tolerate ibrutinib treatment.

While treatment of MCL with ibrutinib has yielded promising efficacy, clinicians and researchers are reporting the development of ibrutinib resistance. Clinically, ibrutinib resistance leaves MCL patients without an established recourse for further treatment. Offering a treatment targeting a different pathway provides an opportunity to fulfill an unmet medical need in this patient population. In addition, some patients are unable to tolerate ibrutinib treatment, leaving them without an established therapeutic option after first-line treatment failure.

This is a single-arm, open-label phase 2a study to evaluate the efficacy and safety of copanlisib monotherapy in patients with MCL, who failed ibrutinib treatment or were unable to tolerate ibrutinib. Patients will receive copanlisib IV infusion at a starting dose of 60 mg as single agent on Days 1, 8 and 15 of each 28-day treatment cycle. Patients will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects. All patients, except for patients who object to follow-up data collection, will be followed for overall survival at least every 3 months during the survival follow-up period until death or until the end of study, whichever occurs first.