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Expert Interviews
Myeloma, Haematological Malignancies CE/CME accredited

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Experts answer questions with in-depth advice on the current clinical landscape and how new therapies and guidance might impact regional clinical practice. Useful tips below will show how to navigate the activity. Close

The rationale for protein degradation and immunomodulation in RRMM: Highlighting the latest data and available clinical trials

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Prof. Cristina Gasparetto is director of the Multiple Myeloma Program at Duke Health, Durham, NC, USA, which she was responsible for developing. The programme brings together a multidisciplinary team to manage all aspects of patient care, from diagnosis through all phases of management. Prof. Gasparetto is also professor of medicine at the Duke University School of Medicine. read more

Prof. Gasparetto’s research is focused on clinical translational research in multiple myeloma and other plasma cell disorders. She has led numerous studies in both the transplant and non-transplant settings, and she has co-authored numerous investigations on new target therapies in myeloma as well as novel approaches for transplantation.

During Prof. Gasparetto’s career she has been invited as a member of numerous national and international plasma cell dyscrasias committees, such as the Center for International Blood and Bone Marrow Transplant Research (CIBMTR), the National Comprehensive Cancer Network (NCCN) guidelines, Alliance/Cancer and Leukemia Group B (CALGB) myeloma executive committee, the Clinical Trials Network (CTN), the International Myeloma Working Group (IMWG), and the ‘Connect Registry’.

Prof. Cristina Gasparetto discloses: Consultancy fees from Amgen, BMS and GSK. Speaker’s bureau fees from Karyopharm and Sanofi.

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Prof. Sagar Lonial is chief medical officer of the Winship Cancer Institute at Emory University and professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta, GA, USA. read more

Prof. Lonial’s current research is focused on combinations of novel agents as therapy for myeloma.

Prof. Lonial serves as vice chair of the Myeloma Committee in the Eastern Cooperative Oncology Group (ECOG) and as myeloma editor for Clinical Lymphoma, Myeloma & Leukemia. He has received the Celgene Young Investigator Award, Indo American Cancer Association (IACA) Lifetime Achievement Award, the COMy Multiple Myeloma Excellence Award for Clinical Science and the Giants of Cancer Care inductee.

Prof. Sagar Lonial discloses: Advisory board and consultancy fees from Abbvie, Amgen, BMS, Celgene, Genentech, GSK, Janssen, Novartis, Pfizer and Regeneron. Grants/research support from BMS, Janssen and Novartis. Stock/shareholder (self-managed) in TG Therapeutics.

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Prof. Sundar Jagannath is director of the multiple myeloma programme at the Tisch Cancer Institute and a professor of medicine, haematology and medical oncology at the Icahn School of Medicine at Mount Sinai and Mount Sinai Chair for Multiple Myeloma in New York, NY, USA. read more

Prof. Jagannath and his team treat a high volume of patients, including more than 400 new patients each year, providing novel, precision medicine therapies.

Prof. Jagannath has published more than 180 peer-reviewed articles and presented more than 150 abstracts. He is editor-in-chief of Clinical Lymphoma, Myeloma & Leukemia and a board member for the Society of Hematologic Oncology. Prof. Jagannath has received multiple awards, including the Innovator Award from the Multiple Myeloma Research Consortium (MMRC) and the Michaeli Lifetime Achievement Award for Outstanding Contributions to Multiple Myeloma from the SASS-ARENA Foundation for Medical Research.

Prof. Sundar Jagannath discloses: Advisory board or panel fees from BMS and Janssen. Consultancy fees from BMS, Caribou, Janssen, Karyopharm, Legend Biotech, Regeneron, Sanofi and Takeda.

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Learning Objectives

After watching this activity, participants should be better able to:

  • Recognize the unmet needs in patients with relapsed/refractory multiple myeloma
  • Outline the rationale for therapies based on protein degradation and immunomodulation for the treatment of patients with relapsed/refractory multiple myeloma
  • Evaluate the latest evidence for therapies based on protein degradation and immunomodulation for relapsed/refractory multiple myeloma and arrange for appropriate patients to be referred to available clinical trials
Overview

In this activity, three internationally renowned multiple myeloma experts share insights into the unmet treatment needs for patients with relapsed/refractory multiple myeloma, the rationale for emerging protein degradation and immunomodulation-based therapies, and the latest data and ongoing clinical trials for these investigational agents.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of haematologists, oncologists and haemato-oncologists involved in the management of multiple myeloma.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Prof. Cristina Gasparetto discloses: Consultancy fees from Amgen, BMS and GSK. Speaker’s bureau fees from Karyopharm and Sanofi.

Prof. Sagar Lonial discloses: Advisory board and consultancy fees from Abbvie, Amgen, BMS, Celgene, Genentech, GSK, Janssen, Novartis, Pfizer and Regeneron. Grants/research support from BMS, Janssen and Novartis. Stock/shareholder (self-managed) in TG Therapeutics.

Prof. Sundar Jagannath discloses: Advisory board or panel fees from BMS and Janssen. Consultancy fees from BMS, Caribou, Janssen, Karyopharm, Legend Biotech, Regeneron, Sanofi and Takeda.

Content Reviewer

Carolina Leon BSN, MSN, ARNP-BC has no relevant financial relationships to disclose.

Touch Medical Contributor

Hannah Fisher has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 15 February 2024. Date credits expire: 15 February 2025.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

This activity is CE/CME accredited

To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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Topics covered in this activity

Myeloma / Haematological Malignancies
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touchEXPERT OPINIONS
The rationale for protein degradation and immunomodulation in RRMM: Highlighting the latest data and available clinical trials
0.75 CE/CME credit

Question 1/5
Your patient with multiple myeloma is refractory to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. Based on real-world data from the LocoMMotion study, how would you counsel your patient about their expected survival?

CD, cluster of differentiation.

In LocoMMotion, a real-world, prospective, non-interventional, multinational study, the median overall survival in patients who were triple-class refractory at baseline treated with standard of care (n=183) was 11.1 months.

Reference
Mateos M-V, et al. Leukemia. 2022;36:1371–6.

Question 2/5
What is the rationale for targeting cereblon in the treatment of relapsed/refractory multiple myeloma?

Cereblon forms part of the functional E3 ubiquitin ligase complex and functions as a substrate receptor that targets proteins for degradation through the ubiquitin-proteasome system.1 Neosubstrates of cereblon include Ikaros and Aiolos, which are members of the B-cell transcription factors family critical for plasma cell development and proliferation, and activation of the immune system.1,2 Ikaros and Aiolos sustain multiple myeloma growth and survival,3 and their degradation leads to growth inhibition and cell death.4

References

  1. Shi Q, Chen L. J Immunol Res. 2017;2017:9130608.
  2. Huang PA, et al. Sci Rep. 2019;9:14884.
  3. Cippitelli M, et al. Int J Mol Sci. 2021;22:1103.
  4. Bird S, Pawlyn C. Blood. 2023;142:131–40.
Question 3/5
Which of the following characteristics of cereblon E3 ligase modulators may support their future use in frail/elderly patients?

The cereblon E3 ligase modulators iberdomide and mezigdomide are administered orally.1,2 Oral regimens may be beneficial for frail/elderly patients where convenience may be a priority or they have limited access to specialized hospitals.1,2

References

  1. Lonial S, et al. Lancet Haematol. 2022;9:e822–32.
  2. Richardson PG, et al. N Engl J Med. 2023;389:1009–22.
Question 4/5
In the phase II dose-expansion cohort of the CC-220-MM-001 trial of iberdomide + dexamethasone in patients with relapsed/refractory multiple myeloma, in what range was the reported overall response rate?

The overall response rate was reported as 26% in 107 patients who received iberdomide + dexamethasone. 

Reference

Lonial S, et al. Lancet Haematol. 2022;9:e822–32.

Question 5/5
Based on the key inclusion criteria, which of the following patients would you consider for referral to the SUCCESSOR-2 trial, a phase III trial comparing mezigdomide, carfilzomib and dexamethasone to carfilzomib and dexamethasone?

CD, cluster of differentiation; MM, multiple myeloma; RRMM, relapsed/refractory multiple myeloma.

The SUCCESSOR-2 trial is a phase III, randomized, multicentre, open-label trial comparing mezigdomide, carfilzomib and dexamethasone to carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma and measurable disease. Participants must have:

  • Received at least one prior line of anti-myeloma therapy
  • Received prior treatment with lenalidomide and at least two cycles of an anti-CD38 monoclonal antibody 
  • Achieved minimal response or better to at least one prior anti-myeloma therapy
  • Documented disease progression during or after their last anti-myeloma regimen

Abbreviation

CD, cluster of differentiation.

Reference

ClinicalTrials.gov. NCT05552976. Available at: https://clinicaltrials.gov/study/NCT05552976 (accessed 10 January 2024).

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