In this, the fourth part (originally held July 5, 2011) of our eight-part online, integrated educational course, Drs Nikhil C Munshi and A Keith Stewart discuss recent advances in the treatment of MM. (Webinar)
CE Disclosures and Faculty Information
TARGET AUDIENCE
This activity is intended for hematologists, medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of MM.
OVERVIEW OF ACTIVITY
MM is a plasma cell neoplasm that accounts for approximately 10 percent of all hematologic cancer and carries with it the worst death/new cases ratio (3:4) among the whole of the blood cancer subtypes. The development of molecular-targeted agents and alternative chemotherapeutics for the treatment of MM has been the focus of extensive research and has resulted in the emergence of clinical scenarios in which multiple treatment options may be available. Controversy persists in several areas of patient care, such as selection of the optimal induction therapy for transplant and nontransplant candidates and post-transplant maintenance strategies. This program uses a review of recent ASCO papers and other relevant publications, faculty case presentations, Q&A and discussion of community practice patterns to assist practicing clinicians in the formulation of up-to-date and appropriate treatment strategies.
LEARNING OBJECTIVES- Integrate the results of new clinical research into the selection of optimal systemic therapy for patients with MM, both eligible and ineligible for stem cell transplant.
- Use evidence-based clinical and molecular factors to tailor maintenance treatment recommendations.
- Compare and contrast existing IMiDs and proteasome inhibitors with their experimental next-generation counterparts.
ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
CME credit is no longer available for this issue
CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue
HOW TO USE THIS CME ACTIVITY
CME credit is no longer available for this issue
This CME activity consists of a video component. The participant should watch the video.
CONTENT VALIDATION AND DISCLOSURES
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:
Nikhil C Munshi, MD
Associate Professor of Medicine, Harvard Medical School
Associate Director, Jerome Lipper Multiple Myeloma Center
Dana-Farber Cancer Institute
Boston, Massachusetts
Advisory Committee: Celgene Corporation, Millennium: The Takeda Oncology Company, Novartis Pharmaceuticals Corporation, Onyx Pharmaceuticals Inc; Consulting Agreements: Celgene Corporation, Millennium: The Takeda Oncology Company, Novartis Pharmaceuticals Corporation.
A Keith Stewart, MBChB
Dean for Research
Polak Professor of Cancer Research
Mayo Clinic in Arizona
Scottsdale, Arizona
Consulting Agreements: Celgene Corporation, Millennium: The Takeda Oncology Company, Novartis Pharmaceuticals Corporation, Onyx Pharmaceuticals Inc; Paid Research: Millennium: The Takeda Oncology Company.
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: Allos Therapeutics, Amgen Inc, AstraZeneca Pharmaceuticals LP, Aureon Laboratories Inc, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Cephalon Inc, Daiichi Sankyo Inc, Dendreon Corporation, Eisai Inc, EMD Serono Inc, Genentech BioOncology, Genomic Health Inc, ImClone Systems, a wholly owned subsidiary of Eli Lilly and Company, Lilly USA LLC, Millennium: The Takeda Oncology Company, Mundipharma International Limited, Myriad Genetics Inc, Novartis Pharmaceuticals Corporation, OSI Oncology, Sanofi and Seattle Genetics.
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 Celgene Corporation, Millennium: The Takeda Oncology Company and Onyx Pharmaceuticals Inc.
Hardware/Software Requirements:
An Internet connection that is at least 28.8 Kbps
A monitor set to 1280 x 1024 pixels or more
Internet Explorer 6.x or newer, Firefox 2.x or newer, or Safari 2.x or newer
Macromedia Flash plug-in 6.0 or greater
Adobe Acrobat Reader
(Optional) Sound card and speakers for audio
Last review date: July 2011
Expiration date: July 2012
Acknowledge and close
(WiFi is recommended for best performance):
Case 1: A 57-year-old man with hypertension, proteinuria and a creatinine of 2.5 found to have free kappa light chain deposition on renal biopsy and no bone disease
There is near-universal agreement that patients with myeloma and renal failure should receive a bortezomib-containing regimen up front, holding out on the use of an IMiD until or unless renal function improves. In this case the patient received CyBorD followed by an autotransplant, which resulted in a CR and normalization of the creatinine. Dr Stewart then took us through his rationale for recommending post-transplant lenalidomide, which the patient is now receiving. The reason he, Dr Munshi and many other investigators favor maintenance has a lot to do with one data set we spent a lot of time on: The just-reported (May) update of the Phase III CALGB trial of lenalidomide versus placebo as maintenance therapy after stem cell transplant. Although both investigators acknowledged that more secondary cancers (18 versus 4) were seen in this study and others, they were also in agreement that these risks are outweighed by the lesser number of progressions
Case 2: A 71-year-old man with high-risk t(4;14) myeloma
The older, nontransplant-eligible patient clearly represents a challenging clinical situation faced by many community oncologists, and it was very apropos that there was disagreement among the faculty. While Nikhil recommended against a melphalan-containing regimen in favor of dose-reduced “RVD light,” Keith, who also favors a three-drug approach, was quick to point out that Phase III randomized data have shown both MPV and MPT to prolong overall survival, whereas no such evidence exists for CyBorD or RVD. Interestingly, the patient, who was treated a number of years ago, received “Rd” as part of a clinical trial, which caused a significant tumor response but was gradually associated with increasing fatigue. Working closely with the patient, Keith was able to continue treatment at a reduced dose for 26 months.
This man also had extensive bone disease, which led to a discussion of the landmark MRC trial demonstrating a survival benefit for patients receiving zoledronic acid compared to clodronate. The faculty commented on follow-up data from the trial presented at ASCO demonstrating a reduction in bone events in patients initially presenting with and without bone disease. This large, well-conducted study design is not likely to be confirmed soon as no comparable trial is out there, but the faculty members and others are carefully reconsidering their duration of bisphosphonate use (indefinite in MRC) and treatment of patients without bone disease.
Case 3: A 62-year-old man with progression after thalidomide/dexamethasone followed by transplant, followed by lenalidomide (response → progression), followed by bortezomib/dexamethasone (response → peripheral neuropathy)
Having exhausted all available approved treatment options, this patient entered a clinical trial of the next-generation proteasome inhibitor carfilzomib and achieved a very good partial response with no neuropathy. The profound human benefits of treatment for this individual led to a thought-provoking conversation about the revolution in myeloma translational research that was so eloquently described at ASCO by Nikhil’s colleague Ken Anderson during his Karnofsky Award lecture. Echoing Dr Anderson’s talk, we touched on the complex biology of the proteasome and the specificity of carfilzomib binding. We also delved into other novel players in the field, including the encouraging work reported on the third-generation IMiD pomalidomide, which — like carfilzomib — is most noteworthy for the clear-cut objective responses observed in patients with disease progression on earlier-generation agents.
Join us tonight for an interdisciplinary discussion of targeted treatment, including anti-HER therapy, in a solid tumor that we have mainly associated with chemotherapy — gastric cancer — with faculty members Charles Fuchs, David Ilson and pathologist Laura Tang.