Accreditation/Credit Designation

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Takeda Oncology.

Advances In™ Multiple Myeloma: Using Proteasome Inhibitors Throughout the Disease Continuum

Release Date: December 23, 2019
Expiration Date: December 23, 2020
Media: Internet - based

Activity Overview

Therapeutic options in patients with multiple myeloma (MM) have expanded rapidly with enhanced understanding of tumor biology and of the heterogeneous nature of the disease; these include the clinical development of proteasome inhibitors (PIs). Several PIs are approved for the treatment of MM, and in addition to the currently approved agents, trials are ongoing for emerging PIs in the frontline, relapsed/refractory, and maintenance therapy settings. Different combination strategies that incorporate PIs are available as treatment options, and each is associated with different adverse-event profiles and considerations for tolerability. As new information accumulates, appropriate clinical application of PIs within the changing treatment landscape becomes increasingly more challenging.

This Advances in™ Multiple Myeloma program will help clinicians meet the challenge of acquiring this knowledge by featuring a series of video interviews with Sagar Lonial, MD, an expert on MM. He will highlight key characteristics that help differentiate among PIs that are approved for the frontline and relapsed/refractory treatment settings for MM, as well as among PIs that are under clinical development.

Benefits of Participating

  • Increase knowledge and competence in the best-practice use of PIs for patients with MM
  • Learn strategies to optimally manage treatment-related adverse events while treating patients with PI-based therapies
  • Build confidence in your knowledge of how to integrate patient and disease characteristics into the clinical decision-making process for the use of PI-based therapies
  • Improve knowledge of current clinical data on the use of PIs for the treatment of MM

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Takeda Oncology.

Instructions for This Activity and Receiving Credit

  • You will need to log in to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review video files/content until you finish the presentation.
  • At the end of the activity, “Educational Content/Videos” will be available for your reference.
  • In order to receive a CME Certificate, you must complete the activity.
  • Complete the Posttest and pass with a score of 70% or higher, complete the Evaluation, and then click on “Request for Credit.” You may immediately download a CME Certificate upon completion of these steps.

Target Audience

This educational program is directed toward medical oncologists and hematologists who treat patients with multiple myeloma. Fellows, nurses, nurse practitioners, physician assistants, and other healthcare professionals involved in the treatment of multiple myeloma will also be invited to participate in the activity.

Learning Objectives

Upon successful completion of this educational activity, you should be better prepared to:

  • Differentiate between proteasome inhibitor-based combination strategies for the treatment of MM.
  • Identify patient and disease characteristics that influence the choice of appropriate proteasome inhibitor treatment strategies for MM.
  • Formulate strategies to proactively identify and mitigate adverse events associated with proteasome inhibitors.
  • Evaluate emerging data regarding the use of proteasome inhibitors and combination strategies for the treatment of MM.

Faculty, Staff, and Planners’ Disclosures

Faculty

Sagar Lonial
Sagar Lonial, MD, FACP
Chief Medical Officer
Winship Cancer Institute of Emory University
Professor and Chair
Anne and Bernard Gray Family Chair in Cancer
Department of Hematology and Medical Oncology
Emory University School of Medicine
Emory University
Atlanta, GA

Disclosures: Grant Research Support: Celgene, Janssen, Takeda; Consultant: Celgene, Novartis, Bristol-Myers Squibb, Takeda, Janssen, GlaxoSmithKline, Amgen, AbbVie.

The staff of Physicians' Education Resource®, LLC (PER®) have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or the company that provided commercial support.

PER Pulse™ Recaps

1 of 3

This is a continuing medical education (CME)-certified activity in which Sagar Lonial, MD, FACP, an expert on multiple myeloma (MM), discusses the use of proteasome inhibitors (PIs) in the treatment of MM, highlighting approved PIs as well as those that are under clinical development. He will focus on the key characteristics that differentiate each PI to help clinicians make evidence-based treatment choices in daily practice and prepare them for developments that could change future best practice.

  • FDA-approved PIs for the treatment of MM include bortezomib, carfilzomib, and ixazomib. Specific indications vary by agent. Clinicians are encouraged to refer to the package inserts of each PI for details.1-3
    • Bortezomib is a reversible PI administered subcutaneously that is available in all phases.1 Dosage once or twice weekly on a schedule of 3 weeks on, 1 week off or 2 weeks on, 1 week off is offered in all phases. Peripheral neuropathy is most common with this PI.
    • Carfilzomib, an irreversible PI associated with limited peripheral neuropathy, has a wide range of dosages depending on the agent it is paired with; once-weekly dosing is optional.2 Toxicities include reversible symptoms associated with heart failure.
    • Ixazomib is the first PI to offer oral administration in the second-line setting and beyond.3 Doses begin at 4 mg orally on days 1, 8, and 15 every 28 days and are subsequently determined by the choice of partner agent; peripheral neuropathy is less frequent compared with bortezomib but GI adverse effects are more prominent.
  • Oprozomib and marizomib are two promising PIs under clinical investigation for the treatment of relapsed/refractory MM (RRMM).4,5

“The biggest difference amongst the approved PIs really has to do with reversible versus irreversible and some of that has to do with half-life and frequency of administration.”
—Sagar Lonial, MD, FACP

References

  1. Velcade [package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc. www.velcade.com/files/pdfs/velcade_prescribing_information.pdf. Updated April 2019. Accessed January 28, 2020.
  2. Kyprolis [package insert]. Thousand Oaks, CA: Amgen. www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/kyprolis/kyprolis_pi.ashx. Updated October 2019. Accessed January 28, 2020.
  3. Ixazomib [package insert]. Cambridge, MA: Takeda Pharmaceutical Company Limited. www.ninlarohcp.com/pdf/prescribing-information.pdf. Updated November 2016. Accessed January 28, 2020.
  4. Hari P, Matous JV, Voorhees PM, et al. Oprozomib in patients with newly diagnosed multiple myeloma. Blood Cancer J. 2019;9(9):66. doi: 10.1038/s41408-019-0232-6.
  5. Potts BC, Albitar MX, Anderson KC, et al. Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011;11(3):254-284. doi: 10.2174/156800911794519716.

2 of 3

This is a continuing medical education (CME)-certified activity in which Sagar Lonial, MD, FACP, an expert on multiple myeloma (MM), discusses the use of proteasome inhibitors (PIs) in the treatment of MM, highlighting approved PIs as well as those that are under clinical development. He will focus on the key characteristics that differentiate each PI to help clinicians make evidence-based treatment choices in daily practice and prepare them for developments that could change future best practice.

  • The TOURMALINE-MM1 trial (NCT01564537) is a phase III study comparing the efficacy of ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed/refractory MM (RRMM).1
    • Patients who received ixazomib, an oral and reversible PI, demonstrated significantly longer progression-free survival with minimal toxicity.1 Lonial discusses how this trial shapes views on maintenance therapy selection as well as duration of therapy.
  • The phase III ENDEAVOR trial (NCT01568866) compared the efficacy and safety of carfilzomib and dexamethasone with that of bortezomib and dexamethasone in patients with RRMM.
    • Carfilzomib is an irreversible PI administered intravenously either once or twice weekly in combination with dexamethasone or with lenalidomide and dexamethasone. Data from this report support the option of carfilzomib in the treatment of RRMM.

“I think what we know about the use of proteasome inhibitor-based therapy, in the context of relapsed/refractory MM, is that combinations are clearly better.”
—Sagar Lonial, MD, FACP

References

  1. Moreau P, Masszi T, Grzasko N, et al; TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621-1634. doi: 10.1056/NEJMoa1516282.
  2. Ixazomib [package insert]. Cambridge, MA: Takeda Pharmaceutical Company Limited. www.ninlarohcp.com/pdf/prescribing-information.pdf. Updated November 2016. Accessed January 28, 2020.
  3. Dimopoulos MA, Moreau P, Palumbo A, et al; ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study [published online December 5, 2015]. Lancet Oncol. 2016;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7.
  4. Kyprolis [package insert]. Thousand Oaks, CA: Amgen. www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/kyprolis/kyprolis_pi.ashx. Updated October 2019. Accessed January 28, 2020.

3 of 3

This is a continuing medical education (CME)-certified activity in which Sagar Lonial, MD, FACP, an expert on multiple myeloma (MM), discusses the use of proteasome inhibitors (PIs) in the treatment of MM, highlighting approved PIs as well as those that are under clinical development. He will focus on the key characteristics that differentiate each PI to help clinicians make evidence-based treatment choices in daily practice and prepare them for developments that could change future best practice.

  • PI-related toxicity is drug specific due to differing mechanisms. The following are summaries of the most notable toxicities of individual PIs.
    • Bortezomib: peripheral neuropathy; ixazomib: GI disturbances; carfilzomib: infusion reactions, heart failure-like symptoms, pulmonary complications; marizomib: reversible CNS toxicity (hallucinations, loss of coordination); general class toxicity: hematologic (platelet reductions)
  • Treatment of PI-related toxicity
    • Patient education and awareness are key; prevention is preferred over treatment. Treatments may include dose reductions, drug discontinuation, the use of steroids, and the restriction of fluid intake. Mitigation strategies will depend on the PI used, the severity of toxicity, and patient status.

“One of the keys to dealing with adverse events is preventing them. So, letting patients know early on [that] if [they’re] beginning to have these [adverse] effects [they should] let us know, so we can hold doses or reduce doses, [is important].”
—Sagar Lonial, MD, FACP

References

  1. Merin NM, Kelly KR. Clinical use of proteasome inhibitors in the treatment of multiple myeloma. Pharmaceuticals (Basel). 2014;8(1):1-20. doi: 10.3390/ph8010001.
  2. Thibaudeau TA, Smith DM. A practical review of proteasome pharmacology. Pharmacol Rev. 2019:71(2):170-197. doi: 10.1124/pr.117.015370.

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