Video excerpts from a clinical investigator Think Tank held on July 19, 2013. Featuring perspectives from Drs Andrew M Evens, Christopher Flowers, Jonathan W Friedberg, Julie M Vose and Michael E Williams. (Video Program)
CE Disclosures and Faculty Information
TARGET AUDIENCE
This activity has been designed to meet the educational needs of medical oncologists, hematologists, hematology-oncology fellows and other healthcare providers involved in the treatment of hematologic cancers.OVERVIEW OF ACTIVITY
Non-Hodgkin lymphoma (NHL) comprises a heterogeneous group of lymphoproliferative disorders and is one of the most rapidly evolving fields in hematology and oncology. In contrast, Hodgkin lymphoma (HL) is a rarer disease that is relatively chemosensitive and often curable when treated appropriately. However, care for patients who do not respond to primary treatment or those with relapsed or refractory HL remains a significant challenge for oncology clinicians. Published results from ongoing clinical trials lead to the continual emergence of new therapeutic agents and changes in the use of existing treatments. To offer optimal patient care — including the option of clinical trial participation — practicing medical oncologists, hematologists and hematology-oncology fellows must be well informed of these advances. This program uses a roundtable discussion with leading clinical investigators to assist practicing clinicians in formulating up-to-date clinical management strategies for NHL, HL and chronic lymphocytic leukemia (CLL).LEARNING OBJECTIVES
- Develop an understanding of emerging efficacy and side-effect data with novel agents and combination regimens under evaluation for indolent and aggressive B-cell and T-cell NHL.
- Incorporate new therapeutic strategies into the best-practice management of HL.
- Develop an algorithm for the evaluation and treatment of newly diagnosed and relapsed/refractory CLL.
- Devise an evidence-based approach to the sequential systemic treatment of peripheral T-cell lymphoma.
- Use available research evidence and understand the controversies surrounding the use of CNS prophylaxis to guide treatment decision-making for patients with diffuse large B-cell lymphoma.
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Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education. We assess potential conflicts of interest with faculty, planners and managers of CME activities. Real or apparent conflicts of interest are identified and resolved through a conflict of interest resolution process. In addition, all activity content is reviewed by both a member of the RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.FACULTY — The following faculty (and their spouses/partners) reported real or apparent conflicts of interest, which have been resolved through a conflict of interest resolution process:
Andrew M Evens, DO, MSc
Professor of Medicine
Chief, Division of Hematology/Oncology
Tufts University School of Medicine
Director, Lymphoma Program
Leader, Clinical Sciences Program
Tufts Cancer Center
Boston, MassachusettsAdvisory Committee: Millennium: The Takeda Oncology Company, Seattle Genetics, Spectrum Pharmaceuticals Inc; Contracted Research: Millennium: The Takeda Oncology Company, ZIOPHARM Oncology Inc.
Christopher Flowers, MD, MS
Associate Professor of Hematology
and Medical Oncology
Emory School of Medicine
Winship Cancer Institute
Atlanta, GeorgiaConsulting Agreements: Celgene Corporation, Genentech BioOncology; Contracted Research: Abbott Laboratories, Janssen Pharmaceuticals Inc, Millennium: The Takeda Oncology Company, Sanofi, Spectrum Pharmaceuticals Inc.
Jonathan W Friedberg, MD, MMSc
Samuel Durand Professor of Medicine
Director, Wilmot Cancer Center
University of Rochester
Rochester, New YorkAdvisory Committee: Genentech BioOncology; Data and Safety Monitoring Board: Lilly.
Julie M Vose, MD, MBA
Neumann M and Mildred E Harris Professor
Chief, Division of Hematology/Oncology
Professor of Medicine
Nebraska Medical Center
Omaha, NebraskaContracted Research: Allos Therapeutics, AstraZeneca Pharmaceuticals LP, Celgene Corporation, Genentech BioOncology, GlaxoSmithKline, Incyte Corporation, Janssen Pharmaceuticals Inc, Millennium: The Takeda Oncology Company, Novartis Pharmaceuticals Corporation, OncoMed Pharmaceuticals Inc, Onyx Pharmaceuticals Inc, Pharmacyclics Inc, Sanofi, US Biotest Inc.
Michael E Williams, MD, ScM
Byrd S Leavell Professor of Medicine
Chief, Hematology/Oncology Division
University of Virginia School of Medicine
Charlottesville, VirginiaAdvisory Committee: Celgene Corporation, Genentech BioOncology, Janssen Pharmaceuticals Inc, Onyx Pharmaceuticals Inc; Consulting Agreements: Celgene Corporation, Millennium: The Takeda Oncology Company; Contracted Research: Allos Therapeutics, AstraZeneca Pharmaceuticals LP, Celgene Corporation, Genentech BioOncology, Gilead Sciences Inc, Millennium: The Takeda Oncology Company, Novartis Pharmaceuticals Corporation, Onyx Pharmaceuticals Inc, Pharmacyclics Inc.
MODERATOR — Dr Love is president and CEO of Research To Practice, which receives funds in the form of educational grants to develop CME activities from the following commercial interests: AbbVie Inc, Algeta US, Allos Therapeutics, Amgen Inc, ArQule Inc, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Biodesix Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Daiichi Sankyo Inc, Dendreon Corporation, Eisai Inc, EMD Serono Inc, Exelixis Inc, Foundation Medicine Inc, Genentech BioOncology, Genomic Health Inc, Gilead Sciences Inc, Incyte Corporation, Lilly, Medivation Inc, Merck, Millennium: The Takeda Oncology Company, Mundipharma International Limited, Novartis Pharmaceuticals Corporation, Novocure, Onyx Pharmaceuticals Inc, Prometheus Laboratories Inc, Regeneron Pharmaceuticals, Sanofi, Seattle Genetics, Spectrum Pharmaceuticals Inc and Teva Oncology.
RESEARCH TO PRACTICE STAFF AND EXTERNAL REVIEWERS — The scientific staff and reviewers for Research To Practice have no real or apparent conflicts of interest to disclose.
This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.
This activity is supported by educational grants from Genentech BioOncology/Biogen Idec, Lilly, Millennium: The Takeda Oncology Company, Seattle Genetics and Spectrum Pharmaceuticals Inc.
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Expiration date: November 2014
Acknowledge and close
(WIFI is recommended for best performance):
Hodgkin lymphoma (HL)
| Brentuximab vedotin as a bridge to transplant in HL | |
| Phase III trial of brentuximab vedotin as part of up-front treatment of HL | |
| Routine surveillance scanning in HL | |
| Case presentation: 34-year-old woman with relapsed HL who received brentuximab vedotin for progression after autotransplant | |
| Case presentation: 87-year-old woman with advanced-stage HL | |
| Case presentation: A young woman with bulky mediastinal HL and a BRCA germline mutation |
| Phase III CLL11 trial: Obinutuzumab combined with chlorambucil | |
| Lenalidomide in CLL | |
| Case presentation: 65-year-old physician with refractory CLL, autoimmune hemolytic anemia and 17p deletion |
| ECOG trial 2408 in high-risk FL evaluating BR + bortezomib as part of induction and lenalidomide + R as part of maintenance | |
| Radioimmunotherapy consolidation after R/chemo in indolent lymphoma | |
| Case presentation: 48-year-old woman with FL with disease progression after a prolonged response to R monotherapy as second-line therapy |
| Small-molecule B-cell receptor inhibitors: ibrutinib | |
| Case presentation: 77-year-old man with MCL with a complete response to BR now considering R maintenance or RIT consolidation |
| R-CHOP with lenalidomide in DLBCL | |
| Case presentation: 88-year-old man with DLBCL of the floor of the maxillary sinus | |
| Case presentation: 67-year-old man with “double-hit” DLBCL | |
| Case presentation: 28-year-old woman with primary mediastinal DLBCL |
| Belinostat, a new HDAC inhibitor with activity in relapsed/refractory peripheral TCL | |
| Case presentation: 76-year-old man who received pralatrexate for relapsed peripheral TCL NOS | |
| Case presentation: 61-year-old man who received brentuximab vedotin for relapsed ALK-negative anaplastic large cell lymphoma |
With 2 new agents approved this month (obinutuzumab and ibrutinib) and more molecules with unique mechanisms of action likely on the way (eg, idelalisib), oncologists now have a lot more to think about for many of their patients with B-cell neoplasias, Hodgkin lymphoma and peripheral T-cell lymphoma. To gain some perspective on where we are and most importantly, where we’re headed, 5 leaders in lymphoma clinical research joined us for a daylong gathering in Miami to review important data sets and present interesting cases from their practices. As we do following all of these unique events, video highlights are provided below, which now feature full transcripts and links to other relevant resources (click here for audio program).
Hodgkin Lymphoma (HL)
Brentuximab vedotin (BV) as a bridge to transplant in HL
Although the current label for this exciting antibody-drug conjugate specifies use in the postautotransplant space where it may be helpful in younger patients as a bridge to allotransplant, there is great interest in moving BV earlier — specifically as a bridge to autotransplant following first relapse. In this regard, the faculty commented on a Memorial data set reported in Lugano this summer documenting that 30% of patients achieved a PET-negative complete response with BV and successfully went on to autotransplant without chemotherapy (Moskowitz AJ et al. Proc ICML 2013;Abstract 141).
Phase III trial of BV as part of up-front treatment of HL
An initial study indicated that combining BV with ABVD resulted in excessive pulmonary toxicity but when added to AVD it was generally well tolerated, and this regimen is now the focus of an important Phase III up-front trial that will have great appeal to patients and physicians.
Routine surveillance scanning in HL
As with other lymphomas, credible evidence is accumulating that surveillance scans in asymptomatic patients with normal physical exams and laboratory data seem to add only cost, but many oncologists, including several faculty members, are reluctant to cut back or eliminate this type of imaging, particularly in potentially curative situations.
A 34-year-old woman with relapsed HL who received BV for progression after autotransplant
An 87-year-old woman with advanced-stage HL
A young woman with bulky mediastinal HL and a BRCA germline mutation
Chronic Lymphocytic Leukemia (CLL)
Phase III CLL11 trial: Obinutuzumab (OB) combined with chlorambucil (Chl)
Formerly known as GA101, this newly approved glycoengineered type II monoclonal antibody has been shown to have much greater binding affinity for CD20 than rituximab (R) while also enhancing antibody-dependent cell-mediated toxicity and direct cell death. In reviewing this agent at the think tank, discussion focused on the initial analysis of this trial presented at ASCO, but all agreed that the really juicy data will emerge at ASH next week when the comparison of OB/Chl to R/Chl will be unveiled, demonstrating what is expected to be significantly better efficacy with OB and similar tolerability other than more infusion reactions.
Lenalidomide (len) in CLL
All of the think tank faculty employ this immunomodulatory agent in relapsed/refractory CLL, and Dr Jonathan Friedberg in particular voiced his belief that len is a useful option that is often underused in clinical practice.
A 65-year-old physician with refractory CLL, autoimmune hemolytic anemia and 17p deletion
Follicular Lymphoma (FL)
ECOG trial 2408 in high-risk FL evaluating bendamustine/R (BR) + bortezomib as part of induction and len + R as part of maintenance
Faculty member Dr Andrew Evens is the principal investigator of this ongoing trial that was launched in 2010, but the rapid emergence of new agents in B-cell cancers raises the question of whether the results will be clinically meaningful when mature.
Radioimmunotherapy (RIT) consolidation after R/chemotherapy in indolent lymphoma
Dr Friedberg is anxiously awaiting results of his Phase II FL study incorporating both RIT and R maintenance after R/chemotherapy, but until those and other data are available most investigators and oncologists in practice favor R maintenance. Interestingly, panelist Julie Vose will substitute RIT consolidation for R maintenance in patients who have challenges coming to the clinic for infusions.
A 48-year-old woman with FL with disease progression after a prolonged response to R monotherapy as second-line therapy
Mantle-Cell Lymphoma (MCL)
Small-molecule B-cell receptor inhibitors: ibrutinib
The November 13th FDA approval of the oral Bruton’s tyrosine kinase inhibitor ibrutinib for patients receiving at least 1 prior treatment will clearly impact the sequential algorithm of this disease as the faculty members were already poised to use this fascinating agent prior to len or bortezomib.
A 77-year-old man with MCL with a complete response to BR now considering R maintenance or RIT consolidation
Diffuse Large B-Cell Lymphoma (DLBCL)
R-CHOP with len (R squared-CHOP) in DLBCL
In discussing the so-called “R squared-CHOP” regimen, the faculty agreed that len appears considerably more active in the activated B-cell subtype. An ongoing ECOG trial, ECOG-E1412, is evaluating this approach specifically in patients with newly diagnosed DLBCL.
An 88-year-old man with DLBCL of the floor of the maxillary sinus
A 67-year-old man with “double-hit” DLBCL
A 28-year-old woman with primary mediastinal DLBCL
T-Cell Lymphoma (TCL)
Belinostat, a new histone deacetylase (HDAC) inhibitor with activity in relapsed/refractory peripheral TCL
The faculty related that by indirect comparison the efficacy of belinostat seems similar to the other key HDAC inhibitor used in peripheral TCL, romidepsin, but one differentiating aspect of this agent is that it can be administered to patients with platelet counts as low as 50,000/µL, potentially making it useful in individuals who have received extensive prior treatment.
A 76-year-old man who received pralatrexate for relapsed peripheral TCL NOS
A 61-year-old man who received BV for relapsed ALK-negative anaplastic large cell lymphoma
Want to hear more about these and other developments in this scorching-hot field? Check out our ASH satellite symposium Friday afternoon, December 6th in New Orleans where a distinguished faculty panel will compare notes on how they currently sort out the rapidly increasing number of options for these patients.
Neil Love, MD
Research To Practice
Miami, Florida