RVD in Patients with High-Risk, Relapsed/Refractory Multiple

Myeloma

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CME INFORMATION

OVERVIEW OF ACTIVITY

Each year, thousands of clinicians and basic scientists sojourn to the American Society of Clinical Oncology (ASCO) Annual Meeting to learn about recent clinical advances that yield alterations in state-of-the-art management for all tumor types. Attracting more than 30,000 attendees from every corner of the globe to both unveil and digest the latest research, ASCO is unmatched in attendance and clinical relevance. Results presented from ongoing trials lead to the emergence of new therapeutic agents and changes in the indications for existing treatments across all cancer medicine. Despite the importance of the conference, the demands of routine practice often limit the amount of time oncology clinicians can realistically dedicate to travel and learning. To bridge the gap between research and patient care, this CME activity will deliver a serial review of the key presentations from the ASCO Annual Meeting and expert perspectives on how these new evidence-based concepts can be applied to routine clinical care. This activity will assist medical oncologists and other cancer clinicians in the formulation of optimal clinical management strategies for patients with diverse forms of cancer.

LEARNING OBJECTIVE

• Consider the role of RVD in patients with relapsed/refractory MM who were previously treated with lenalidomide, bortezomib, thalidomide and/or transplantation.

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Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT

Research To Practice designates this educational activity for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

HOW TO USE THIS CME ACTIVITY

This CME activity contains slides and edited commentary. To receive credit, the participant should review the slide presentation, read the edited commentary and complete the Educational Assessment and Credit Form located at CME.ResearchToPractice.com.

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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:

Paul G Richardson, MD Associate Professor of Medicine Harvard Medical School Clinical Director of the Jerome Lipper Center for Multiple Myeloma Dana-Farber Cancer Institute Boston, Massachusetts

Advisory Committee and Speakers Bureau: Celgene Corporation, Millennium Pharmaceuticals Inc.

EDITOR — Neil Love: 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: Abraxis BioScience, AstraZeneca Pharmaceuticals LP, Aureon Laboratories Inc, Bayer Pharmaceuticals Corporation/Onyx Pharmaceuticals Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Centocor Ortho Biotech Services LLC, Cephalon Inc, Eisai Inc, Eli Lilly and Company, EMD Serono Inc, Genentech BioOncology, Genomic Health Inc, Genzyme Corporation, GlaxoSmithKline, ImClone Systems Incorporated, Merck and Company Inc, Millennium Pharmaceuticals Inc, Novartis Pharmaceuticals Corporation, OSI Oncology, Roche Laboratories Inc, Sanofi-Aventis and Wyeth.

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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 program is supported by educational grants from Celgene Corporation, Eli Lilly and Company, Genomic Health Inc, GlaxoSmithKline and Millennium Pharmaceuticals Inc.

Last review date: July 2009 Expiration date: July 2010

Click here to go directly to our slides on Palumbo’s VMPT presentation and Richardson’s RVD poster.

Corey Langer likes to mirthfully refer to his lung cancer clinical investigator colleagues as the “pulmonary cognoscenti,” but what many tumor site-specific specialists don’t appreciate is the challenge faced by practicing medical oncologists in keeping up with the recent explosions of pathways, assays and new molecular-targeted therapies in almost every corner of current cancer medicine.

At the December 2007 ASH meeting, multiple myeloma instantly became one of those areas when a series of Phase III trials and one landmark Phase I-II study changed everything in the disease. The theme of the Phase III work was the remarkable efficacy of a new generation of regimens featuring an IMiD® (particularly lenalidomide) and/or a proteasome inhibitor (bortezomib) while the Phase I-II study was based on the oldest principle in oncology, combining the best agents available in an attempt to deliver a first or second round knockdown.

While ASH continues to be the premier setting for new Heme-Onc and myeloma data sets, ASCO 2009 included two papers that merit particular attention: an Italian alphabet study (VMP versus VMPT) by Palumbo et al that, according to discussant Vincent Rajkumar, was “practice changing,” and another data set from the Dana-Farber group on a regimen that is difficult not to get excited about — RVD or VRD (lenalidomide, bortezomib and dexamethasone), perhaps the new TAC or AC T of myeloma.

Even super busy oncologists in practice need to know about the dramatic reduction in peripheral neuropathy observed when the Italians used weekly rather than twice weekly bortezomib, and the demonstration that RVD not only results in unprecedented outcomes as up-front therapy, but also in relapsed disease, including patients who previously received either an IMiD or bortezomib.

Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Research To Practice designates each educational activity for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

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See our slides and commentary on Palumbo’s VMPT presentation and Richardson’s RVD poster, and watch out for our next 5-Minute Journal Club that focuses on exciting ASCO papers on a new and older antibody: ofatumumab in CLL and trastuzumab in...gastric cancer (not a typo, folks).

Neil Love, MD Research To Practice Miami, Florida

RVD in Patients with High-Risk, Relapsed/Refractory Multiple MyelomaPresentation discussed in this issue:

Anderson KC et al. A phase II study of RVD in patients with relapsed/refractory MM. ASCO 2009;Abstract 8536.

Slides from the presentation and excerpts from a related CME symposium (May 31, 2009) featuring Paul G Richardson, MD

DR RICHARDSON: What we are seeing with our myeloma therapies is that staying on treatment matters, and therefore, the tolerability of a regimen becomes additionally important. With RVD, less is more and what was striking was both the quality of responses and a remarkably favorable toxicology with a low rate of significant neuropathy and thromboembolic complications. Also, importantly, response rates were equivalent in all risk groups.

It’s also interesting that when you add drugs to RVD — for example, cyclophosphamide in data from Shaji Kumar and the Mayo Group — high quality and depth of response is observed. The EVOLUTION trial is ongoing, and compares RVD to CRVD.

DR LOVE: What about the RVD compared to either bortezomib/dex or one of the IMiDs/dex?

DR RICHARDSON: I think that’s what’s been impressive, Neil. When you combine the three drugs, you can use less of each to achieve more. The neuropathy signal with RVD is less than you would expect, which was intriguing and has a number of theoretical explanations.

Having said that, other aspects of RVD toxicology are favorable. The rates of deep vein thrombosis are low with aspirin as prophylaxis, and we found that this is not a regimen simply for younger patients. In our trial, the oldest patient is from my practice. He recently celebrated his 86th birthday, had 12 months of treatment and is now on lenalidomide maintenance with a VGPR and excellent performance status.

Dr Richardson is Associate Professor of Medicine at Harvard Medical School as well as the Clinical Director of the Jerome Lipper Center for Multiple Myeloma at Dana-Farber Cancer Institute in Boston, Massachusetts.